Neurology_Adams

Neurology_Adams. Here the source of the pain is usually in a bodily organ and is caused by a lesion that irritates and destroys nerve endings. Consequently, the term nociceptive pain is often used even though it is ambiguous. It usually means an involvement of structures bearing the origin of pain fibers. Cancer is the most frequent example. Osseous metastases, tumors of the kidney, pancreas, or liver, peritoneal tumor implants, invasion of retroperitoneal tissues or the hilum of the lung, and infiltration of nerves of the brachial or lumbosacral plexuses can be extremely painful, and the origin of the pain may remain obscure for a long time. Sometimes it is necessary to repeat all diagnostic procedures after an interval of a few months, even though at first they were negative. From experience one learns to be cautious about reaching a diagnosis from insufficient data. Treatment in the meantime is directed to the relief of pain, at the same time instilling in the patient a need to cooperate with a


Neurology_Adams

Neurology_Adams. to be cautious about reaching a diagnosis from insufficient data. Treatment in the meantime is directed to the relief of pain, at the same time instilling in the patient a need to cooperate with a program of expectant observation.


Neurology_Adams

Neurology_Adams. These terms are sometimes used interchangeably to designate pain that arises from direct stimulation of nervous tissue itself, central or peripheral, exclusive of pain as a consequence of stimulation of C fibers by lesions of other bodily structures (i.e., the nociceptive pain described above). The term “neuropathic” has been attached more often to pain arising in the peripheral nervous system. This category comprises a variety of disorders involving single and multiple nerves, notably trigeminal neuralgia and those caused by herpes zoster, diabetes, and trauma; neuromas and neurofibromas, polyneuropathies of diverse type; root irritation from a prolapsed disc; and spinal arachnoiditis. Neurogenic pain of central origin includes the thalamic pain syndrome of Dejerine-Roussy and spinal cord injuries; and parietal lobe infarction such as the cases described by Schmahmann and Leifer. As a rule, lesions of the cerebral cortex and white matter are associated not with pain but with


Neurology_Adams

Neurology_Adams. cord injuries; and parietal lobe infarction such as the cases described by Schmahmann and Leifer. As a rule, lesions of the cerebral cortex and white matter are associated not with pain but with hypalgesia. Schott (1996) has reviewed the clinical features that characterize central pain. Particular diseases giving rise to neuropathic pain are considered in their appropriate chapters but the following remarks are applicable to the entire group.


Neurology_Adams

Neurology_Adams. The sensations that characterize neuropathic pain vary and are often multiple—burning, gnawing, aching, and shooting or lancinating qualities are described. There is a frequent association with the symptoms of hyperesthesia, hyperalgesia, allodynia, or hyperpathia. The abnormal sensations coexist in many cases with a sensory deficit and local autonomic dysfunction. Furthermore, chronic pain of neuropathic injury generally responds less well to treatment in comparison to acute pain. The following are the main types of neurogenic pain.


Neurology_Adams

Neurology_Adams. Pain states of peripheral nerve origin, for which the term neuropathic is more strictly applicable, far outnumber those caused by spinal cord, brainstem, thalamic, and cerebral disease. Although the pain is localized to a sensory territory supplied by a nerve, plexus or nerve root, it often radiates to adjacent areas. Sometimes the onset of pain acuity follows an injury; more often it appears at some point during the evolution or recession of the disorder. The disease of the nerve may be obvious, expressed by the usual sensory, motor, reflex, and autonomic changes, or these changes may be undetectable by standard tests. In the latter case, the term neuralgia is used.


Neurology_Adams

Neurology_Adams. The postulated mechanisms of peripheral nerve pain are diverse and differ from those of central diseases. Some of the major ideas were mentioned in the earlier section on chronic pain. One mechanism is denervation hypersensitivity, first described by Walter Cannon. He noted that when a group of neurons is deprived of its natural innervation, they become hyperactive. Others point to a reduced density of certain types of fibers in nerves supplying a causalgic zone as the basis of the burning pain but the comparison of the density of nerves from painful and nonpainful neuropathies has not proved to be consistently different. For example, Dyck and colleagues, in a study of painful versus nonpainful axonal neuropathies, concluded that there was no difference between them in terms of the type of fiber degeneration. Also, the occurrence of ectopic impulse generation all along the surface of injured axons and the possibility of ephaptic activation of unsheathed axons seem applicable


Neurology_Adams

Neurology_Adams. type of fiber degeneration. Also, the occurrence of ectopic impulse generation all along the surface of injured axons and the possibility of ephaptic activation of unsheathed axons seem applicable particularly to some causalgic states. Stimulation of the nervi nervorum of larger nerves by an expanding intraneural lesion or a vascular change was postulated by Asbury and Fields as the mechanism of nerve trunk pain. The sprouting of adrenergic sympathetic axons in response to nerve injury has already been mentioned and is an ostensible explanation for the abolition of some cases of causalgic pain by sympathetic blockade. This has given rise to the term sympathetically sustained pain for some cases of causalgia, as discussed below.


Neurology_Adams

Neurology_Adams. Regenerating axonal sprouts, as in a neuroma, are also hypersensitive to mechanical stimuli. On a molecular level, it has been shown that voltage-gated sodium channels accumulate at the site of a neuroma and all along the axon after nerve injury, and that this gives rise to ectopic and spontaneous activity of the sensory nerve cell and its axon. Such firing has been demonstrated in humans after nerve injury. This mechanism is concordant with the relief of neurogenic pain by sodium channel-blocking antiepileptic drugs. Spontaneous activity in nociceptive C fibers is thought to give rise to burning pain; firing of large myelinated A fibers is believed to produce dysesthetic pain induced by tactile stimuli. The abnormal response to stimulation is also influenced by sensitization of central pain pathways, probably in the dorsal horns of the spinal cord, as outlined in the review by Woolf and Mannion. Hyperalgesia and allodynia are thought to result from such a spinal cord mechanism.


Neurology_Adams

Neurology_Adams. pain pathways, probably in the dorsal horns of the spinal cord, as outlined in the review by Woolf and Mannion. Hyperalgesia and allodynia are thought to result from such a spinal cord mechanism. Several observations have been made regarding the neurochemical mechanisms that might underlie these changes but none provides a consistent explanation. Possibly more than one of these mechanisms is operative in a given peripheral nerve disease.


Neurology_Adams

Neurology_Adams. Evidence that the sodium channel can generate neural pain is given by the extraordinary disease “paroxysmal extreme pain disorder” also known as “familial rectal pain syndrome.” Here, a mutation of the sodium channel gene, SCN9A, leads to the early onset of paroxysmal autonomic changes and attacks of excruciating deep burning pain in the rectum, eye, or jaw, or diffusely, as described by


Neurology_Adams

Neurology_Adams. Fertleman and coworkers. Similar but more diffuse painful states such as erythromelalgia and other pain disorders are being uncovered that are predicated on voltage-gated sodium channel mutations and more impressively, by the congenital absence of the ability to experience pain due to a loss of function mutation in a sodium channel gene and a mutation in the tyrosine kinase receptor gene. Fischer and Waxman provide a summary of the mutations in the sodium channel gene and their clinical presentations. Potassium channels have also been implicated in cases of severe pain, with IgG found against various components of voltage gated potassium channels (VGKC) in a series of patients with idiopathic pain often accompanied by hyperhidrosis described by Klein and colleagues. They suggested that immune suppression and antiepileptic drugs were helpful but these proposals require corroboration.


Neurology_Adams

Neurology_Adams. Causalgia is the name that Weir Mitchell applied to a rare (except in time of war) type of peripheral neuralgia consequent upon trauma, with partial interruption of the median or ulnar nerve and, less often, the sciatic or peroneal nerve (see also “Chronic Pain” further on and discussion in Chap. 43, Diseases of the Peripheral Nerves). It is characterized by persistent, severe pain in the hand or foot, most pronounced in the digits, palm of the hand, or sole. The pain has a burning quality and frequently radiates beyond the territory of any peripheral nerve. The painful parts are exquisitely sensitive to contact, so the patient cannot bear the pressure of clothing or drafts of air; even ambient heat, cold, noise, or emotional stimuli intensify the causalgic symptoms. The affected extremity is kept protected and immobile, often wrapped in a cloth moistened with cool water. Sudomotor, vasomotor, and, later, trophic abnormalities are usual accompaniments of the pain.


Neurology_Adams

Neurology_Adams. The term reflex sympathetic dystrophy (RSD) has been used to encompass several additional aspects of sustained pain after limb injury in the absence of evident damage to adjacent nerves. The current nomenclature for this syndrome is complex regional pain syndrome type 1 (CRPS I) but a plethora of terms (e.g., Sudeck atrophy of bone, minor causalgia, shoulder–hand syndrome, algodystrophy, or algoneurodystrophy) have also been used. It may also follow nontraumatic lesions of the peripheral nerves or even lesions of the CNS (“mimocausalgia”). The additional features, beyond the pain, are thinning of skin, warm surface temperature, poor nail growth, thinning of underlying bone and general disruption of thermal and vascular control. The skin of the affected part is moist and warm or cool and soon becomes shiny and smooth, at times scaly, devoid of hair, and discolored. Complex regional pain syndrome type 2 (CPRS 2), which is also referred to as causalgia, represents the same syndrome


Neurology_Adams

Neurology_Adams. and soon becomes shiny and smooth, at times scaly, devoid of hair, and discolored. Complex regional pain syndrome type 2 (CPRS 2), which is also referred to as causalgia, represents the same syndrome except that a history of direct injury to a peripheral nerve can be identified.


Neurology_Adams

Neurology_Adams. A number of theories have been proposed to explain these regional pain syndromes. For many years they were attributed to a short-circuiting of impulses (ephaptic transmission), the result of an artificial connection between efferent sympathetic and somatic afferent pain fibers at the point of the nerve injury. The demonstration that causalgic pain could be abolished by depletion of neurotransmitters at sympathetic adrenergic endings shifted the presumed site of sympathetic-afferent interaction to the nerve terminals and suggested that the abnormal cross-excitation is chemical rather than electrical in nature. Another possible explanation is that an abnormal adrenergic sensitivity develops in injured nociceptors and that circulating or locally secreted sympathetic neurotransmitters trigger the painful afferent activity. Yet another theory holds that a sustained period of bombardment by sensory pain impulses from one region results in the sensitization of central sensory structures.


Neurology_Adams

Neurology_Adams. the painful afferent activity. Yet another theory holds that a sustained period of bombardment by sensory pain impulses from one region results in the sensitization of central sensory structures. Causalgia of this type can respond favorably, if only temporarily, to procaine block of the appropriate sympathetic ganglia and, for a longer time, to regional sympathectomy. Prolonged cooling and the intravenous injection of guanethidine, a sympathetic-blocking drug, into the affected limb (with the venous return blocked for several minutes) may alleviate the pain for days or longer. Epidural infusions, particularly of analgesics or ketamine, intravenous infusion of bisphosphonates, and spinal cord stimulators and intrathecal compounds are other forms of treatment, none entirely satisfactorily or for long duration (see Kemler et al). The roles of the central and sympathetic nervous systems in causalgic pain have been critically reviewed by Schott (1986, 2001) and by Schwartzman and McLellan.


Neurology_Adams

Neurology_Adams. for long duration (see Kemler et al). The roles of the central and sympathetic nervous systems in causalgic pain have been critically reviewed by Schott (1986, 2001) and by Schwartzman and McLellan. The reader may be aware of the similarities between these explanations and the ones proposed for all forms of chronic pain, discussed earlier.


Neurology_Adams

Neurology_Adams. Recent investigations have begun to define the molecular changes that occur in sensory neurons and the spinal cord in cases of chronic pain of this type. Alterations in N-methyl-d-aspartate (NMDA) receptors, induction of cyclooxygenase and prostaglandin synthesis, and changes in gabanergic inhibition in the dorsal horns have all been implicated (Woolf).


Neurology_Adams

Neurology_Adams. We have no explanation for the so-called causalgia–dystonia syndrome (Bhatia et al) in which a fixed dystonic posture is engrafted on a site of causalgic pain. The clinical features of both the causalgic and dystonic elements of the syndrome have been somewhat unusual in the cases reported. The degree of injury was often trivial or nonexistent and no signs of a neuropathic lesion were evident. Remarkably, both the causalgia and dystonia spread from their initial sites to widely disparate parts of the limbs and body. The syndrome has not responded consistently to any form of treatment, although some patients recovered spontaneously. Another interesting type of causalgia and reflex sympathetic dystrophy follows deep venous thrombosis in a leg and had in the literature been recorded as “algodystrophy.” It may be similar to the left shoulder and hand changes that come on months after a myocardial infarction (“shoulder–hand syndrome”).


Neurology_Adams

Neurology_Adams. The treatment of reflex sympathetic dystrophy is largely unsatisfactory, although a certain degree of improvement can be expected if treatment is started early and the limb is mobilized. The options for treatment are discussed further on.


Neurology_Adams

Neurology_Adams. There are several configurations of central lesions that damage the sensory system and produce severe pain. Deafferentation of secondary neurons in the posterior horns or of sensory ganglion cells that terminate on them may cause the deafferented cells to become continuously active and, if stimulated by a microelectrode, to reproduce pain. In the patient whose spinal cord has been transected, there may be intolerable pain in regions below the level of the lesion. It may be exacerbated or provoked by movement, fatigue, or emotion and projected to areas disconnected from suprasegmental structures (akin to the phantom pain in the missing part of an amputated limb). Here, and in the rare cases of intractable pain with lateral medullary or pontine lesions, loss of the descending inhibitory systems seems a likely explanation. This may also explain the pain of the Dejerine-Roussy thalamic syndrome described in the next chapter. Altered sensitivity and hyperactivity of central neurons are


Neurology_Adams

Neurology_Adams. systems seems a likely explanation. This may also explain the pain of the Dejerine-Roussy thalamic syndrome described in the next chapter. Altered sensitivity and hyperactivity of central neurons are alternative possibilities.


Neurology_Adams

Neurology_Adams. Further details concerning the subject of neuropathic pain can be found in the older but still informative writings of Scadding and of Woolf and Mannion.


Neurology_Adams

Neurology_Adams. It is not unusual for patients with depression to have pain as a dominant symptom. As emphasized previously, most patients with chronic pain of all types are depressed. Wells and colleagues, in a survey of a large number of depressed and chronic pain patients, have corroborated this clinical impression. Fields (1991) has elaborated a theoretical explanation of the overlap of pain and depression. In such cases, one is faced with an extremely difficult clinical problem— that of determining whether a depressive state is primary or secondary. Complaints of weakness and fatigue, depression, anxiety, insomnia, nervousness, irritability, palpitations, etc., are woven into the clinical syndrome, attesting to the prominence of a psychiatric disorder. In some instances the diagnostic criteria for depression cited in Chap. 48 provide some insight, but in others it is impossible to make this determination and may not be necessary as depression and pain are so often coincident. Empiric treatment


Neurology_Adams

Neurology_Adams. depression cited in Chap. 48 provide some insight, but in others it is impossible to make this determination and may not be necessary as depression and pain are so often coincident. Empiric treatment with antidepressant medication or, failing this, with electroconvulsive therapy is one way out of the dilemma.


Neurology_Adams

Neurology_Adams. Intractable pain may also be the leading symptom of both somatization and conversion reactions. Experienced physicians are familiar with the patient who has undergone multiple surgical procedures to address painful complaints (Briquet disease). The recognition and management of this group of disorders are discussed in Chap. 47.


Neurology_Adams

Neurology_Adams. The desire for compensation (e.g., workman’s compensation, disability status) is usually colored by persistent complaints of headaches, neck pain (whiplash injuries), low back pain, and other painful conditions. The question of ruptured disc is often raised, and laminectomy and spinal fusion may be performed (sometimes more than once) on the basis of dubious radiologic findings. Long delay in the settlement of litigation, allegedly to determine the seriousness of the injury, only enhances the symptoms and prolongs the disability. The medical and legal professions have no certain approach to such problems and often work at cross-purposes. We have found that a frank, objective appraisal of the injury, an assessment of any psychiatric problem, and encouragement to settle the legal claims as quickly as possible work in the best interests of all concerned. Although hypersuggestibility and relief of pain by placebos may reinforce the physician’s belief that there is a prominent factor of


Neurology_Adams

Neurology_Adams. quickly as possible work in the best interests of all concerned. Although hypersuggestibility and relief of pain by placebos may reinforce the physician’s belief that there is a prominent factor of hysteria or malingering (see Chap. 47), such data are difficult to interpret.


Neurology_Adams

Neurology_Adams. The possibility of drug addiction as a motivation for visiting the physician and reporting severe pain should be addressed. It is impossible to assess pain in addicted individuals, for their complaints are embedded into their need for medication. Temperament and mood should be evaluated carefully; the physician must remember that the depressed patient often denies feeling dysphoric and may even occasionally smile. The use of alcohol to self-medicate for pain usually indicates a depressive illness or lifelong alcohol dependence. When no medical, neurologic, or psychiatric disease can be established, one may be resigned to managing the painful state by the use of nonnarcotic medications and periodic clinical reevaluations. Such a course, though not altogether satisfactory, is preferable to prescribing excessive opioids or subjecting the patient to unnecessary surgery. Chronic Pain of Indeterminate Cause


Neurology_Adams

Neurology_Adams. Chronic Pain of Indeterminate Cause Pain in the thorax, abdomen, flank, back, face, head, or other part that cannot be traced to any visceral abnormality can create challenging clinical problems. In most cases, obscure neurologic sources, such as a spinal cord tumor and neuroma, have been excluded by repeated examinations and imaging procedures. A psychiatric disorder to which the patient’s symptoms and behavior might be attributed cannot be discerned. Yet the patient complains continuously of pain, is disabled, and spends a great deal of effort and resources seeking medical aid. In such a circumstance, some physicians and surgeons, rather than concede their helplessness, may resort to extreme measures, such as exploratory thoracotomy, laparotomy, or laminectomy. Or they may injudiciously attempt to alleviate the pain and avoid drug addiction by severing roots and spinal tracts, often with the result that the pain moves to an adjacent segment or to the other side of the body.


Neurology_Adams

Neurology_Adams. This type of patient benefits from being seen frequently by the same physician. All the medical facts should be reviewed and the clinical and laboratory examinations repeated if some time has elapsed since they were last done. Tumors in the hilum of the lung or mediastinum; in the retropharyngeal, retroperitoneal, and paravertebral spaces; or in the uterus, testicle, kidney, or prostate pose a special difficulty in diagnosis and are often undetected for many months. More than once, we have seen a patient for months before a kidney or pancreatic tumor became apparent. Neurofibroma causing pain in an unusual site, such as one side of the rectum or vagina, is another type of tumor that may defy diagnosis for a long time.


Neurology_Adams

Neurology_Adams. Truly neurogenic pain is almost invariably accompanied by alterations in cutaneous sensation and other neurologic signs, the finding of which facilitates diagnosis; however, the appearance of the neurologic signs may be delayed—for example, in brachial neuritis. Whether investigation for earlier mentioned abnormalities of the sodium and potassium channels in cases of idiopathic severe unexplained pain is advisable has not been established. The frequent attribution of such pains to an unspecified small fiber neuropathy may be valid but also requires further study.


Neurology_Adams

Neurology_Adams. Because of the complexity and difficulty in diagnosis and treatment of chronic pain, most medical centers have found it advisable to establish pain clinics. Here a staff of physiatrists, internists, anesthesiologists, neurologists, neurosurgeons, and psychiatrists can review each patient in terms of drug dependence, neurologic disease, and psychiatric problems. Success is achieved by treating each aspect of chronic pain, addressing the individual’s problems rather than treating the pain generically, with emphasis on increasing the patient’s tolerance of pain by means of biofeedback, meditation, and related techniques; by using special analgesic procedures (discussed later in the chapter); by establishing a regimen of pain medication that does not lead to a rebound exaggeration of pain between doses; and by controlling depressive illness. Rare and Unusual Disturbances of Pain Perception


Neurology_Adams

Neurology_Adams. Rare and Unusual Disturbances of Pain Perception Lesions of the parietooccipital regions of one cerebral hemisphere sometimes have peculiar effects on the patient’s capacity to feel and react to pain. Under the title of pain hemiagnosia, Hecaen and Ajuriaguerra described several cases of left-sided paralysis from a right parietal lesion, which, at the same time, rendered the patient hypersensitive to noxious stimuli. When pinched on the affected side, the patient, after a delay, became agitated, moaned, and seemed distressed but made no effort to fend off the painful stimulus with the other hand or to withdraw from it. In contrast, if the good side was pinched, the patient reacted normally and moved the normal hand at once to the site of the stimulus to remove it. The motor responses seemed no longer to be guided by sensory information from one side of the body.


Neurology_Adams

Neurology_Adams. There are also two varieties of rare individuals who from birth are totally indifferent to pain coupled with anhidrosis (“congenital insensitivity to pain”) or are incapable of feeling pain (“universal analgesia”). The former have been found by Indo and colleagues to have a mutation in the neural tyrosine kinase receptor, a nerve growth factor receptor; those in the second group suffer from either a congenital lack of pain neurons in dorsal root ganglia or from a mutation in the sodium channel discussed earlier. A similar loss of pain sensibility is encountered in the Riley-Day syndrome (congenital dysautonomia, see Chap. 25). Neuropathic pain syndromes predicated on sodium channel abnormalities have already been mentioned.


Neurology_Adams

Neurology_Adams. The phenomenon of asymbolia for pain is another rare and unusual condition wherein the patient, although capable of distinguishing the different types of pain stimuli from one another and from touch, is said to make none of the usual emotional, motor, or verbal responses to pain. The patient seems totally unaware of the painful or hurtful nature of stimuli delivered to any part of the body, whether on one side or the other. The current interpretation of asymbolia for pain is that it represents a particular type of agnosia (analgognosia) or apractagnosia (see Chap. 21), in which the person loses his ability to adapt his emotional, motor, and verbal actions to the consciousness of a nociceptive impression. Prefrontal lobe lesions from stroke, trauma, tumor, or in former times, frontal lobotomy, can produce a version of this syndrome.


Neurology_Adams

Neurology_Adams. Once the nature of the patient’s pain and underlying disease has been determined, therapy must include some type of pain control. Initially, of course, attention is directed to the underlying disease with the idea of eliminating the source of the pain by appropriate medical, surgical, or radiotherapeutic measures. When the primary disease is not treatable, the physician should, if time and the circumstances permit, attempt to use the milder measures for pain relief first—for example, nonnarcotic analgesics and antidepressants or antiepileptic drugs before resorting to narcotics, local nerve blocks or contemplating surgical approaches for pain relief. Not all situations allow this graduated approach, and large doses of narcotics may be required early in the course of some illnesses—for example, to treat the pain of visceral and bone cancer. The same measured strategy is appropriate in the treatment of neuropathic pain and of pain of unclear origin except that one generally stops short


Neurology_Adams

Neurology_Adams. to treat the pain of visceral and bone cancer. The same measured strategy is appropriate in the treatment of neuropathic pain and of pain of unclear origin except that one generally stops short of ablative procedures that irrevocably damage nerves or parts of the central nervous system.


Neurology_Adams

Neurology_Adams. The field of pain relief was altered by the introduction of analgesic procedures that block nerves, alter neural conduction, or administer conventional medications in new ways. In addition, a number of procedures such as intrathecal pumps and spinal cord stimulators and medications are effective for pain relief but are unique to specific situations. For example, trigeminal neuralgia may be relieved by microvascular decompression of a branch of the basilar artery or by controlled damage of the gasserian ganglion; painful dystonic disorders may be relieved by the intramuscular injection of botulinum toxin. The following discussion provides some guidance for the physician who is asked to undertake or participate in the treatment of chronic pain or of neuropathic pain.


Neurology_Adams

Neurology_Adams. Antidepressants and antiepileptic drugs, as discussed further on, may have a beneficial effect on pain even in the absence of overt depression. This is considered to be true particularly in cases of neuropathic pain (painful polyneuropathy and some types of radicular pain). Sometimes these nonnarcotic agents may, in themselves or in combination with these treatment modalities, be sufficient to control the patient’s pain and the use of narcotics can then be kept in reserve.


Neurology_Adams

Neurology_Adams. Should the foregoing measures prove to be ineffective, one may turn to narcotic agents. In chronic disease, methadone and related drugs are sometimes useful with which to begin because of their effectiveness by mouth and the relatively slow development of tolerance. Some pain specialists prefer the use of shorter-acting drugs such as oxycodone, hydrocodone, given more frequently through the day. Longer acting, orally administered drugs are used but may also be problematic because the doses may be more difficult to manage. The oral route should be used whenever possible, as it is more comfortable for the patient than the parenteral route. Also, the oral route is associated with fewer side effects except for nausea and vomiting. Nevertheless, should parenteral administration be necessary, one must be aware of the ratios of oral-to-parenteral dosages required to produce equivalent analgesia. The main medications used in the treatment of pain are summarized in Table 7-3.


Neurology_Adams

Neurology_Adams. A useful way in which to undertake the management of chronic pain that affects several parts of the body, as in the patient with metastases, is with narcotics taken together with aspirin, acetaminophen, or another analgesic drug. The analgesic effects of these types of drugs are additive, which is not the case when narcotics are combined with benzodiazepines.


Neurology_Adams

Neurology_Adams. If oral medication fails to control the pain, the parenteral administration of opioids may become necessary. One may begin with morphine, dihydromorphine, or levorphanol, given at intervals of 4 to 6 h because of their relatively long duration of action (particularly in comparison to meperidine). Alternatively, one may first resort to the use of transdermal patches of drugs such as fentanyl, which provide relief for 24 to 72 h and which we have found particularly useful in the treatment of pain from brachial or lumbosacral plexus invasion by tumor and of painful neuropathies such as those caused by diabetes and systemic amyloidosis. Long-acting morphine preparations are useful alternatives.


Neurology_Adams

Neurology_Adams. Should long-continued injections of opiates become necessary, the optimal dose for the relief of pain should be established and the drug then ideally given at regular intervals, rather than “as needed” in order to avoid breakthrough pain that requires higher cumulative doses of drugs. The administration of morphine (and other narcotics) in this way represents a laudable shift in attitude among physicians because for many years it was widely believed that the drug should be given in the smallest possible doses, spaced as far apart as possible, and repeated only when severe pain reasserted itself. It has become clear that this approach results in unnecessary discomfort and, in the end, the need to use larger doses. Most physicians now realize that the fear of creating narcotic dependence and the expected phenomenon of increasing tolerance must be balanced against the overriding need to relieve pain. The most pernicious aspect of addiction, that of compulsive drug-seeking behavior with


Neurology_Adams

Neurology_Adams. the expected phenomenon of increasing tolerance must be balanced against the overriding need to relieve pain. The most pernicious aspect of addiction, that of compulsive drug-seeking behavior with its attendant sociopathic behaviors, occurs only infrequently in this setting and usually in patients with a previous history of addiction or alcoholism, with depression as the primary problem, or with certain traits that have been loosely referred to as “addiction proneness,” which may have genetic components. Even in patients with severe acute or postoperative pain, the best results are obtained by allowing the patient to determine the dose and frequency of intravenous medication, a method known as patient-controlled analgesia (PCA). Again, the danger of producing addiction is minimal.


Neurology_Adams

Neurology_Adams. Guidelines for the use of orally and parenterally administered opioids for general and cancer-related pain are contained in numerous publications, most of which converge on similarly structured plans. The document issued by the U.S. Department of Health and Human Services in 1994 had great influence and still can be used as a basic resource for cancer pain treatment (the primary source and a special report referring to it by Jacox and colleagues are given in the references). Supplemental Medications for the Treatment of Pain


Neurology_Adams

Neurology_Adams. Supplemental Medications for the Treatment of Pain Tricyclic antidepressants, especially the methylated forms (imipramine, amitriptyline, and doxepin), block serotonin reuptake and thus enhance the action of this neurotransmitter at synapses and putatively facilitate the action of the intrinsic opiate analgesic system. As a general rule, relief is afforded with tricyclic antidepressants in the equivalent dose range of 75 to 125 mg daily of amitriptyline, but little benefit accrues with higher amounts. The specific serotonin reuptake inhibitors (SSRI) antidepressants seem not to be as effective for the treatment of chronic neuropathic pain (see review by McQuay and colleagues) but these agents have not yet been extensively investigated in this clinical condition.


Neurology_Adams

Neurology_Adams. Certain antiepileptic drugs (AEDs) have a beneficial effect on many central and peripheral neuropathic pain syndromes but are generally less effective for causalgic pain caused by partial injury of a peripheral nerve. The mode of action of phenytoin, carbamazepine, gabapentin, levetiracetam, and other AEDs in suppressing the lancinating pains of tic douloureux and certain polyneuropathies, as well as pain after spinal cord injury and myelitis, is not fully understood, but they are widely used. Their action has been attributed to the blocking of sodium channels on axons, thereby reducing the evoked and spontaneous activity in nerve fibers. The full explanation is certainly more complex and related to separate central and peripheral sites, as summarized by Jensen. Often, large doses must be utilized—for example, more than 2,400 mg per day for gabapentin for full effect—but the soporific and ataxic effects of these medications may be poorly tolerated.


Neurology_Adams

Neurology_Adams. Most often a combination of medications is used for the treatment of intractable chronic pain. A common combination is the addition of gabapentin to an opioid such as morphine; perhaps not surprisingly, this was superior to either drug alone in a crossover trial in patients with postherpetic neuralgia and diabetic neuropathy conducted by Gilron and colleagues. Table 7-3 summarizes the main analgesics (nonnarcotic and narcotic), antiepileptics, and antidepressant drugs in the management of chronic pain. Treatment of Neuropathic Pain


Neurology_Adams

Neurology_Adams. The treatment of pain induced by nerve root or intrinsic peripheral nerve disease is a challenge for the neurologist and includes several techniques that are generally administered by an anesthesiologist. One usually resorts first to one of the antiepileptic drugs discussed earlier and listed in Table 7-3. The next simplest treatments are topical; if the pain is regional and has a predominantly burning quality, capsaicin cream can be applied locally, care being taken to avoid contact with the eyes and mouth. The irritative effect of this chemical, which releases substance P, seems in some cases to mute the pain. There has also been limited success with several “eutectic” mixtures of local anesthetic (EMLA) creams or the simpler lidocaine gel with ketorolac, gabapentin, and other medications; these are applied directly to the affected area, usually the feet, in the morning and evening. Concoctions such as topical ketamine mixed in soy lecithin to produce a gel with drug concentration


Neurology_Adams

Neurology_Adams. these are applied directly to the affected area, usually the feet, in the morning and evening. Concoctions such as topical ketamine mixed in soy lecithin to produce a gel with drug concentration of 5 mg/mL, have been reportedly useful in treating post herpetic neuralgia according to Quan and associates in a small randomized trial and similarly, aspirin compounded with cold cream or, if available, chloroform. These preparations may provide some relief in postherpetic neuralgia and painful peripheral neuropathies.


Neurology_Adams

Neurology_Adams. Several types of spinal injections, including epidural, root, and facet blocks, have long been used for the treatment of spinal pain. Injections of epidural corticosteroids or mixtures of analgesics and steroids have been helpful in selected cases of lumbar or thoracic nerve root pain, and occasionally in painful peripheral neuropathy, but precise criteria for the use of this measure are not established. Several randomized trials have failed to support a long term beneficial effect of these treatments but a number of our patients have been helped, if only for several days or weeks (see Chap. 10 for a more complete discussion of these approaches). Nerve root blocks with lidocaine or with longer-acting local anesthetics are sometimes helpful in establishing the precise source of radicular pain. Their main therapeutic use in our experience has been for thoracic radiculitis from shingles, chest wall pain after thoracotomy, and diabetic radiculopathy. Similar local injections are used in


Neurology_Adams

Neurology_Adams. pain. Their main therapeutic use in our experience has been for thoracic radiculitis from shingles, chest wall pain after thoracotomy, and diabetic radiculopathy. Similar local injections are used in the treatment of occipital neuralgia. Injection of analgesic compounds into and around facet joints and the extension of this procedure, radiofrequency ablation of the small nerves that innervate the joint, are as controversial as epidural injections, with most studies failing to find a consistent benefit. Despite these drawbacks, we have found both of these approaches useful when pain can be traced specifically to a derangement of these spinal joints, as discussed in Chap. 10.


Neurology_Adams

Neurology_Adams. The intravenous infusion of lidocaine may have a brief beneficial effect on many types of pain, including neuropathic varieties, localized headaches, trigeminal neuralgia, and other facial pains; it is said to be useful in predicting the response to longer-acting agents such as mexiletine, its oral analogue, although this relationship has been erratic in our experience. Mexiletine is given in an initial dose of 150 mg per day and slowly increased to a maximum of 300 mg three times daily; it should be used very cautiously in patients with heart block and has fallen very much out of favor in many centers, partly due to cardiac conduction abnormalities and rare instances of torsade de pointe arrhythmia during and after administration.


Neurology_Adams

Neurology_Adams. Reducing sympathetic activity within somatic nerves by direct injection of the sympathetic ganglia in affected regions of the body (stellate ganglion for arm pain and lumbar ganglia for leg pain) has met with mixed success in neuropathic pain, including that of causalgia and reflex sympathetic dystrophy. A variant of this technique uses regional intravenous infusion of a sympathetic-blocking drug (bretylium, guanethidine, reserpine) into a limb that is isolated from the systemic circulation by the use of a tourniquet. This is known as a “Bier block,” after the developer of regional anesthesia for single-limb surgery. These techniques, as well as the administration of clonidine by several routes and the intravenous infusion of the adrenergic blocker phentolamine, is predicated on the concept of “sympathetically sustained pain,” meaning pain that is mediated by the interaction of sympathetic and pain nerve fibers or by the sprouting of adrenergic axons in partially damaged nerves. These


Neurology_Adams

Neurology_Adams. of “sympathetically sustained pain,” meaning pain that is mediated by the interaction of sympathetic and pain nerve fibers or by the sprouting of adrenergic axons in partially damaged nerves. These forms of treatment have been under study for many decades and have given variable results but the most consistent responses to regional sympathetic blockade are obtained in cases of causalgia resulting from partial injury of a single nerve (CRPS I).


Neurology_Adams

Neurology_Adams. A number of other treatments have proven successful in some patients with reflex sympathetic dystrophy and other neuropathic pains but the clinician should be cautious about their chances of success over the long run. One of these has been bisphosphonates (pamidronate, alendronate), which have been beneficial in painful disorders of bone, such as Paget disease and metastatic bone lesions. It is theorized that this class of drug reverses the bone loss consequent to reflex sympathetic dystrophy but how this relates to pain control is unclear (Schott, 1997). Electrical stimulation of the posterior columns of the spinal cord by an implanted device, as discussed below, has become popular. Another treatment of last resort is the intravenous or epidural infusion of drugs such as ketamine; sometimes this has a lasting effect on causalgic pain.


Neurology_Adams

Neurology_Adams. The approaches enumerated here are usually undertaken in sequence; a combination of drugs—such as antiepileptics, narcotics, and clonidine—in addition to anesthetic techniques—is usually required. The ongoing attention and support of the neurologist is often a cornerstone of a successful treatment plan. Further references can be found in the thorough review by Katz. Ablative Surgery in the Control of Pain Only when a variety of analgesic medications (including opioids) and other practical measures, such as regional analgesia or anesthesia, have completely failed, should one turn to neurosurgical procedures. Also, one should be very cautious in suggesting a procedure of last resort for pain that has no established cause as, for example, limb pain that has been incorrectly identified as causalgic because of a burning component but where there has been no nerve injury.


Neurology_Adams

Neurology_Adams. The least-destructive procedure consists of surgical exploration for a neuroma if a prior injury or operation may have partially sectioned a peripheral nerve. Magnetic resonance imaging of the region should be performed first and will demonstrate most such lesions, but we are uncertain if all small neuromas are visualized, and it is this ambiguity that justifies exploration. Another nondestructive procedure is implantation of a spinal electrical stimulator, usually adjacent to the posterior columns.


Neurology_Adams

Neurology_Adams. This procedure, in which there is now a resurgence of interest, has afforded only incomplete relief in our patients and may be difficult to maintain in place. However Kemler (2004) and colleagues found a sustained reduction in pain intensity and an improved quality of life in patients with intractable reflex sympathetic dystrophy, even after 2 years in a randomized trial. Others have found it less durable. It is clear that careful selection of patients, including a test trial of an externalized device, is partial assurance of a good outcome. The ill-advised use of nerve section and dorsal rhizotomy as definitive measures for the relief of regional pain was discussed above under “Treatment of Pain.” However, with regard to ablative procedures, the risks are great and the results can be unpredictable. Neurosurgeons, therefore, have largely abandoned the operations enumerated below. They are, however, sometimes performed for intractable pain produced by cancer.


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Neurology_Adams. Spinothalamic tractotomy, in which the anterior half of the spinal cord on one side is sectioned at an upper thoracic level, effectively relieves pain in the opposite leg and lower trunk but is now infrequently performed. This may be done as an open operation or as a transcutaneous procedure in which a radiofrequency lesion is produced by an electrode. The analgesia and thermoanesthesia may last a year or longer, after which the level of analgesia tends to descend and the pain tends to return. Bilateral tractotomy is also feasible but with greater risk of loss of sphincteric control and, at higher levels, of respiratory paralysis. Motor power is nearly always spared because of the position of the corticospinal tract in the posterior part of the lateral funiculus.


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Neurology_Adams. Pain in the arm, shoulder, and neck is more difficult to relieve surgically. High cervical transcutaneous cordotomy had been used successfully, with achievement of analgesia up to the chin. Commissural myelotomy by longitudinal incision of the anterior or posterior commissure of the spinal cord over many segments has also been performed, with variable success. Dorsal root entry zone (DREZ) lesions may temporarily relieve pain in the distribution of one or two nerve roots. Lateral medullary tractotomy is another possibility but must be carried almost to the mid-line to relieve cervical pain.


Neurology_Adams

Neurology_Adams. Stereotactic surgery on the thalamus for one-sided chronic pain is still used in a few centers and the results have been instructive. Lesions placed in the ventroposterior nucleus are said to diminish pain and thermal sensation over the contralateral side of the body while leaving the patient with all the misery or affective experience of pain; lesions in the intralaminar or parafascicular- centromedian nuclei relieve the painful state without altering sensation (Mark). As mentioned, because these procedures have not yielded predictable benefits to the patient, they are now seldom used. The same unpredictability pertains to cortical ablations. Patients in whom a severe depression of mood is associated with a chronic pain syndrome have been subjected to bilateral stereotactic cingulotomy or the equivalent—subcaudate tractotomy. A degree of success had been claimed for these operations but the results are difficult to evaluate. Orbito-frontal leukotomy has been discarded because of the


Neurology_Adams

Neurology_Adams. the equivalent—subcaudate tractotomy. A degree of success had been claimed for these operations but the results are difficult to evaluate. Orbito-frontal leukotomy has been discarded because of the personality change that it produces. Although not an established indication, some work has been done on stimulation of the dorsal cingulate for chronic pain and on other forms of electrical and magnetic stimulation of various brain structures.


Neurology_Adams

Neurology_Adams. Nonmedical Methods for the Treatment of Pain Included under this heading are certain techniques such as biofeedback, meditation, imagery, acupuncture, spinal manipulation, as well as transcutaneous electrical stimulation. Among the most intriguing treatments for patients with complex regional pain syndrome or phantom limb pain, has been mirror therapy, in which the patient is instructed to perform movements in the painful arm while observing the unaffected arm in a mirror (Cacchio et al).


Neurology_Adams

Neurology_Adams. Each of the aforementioned methods may be of value in the context of a comprehensive pain management program, usually conducted in a pain clinic as a means of providing relief from pain and suffering, reducing anxiety, and diverting the patient’s attention, even if only temporarily, from the painful body part. Attempts to quantify the benefits of these techniques—judged usually by a reduction of drug dosage—have given mixed or negative results. Nevertheless, it is unwise for physicians to dismiss these methods, as well-motivated and apparently psychologically stable persons have reported improvement with one or another of these methods and in the final analysis, this is what really matters. Conventional psychotherapy in combination with the use of medication and, at times, electroconvulsive therapy can be of benefit in the treatment of associated depressive symptoms, as discussed above (under “Pain in Association with Psychiatric Diseases”) but it should not otherwise be expected to


Neurology_Adams

Neurology_Adams. therapy can be of benefit in the treatment of associated depressive symptoms, as discussed above (under “Pain in Association with Psychiatric Diseases”) but it should not otherwise be expected to change the experience of pain.


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Neurology_Adams. Similarly, the role of placebo in all branches of medicine is being explored, nowhere more saliently than for pain. Kaptchuk and Miller have indicated in their review that the placebo effect rests upon the qualities of the therapeutic encounter but appears to work through conventional neurobiological mechanisms including endogenous opioids as found by Fields and Levine. Their review gives persuasive examples of placebo effects in migraine and other painful neurologic conditions. Whatever treatment is undertaken, medical, procedural or surgical, the objective should be to allow and encourage increased use and mobilization of the affected limb or part, as success at this is most closely associated with relief of pain and reduced suffering. Asbury AK, Fields HL: Pain due to peripheral nerve damage: an hypothesis. Neurology 34:1587, 1984. Benarroch E: Ion channels in nociceptors. Neurology 84:1153, 2015.


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Neurology_Adams. Asbury AK, Fields HL: Pain due to peripheral nerve damage: an hypothesis. Neurology 34:1587, 1984. Benarroch E: Ion channels in nociceptors. Neurology 84:1153, 2015. Bhatia KP, Bhatt MH, Marsden CD: The causalgia-dystonia syndrome. Brain 116:843, 1993. Cacchio A, DeBlasis E, Neconzione S, et al: Mirror therapy for chronic complex regional pain syndromes type I and stroke. N Engl J Med 361:634, 2009. DeBroucker TH, Cesaro P, Willer JC, LeBars D: Diffuse noxious inhibitory controls in man: involvement of the spino-reticular tract. Brain 113:1223, 1990. Dyck PJ, Lambert EH, O’Brien PC: Pain in peripheral neuropathy related to rate and kind of fiber degeneration. Neurology 26:466, 1976. Fertleman CR, Ferrie CD, Aicardi J, et al: Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology 69:586, 2007. Fields HL: Depression and pain: a neurobiological model. Neuropsychiatry Neuropsychol Behav Neurol 4:83, 1991.


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Neurology_Adams. Fields HL: Depression and pain: a neurobiological model. Neuropsychiatry Neuropsychol Behav Neurol 4:83, 1991. Fields HL (ed): Pain Syndromes in Neurology. Oxford, Butterworth, 1990. Fields HL: Pain. New York, McGraw-Hill, 1987. Fields HL, Levine JD: Placebo analgesia—a role for endorphins? Trends Neurosci 7:271, 1984. Fischer TZ, Waxman SG: Familial pain syndromes from mutations of the NaV1.7 sodium channel. Ann N Y Acad Sci 1184:196, 2010. Fruhstorfer H, Lindblom U: Sensibility abnormalities in neuralgic patients studied by thermal and tactile pulse stimulation. In: von Euler C (ed): Somatosensory Mechanisms. Wenner-Grenn International Symposium Series. New York, Plenum Press, 1984, pp 353–361. Gilron I, Bailey JM, Tu D: Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 352:1324, 2005. Goldscheider A: Ueber den Schmerz in Physiologischer und Klinischer Hinsicht. Berlin, Hirschwald, 1884.


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Neurology_Adams. Goldscheider A: Ueber den Schmerz in Physiologischer und Klinischer Hinsicht. Berlin, Hirschwald, 1884. Head H, Rivers WHR, Sherren J: The afferent nervous system from a new aspect. Brain 28:99, 1905. Hecaen H, Ajuriaguerra J: Asymbolie è la douleur, ètude anatomoclinique. Rev Neurol 83:300, 1950. Indo Y, Tsurata M, Hayashida Y, et al: Mutations in the TRK/NGF receptor gene in patients with congenital insensitivity to pain and anhidrosis. Nat Genet 13:458, 1996. Inman VT, Saunders JB: Referred pain from skeletal structures. J Nerv Ment Dis 99:660, 1944. Jacox A, Carr DB, Payne RM: New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med 330:651, 1994. Jensen TS: Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain 6(Suppl A):61, 2002. Kaptchuk TJ, Miller FG: Placebo effects in medicine. N Engl J Med 373:8, 2015. Katz N: Role of invasive procedures in chronic pain management. Semin Neurol 14:225, 1994.


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Neurology_Adams. Kaptchuk TJ, Miller FG: Placebo effects in medicine. N Engl J Med 373:8, 2015. Katz N: Role of invasive procedures in chronic pain management. Semin Neurol 14:225, 1994. Kellgren JH: On the distribution of pain arising from deep somatic structures with charts of segmental pain areas. Clin Sci 4:35, 1939. Kemler MA, Barandse GAM, van Kleef M, et al: Spinal cord stimulation in patients with reflex sympathetic dystrophy. N Engl J Med 343:618, 2000. Kemler MA, Henrica CW, Barendse G, et al: The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years’ follow-up of the randomized controlled trial. Ann Neurol 55:13, 2004. Klein CJ, Lennon V, Aston PA, et al: Chronic pain as a manifestation of potassium channel-complex autoimmunity. Neurology 79:1136, 2012. Lele PP, Weddell G: The relationship between neurohistology and corneal sensibility. Brain 79:119, 1956.


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Neurology_Adams. Lele PP, Weddell G: The relationship between neurohistology and corneal sensibility. Brain 79:119, 1956. Levine JD, Gordon NC, Fields HL: The mechanism of placebo analgesia. Lancet 2:654, 1978. Mark VH: Stereotactic surgery for the relief of pain. In: White JC, Sweet WH (eds): Pain and the Neurosurgeon. Springfield, IL, Charles C Thomas, 1969, pp 843–887. McQuay HJ, Tramer M, Nye BA, et al: A systematic review of antidepressants in neuropathic pain. Pain 68:217, 1996. Melzack R, Casey KL: Localized temperature changes evoked in the brain by somatic stimulation. Exp Neurol 17:276, 1967. Melzack R, Wall PD: Pain mechanism: a new theory. Science 150:971, 1965. Nathan PW: The gate-control theory of pain: a critical review. Brain 99:123, 1976. Price DD: Psychological and neural mechanisms of the affective dimension of pain. Science 288:1769, 2000. Quan D, Wellish M, Gilden DH: Topical ketamine treatment of post-herpetic neuralgia. Neurology 60:1391, 2003.


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Neurology_Adams. Quan D, Wellish M, Gilden DH: Topical ketamine treatment of post-herpetic neuralgia. Neurology 60:1391, 2003. Rexed B: A cytotectonic atlas of the spinal cord in the cat. J Comp Neurol 100:297, 1954. Reynolds DV: Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 164:444, 1969. Rothstein RD, Stecker M, Reivich M, et al: Use of positron emission tomography and evoked potentials in the detection of cortical afferents from the gastrointestinal tract. Am J Gastroenterol 91:2372, 1996. Scadding JW: Neuropathic pain. In: Asbury AK, McKhann GM, McDonald WI (eds): Diseases of the Nervous System: Clinical Neurobiology, 2nd ed. Philadelphia, Saunders, 1992, pp 858–872. Schmahmann JD, Leifer D: Parietal pseudothalamic pain syndrome: Clinical features and anatomic correlates. Arch Neurol 49:1032, 1992. Schott GD: Bisphosphonates for pain relief in reflex sympathetic dystrophy. Lancet 350:1117, 1997.


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Neurology_Adams. Schott GD: Bisphosphonates for pain relief in reflex sympathetic dystrophy. Lancet 350:1117, 1997. Schott GD: From thalamic syndrome to central poststroke pain. J Neurol Neurosurg Psychiatry 61:560, 1996. Schott GD: Mechanisms of causalgia and related clinical conditions. Brain 109:717, 1986. Schott GD: Reflex sympathetic dystrophy. J Neurol Neurosurg Psychiatry 71:291, 2001. Schwartzman RJ, McLellan TL: Reflex sympathetic dystrophy: a review. Arch Neurol 44:555, 1987. Silverman DH, Munakata JA, Ennes H, et al: Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 112:64, 1997. Snyder SH: Opiate receptors in the brain. N Engl J Med 296:266, 1977. Taub A, Campbell JN: Percutaneous local electrical analgesia: peripheral mechanisms. In: Advances in Neurology. Vol 4: Pain. New York, Raven Press, 1974, pp 727–732. Trotter W, Davies HM: Experimental studies in the innervation of the skin. J Physiol 38:134, 1909.


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Neurology_Adams. Trotter W, Davies HM: Experimental studies in the innervation of the skin. J Physiol 38:134, 1909. U.S. Department of Health and Human Services: Management of Cancer Pain: Clinical Practice Guideline Number 9. AHCPR Publications No. 94-0592 and 94-0593, Rockville, Public Health Service, Agency for Health Care Policy and Research, March 1994. Von Euler US, Gaddum JH: An unidentified depressor substance in certain tissue extracts. J Physiol 70:74, 1931. Von Frey M: Untersuchungen Über die Sinnesfunctionen der menschlichen Haut: I. Druckempfindung und Schmerz. Königl Sächs Ges Wiss Math Phys Kl 23:175, 1896. Wager, TD, Atlas LY, Lindquist MA, et al: An fMRI-based neurologic signature of physical pain. N Engl J Med 368:1388, 2013. Wall PD, Melzack R (eds): Textbook of Pain, 4th ed. New York, Churchill Livingstone, 1999. Walshe FMR: The anatomy and physiology of cutaneous sensibility: a critical review. Brain 65:48, 1942.


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Neurology_Adams. Wall PD, Melzack R (eds): Textbook of Pain, 4th ed. New York, Churchill Livingstone, 1999. Walshe FMR: The anatomy and physiology of cutaneous sensibility: a critical review. Brain 65:48, 1942. Weddell G: The anatomy of cutaneous sensibility. Br Med Bull 3:167, 1945. Wells KB, Stewart A, Hays RD, et al: The functioning and well-being of depressed patients. JAMA 262:914, 1989. White D, Helme RD: Release of substance P from peripheral nerve terminals following electrical stimulation of sciatic nerve. Brain Res 336:27, 1985. Woolf CJ: Pain: Moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 140:441, 2004. Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353:1959, 1999.


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Neurology_Adams. Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353:1959, 1999. Figure 7-1. A. Spinal cord in transverse section illustrating the course of the afferent fibers and the major ascending pathways. Fast-conducting pain fibers are not confined to the spinothalamic tract but are scattered diffusely in the anterolateral funiculus (see also Fig. 7-3). (Adapted from Martin JH: Neuroanatomy: Text and Atlas. New York, McGraw-Hill, 2003, with permission.) B. Transverse section through a cervical segment of the spinal cord illustrating the subdivision of the gray matter into laminae according to Rexed and the entry and termination of the main sensory fibers. (Adapted from Fields HL: Pain. New York, McGraw-Hill, 1987, with permission.)


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Neurology_Adams. Figure 7-2. The spinothalamic and trigeminothalamic tracts (pain, thermal sense) are shown. In the bottom section, the fibers that form the spinothalamic tract cross over two or three segment rostral to their entry into the cord, not at the same level as depicted. Offshoots from the ascending anterolateral fasciculus (spinothalamic tract) to nuclei in the medulla, pons, and mesencephalon and nuclear terminations of the tract are indicated. The cortical representation of sensation is shown grossly; it is shown more explicitly in Fig. 8-5 and discussed in Chap. 8. The lemniscal (posterior column) system is shown in Fig. 8-4.


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Neurology_Adams. Figure 7-3. Spinal cord showing the segmental and laminated arrangement of nerve fibers within major tracts. On the left side are indicated the “sensory modalities” that appear to be mediated by the two main ascending pathways. C, cervical; T, thoracic; L, lumbar; S, sacral. (Adapted by permission from Brodal A: Neurological Anatomy, 3rd ed. New York, Oxford University Press, 1981.) Figure 7-4. Mechanism of action of enkephalin (endorphin) and morphine in the transmission of pain impulses from the periphery to the CNS. Spinal interneurons containing enkephalin synapse with the terminals of pain fibers and inhibit the release of the presumptive transmitter, substance P. As a result, the receptor neuron in the dorsal horn receives less excitatory (pain) impulses and transmits fewer pain impulses to the brain. Morphine binds to unoccupied enkephalin receptors, mimicking the pain-suppressing effects of the endogenous opiate enkephalin.


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Neurology_Adams. Figure 7-5. Sclerotome maps taken from Inman and Saunders with permission. The projections of pain from osteal and periosteal structures such as ligaments were established by the injection of hypertonic saline or formic acid into the upper extremity (A) and lower extremity (B) and can also be found in the articles of Kellgren. They may be compared to the dermatomal maps shown in Figs. 9-1 through 9-3. Disorders of Non-Painful Somatic Sensation


Neurology_Adams

Neurology_Adams. The preceding chapter dealt with pain and its pathways and mechanisms. There are, of course, several other somatosensory experiences that also utilize specialized end organs, pathways, and neurophysiologic mechanisms; these include touch, vibration and joint position senses, appreciation of deep pressure, as well as integrated sensory experiences that depend on cortical functions and are the subject of the current chapter. The separation between these two broad somatosensory systems is logical in so far as each depends on distinctive tracts in the peripheral nerves, spinal cord, and brain. In clinical practice, however, they are tested in parallel and give complementary information regarding the localization and nature of a lesion. Because the peripheral nervous system is organized in a segmental pattern, the superficial representation of all sensation, nociceptive and non-nociceptive, follows the dermatomal and peripheral nerve map shown in Fig. 8-1.


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Neurology_Adams. The sphere of tactile sensory experiences is every bit as rich as that originating in vision and audition. The receptors that translate mechanical forces on the skin are varied and incredibly well suited to allow the brain to distinguish between subtle experiences, from the texture of water to the coarseness of sand between the fingers. Furthermore, sensory and motor functions are interdependent, as was dramatically illustrated by the early animal experiments of Claude Bernard and Charles Sherrington, in which practically all effective movement of a limb was abolished by eliminating only its sensory innervation (sectioning of posterior roots). Interruption of other sensory pathways and destruction of the parietal cortex also has profound effects on motility. To a large extent, human motor activity depends on a constant influx of sensory impulses (most of them not consciously perceived). Sensory-motor integration is therefore necessary for normal nervous system function but disease may


Neurology_Adams

Neurology_Adams. activity depends on a constant influx of sensory impulses (most of them not consciously perceived). Sensory-motor integration is therefore necessary for normal nervous system function but disease may affect motor or sensory functions independently. There also may be loss or impairment of sensory function, and this can represent the principal manifestation of neurologic disease.


Neurology_Adams

Neurology_Adams. All sensation depends on impulses that are excited by stimulation of receptors and conveyed to the central nervous system by afferent (sensory) fibers. Sensory receptors are of two general types: those in the skin, mediating superficial sensation (exteroceptors), and those in the deeper somatic structures (proprioceptors). Skin receptors are particularly numerous and transduce four types of sensory experience: warmth, cold, touch, and pain. Proprioceptors provide information on the position of the body or parts of the body; of the force, direction, and range of movement of the joints (kinesthetic sense); and a sense of pressure, both painful and painless. Histologically, a wide variety of sensory receptors have been described, from simple, free terminals to highly branched and encapsulated structures, the latter bearing the names of the anatomists who first described them (see below). In some texts these nerve endings are called “dendrites” because they are the distal processes of the


Neurology_Adams

Neurology_Adams. structures, the latter bearing the names of the anatomists who first described them (see below). In some texts these nerve endings are called “dendrites” because they are the distal processes of the sensory ganglion cell and the direction of flow of physiologic activity and of sensory information from these structures in the periphery is toward the cell body.


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Neurology_Adams. Mechanisms of Cutaneous Sensation As indicated in the preceding chapter, it had been thought that each of the primary modalities of cutaneous sensation is subserved by a morphologically distinct end organ, each with its separate peripheral nerve fibers. These can be broadly categorized as cutaneous and subcutaneous mechanoreceptors, muscle and joint mechanoreceptors, thermal receptors, and pain receptors (nociceptors). According to this formulation, postulated by von Frey and still largely correct but modified as noted further on, there is a degree of specificity for each receptor and nerve fiber type, each type of end organ responding preferentially to a modality of sensory stimulus. There are several cutaneous mechanoreceptors:


Neurology_Adams

Neurology_Adams. Meissner corpuscles (named after Georg Meissner), touch; Merkel discs (named after Friedrich Sigmund Merkel), pressure; Ruffini plumes (named after Angelo Ruffini), skin stretch; and Pacini (pacinian) corpuscles (named after Filippo Pacini), vibration, and several others that are more specialized. Likewise, several receptors subserve muscle force, length, and joint angle: the intrafusal muscle spindle, stretch and speed of contraction; Golgi tendon organ, muscle length; joint capsule receptors; joint angle; stretch sensitive-free endings, which is sensitive to force. There are also, as mentioned in the previous chapter, specialized nerve endings for temperature (cool and warm), for extremes of temperature (cold and hot) such as Krause end bulbs (named after Wilhelm Krause and also called bulboid receptors) for cold; and for pain, nerve endings that are not associated with a transducer (“free nerve endings”). The last of these are also termed “naked” because they are surrounded by


Neurology_Adams

Neurology_Adams. bulboid receptors) for cold; and for pain, nerve endings that are not associated with a transducer (“free nerve endings”). The last of these are also termed “naked” because they are surrounded by Schwann cells but are not myelinated (Table 8-1 and Fig. 8-2).


Neurology_Adams

Neurology_Adams. The specificity theory, expressed in the preceding paragraph, has been modified in respect to some somatosensory modalities. For example, Merkel discs and Meissner corpuscles and free nerve endings can all be activated by moving or stationary tactile stimuli. The concept of specificity has held up best in relation to peripheral mechanisms for pain, insofar as certain primary afferent fibers, namely the C and A-δ fibers and their free nerve endings, respond maximally to noxious stimuli. Even these freely branching receptor endings and their pain fibers convey considerable non-noxious information; that is, their specificity as pain fibers is not absolute (Chap. 7). Lele and Weddell found that with appropriate stimulation of the cornea, each of the four primary modalities of somatic sensibility (touch, warmth, cold, and pain) could be recognized, even though the cornea contains only free nerve endings. In the outer ear, which is also sensitive to these four modalities, only two types of


Neurology_Adams

Neurology_Adams. (touch, warmth, cold, and pain) could be recognized, even though the cornea contains only free nerve endings. In the outer ear, which is also sensitive to these four modalities, only two types of receptors—freely ending and perifollicular—are present. The lack of organized receptors in the cornea and ear makes it evident that these types of receptors are not essential for the recognition of cold and warmth as von Frey and other anatomists had postulated.


Neurology_Adams

Neurology_Adams. Instructive refinements of the specificity theory have emerged, based on observations by Kibler and Nathan, who studied the responses of warm and cold spots to different stimuli. Warm and cold spots are those small areas of skin that respond most consistently to thermal stimuli with a sensation of warmth or cold. They found that a cold stimulus applied to a warm spot gave rise to a sensation of cold and that a noxious stimulus applied to a warm or cold spot gave rise only to a painful sensation; they also noted that mechanical stimulation of these spots gave rise to a sensation of touch or pressure. These experiments indicate that cutaneous receptors, some not distinguishable from each other on morphologic grounds, are probably endowed with only relative degrees of specificity, in the sense that each responds preferentially (i.e., has a lower threshold) to one particular form of stimulation.


Neurology_Adams

Neurology_Adams. Physiologic studies have shown that rather than the type of receptor, the quality of sensation depends on the type of nerve fiber that is activated. Microstimulation of single sensory fibers in a peripheral nerve arouses different sensations, depending on which fibers are stimulated. The intensity of sensation, on the other hand, is governed by the frequency of stimulation and the number of sensory units that are stimulated. Stated somewhat differently, the magnitude or intensity of sensation is encoded by afferent impulse frequency (temporal summation). In addition, as the intensity of stimulation increases, more sensory units are activated (spatial summation).


Neurology_Adams

Neurology_Adams. Localization of a stimulus was formerly thought to depend on the simultaneous activation of overlapping sensory units. Tower defined a peripheral sensory unit as a dorsal root ganglion cell, its central and distal processes, and all the sensory endings in the territory supplied by those distal processes (the receptive field of the sensory cell). In the very sensitive pulp of the finger, where the error of localization is less than 1 mm, there are 240 overlapping, low-threshold mechanoreceptors per square centimeter. Specialized physiologic techniques have demonstrated that activation of even a single sensory unit is sufficient to localize the point stimulated and that the body map in the parietal lobe is capable, by its modular columnar organization, of encoding such refined topographic information. Also, each point in the skin that is stimulated may involve more than one type of receptor. To gain access to its receptor, a stimulus must pass through the skin and possess sufficient


Neurology_Adams

Neurology_Adams. information. Also, each point in the skin that is stimulated may involve more than one type of receptor. To gain access to its receptor, a stimulus must pass through the skin and possess sufficient energy to transduce, that is, depolarize, the nerve ending.


Neurology_Adams

Neurology_Adams. Another feature of the sensory endings is their variable adaptation to continued tactile forces. The impulse that is generated by a sensory ending is a graded one, not an all-or-none phenomenon like an action potential in nerve. This poorly understood peripheral generator determines the frequency of impulses in the nerve and to what degree the nerve response is sustained or fatigues. While anatomists have separated sensory receptors by morphology and physiologists classify them by the associated nerve fiber type as discussed below, there has been a trend to further separate receptors into low, or high-threshold type and to classify them by the rapidity of adaptation. Low-threshold receptors respond to weak and innocuous forces, and high threshold nerve endings are mainly nociceptive. The low-threshold ones show different patterns of adaptation depending on whether there is sustained firing during deformation (slowly adapting, mainly Merkel discs and Ruffini endings) or respond


Neurology_Adams

Neurology_Adams. The low-threshold ones show different patterns of adaptation depending on whether there is sustained firing during deformation (slowly adapting, mainly Merkel discs and Ruffini endings) or respond maximally to objects moving across the skin (rapidly adapting and firing at the onset and offset of stimuli, mainly Meissner and pacinian corpuscles). The high-threshold receptors can be separated by neuropeptide and other expression markers (see Abraira and Ginty for detailed discussion of these matters).


Neurology_Adams

Neurology_Adams. As just noted, each sensory end organ is most fully characterized by morphology and sensitivity to a particular stimulus, its physiologic characteristics of threshold and adaptation, and singularly, by the nerve fiber type to which it is connected. Fibers that mediate superficial sensation are located in cutaneous sensory or mixed sensorimotor nerves. In cutaneous nerves, unmyelinated pain and autonomic fibers exceed myelinated fibers by a ratio of 3 or 4:1. The myelinated fibers are of two types: small, lightly myelinated, A-d fibers for pain and cold, as discussed in Chap. 7 (see Table 7-1), and larger, faster-conducting A-α fibers for touch and pressure. Nonmyelinated autonomic fibers are efferent (postganglionic) and innervate piloerector muscles, sweat glands, and blood vessels. The differing conduction velocities of these fibers are discussed in Chap. 2.


Neurology_Adams

Neurology_Adams. Each cutaneous afferent fiber connects to several receptors of the same type (touch, pain, or temperature), which are irregularly distributed in the skin and account for what had been termed “sensory spots” as alluded to above and in the preceding chapter. Proprioceptive fibers subserve pressure sense and, with endings in articular structures, the sense of position and movement; they enable one to discriminate the form, size, texture, and weight of objects. However, sensations of tickle, itch, and wetness are believed to arise from combinations of several types of receptors. Itch, for example, is a distinctive sensation that can be separated on clinical and neurophysiologic grounds from touch and from pain. It is transmitted by specific C fibers, not by touch mechanisms; regions of analgesia no longer can be stimulated to itch but areas of anesthesia retain this sensation. The pathophysiology of itching has been discussed by Greaves and Wall and is reviewed further by Yosipovitch and


Neurology_Adams

Neurology_Adams. no longer can be stimulated to itch but areas of anesthesia retain this sensation. The pathophysiology of itching has been discussed by Greaves and Wall and is reviewed further by Yosipovitch and colleagues.


Neurology_Adams

Neurology_Adams. The sensory nerves are incorporated into plexi (lumbosacral, brachial plexus) and then divide into the dorsal roots. All the sensory neurons have their cell bodies in the dorsal root ganglia. The peripheral extensions of these cells are the sensory nerves; the central projections of these same cells form the posterior (dorsal) roots and enter the spinal cord. Each dorsal root contains all the fibers from skin, muscles, connective tissue, ligaments, tendons, joints, bones, and viscera that lie within the distribution of a single body segment (somite). This segmental innervation has been amply demonstrated in humans and animals by observing the effects of lesions that involve one or two spinal nerves, such as (1) herpes zoster, which also causes visible vesicles in the corresponding area of skin; (2) the effects of a prolapsed intervertebral disc, which causes hypalgesia in a single root zone; and (3) surgical section of several roots on each side of an intact root. Maps of the


Neurology_Adams

Neurology_Adams. area of skin; (2) the effects of a prolapsed intervertebral disc, which causes hypalgesia in a single root zone; and (3) surgical section of several roots on each side of an intact root. Maps of the dermatomes derived from these several types of data are shown in Figs. 8-1, 8-3 and 8-4. It should be noted that there is considerable overlap between adjacent dermatomal segments, more so for touch than for pain. By contrast, there is less overlap between adjacent peripheral nerves and almost none between the divisions of the trigeminal nerve. Also, the maps differ somewhat according to the methods used in constructing them. In contrast to most dermatomal charts, those of Keegan and Garrett (based on the injection of local anesthetic into single dorsal root ganglia) show bands of hypalgesia to be continuous longitudinally from the periphery to the spine (see Fig. 8-4). The distribution of pain fibers from deep structures, although not exactly corresponding to that of pain fibers from the


Neurology_Adams

Neurology_Adams. be continuous longitudinally from the periphery to the spine (see Fig. 8-4). The distribution of pain fibers from deep structures, although not exactly corresponding to that of pain fibers from the skin, also follows a segmental pattern. In Chap. 7 it was commented that the areas of projection of referred pain from the visceral organs and musculoskeletal structures roughly correspond to the overlying dermatomes but they have distinctive patterns, termed sclerotomes (see Fig. 7-5).


Neurology_Adams

Neurology_Adams. Posterior Root Entry Zone, Dorsal Horns,


Neurology_Adams

Neurology_Adams. In the dorsal roots, the sensory fibers are first rearranged according to function. Large and heavily myelinated fibers enter the cord just medial to the dorsal horn and divide into ascending and descending branches. The descending fibers and some of the ascending ones enter the gray matter of the dorsal horn within a few segments of their entrance and synapse with nerve cells in the posterior horns as well as with large ventral horn cells that subserve segmental reflexes. Some of the ascending fibers run uninterruptedly in the dorsal columns of the same side of the spinal cord, terminating in the gracile and cuneate nuclei in the upper cervical spinal cord and medulla (Fig. 8-5). The central axons of the primary sensory neurons are joined in the posterior columns by other secondary neurons whose cell bodies lie in the posterior horns of the spinal cord. The fibers in the posterior columns assume a medial position as new fibers from each successively higher root are added laterally,


Neurology_Adams

Neurology_Adams. whose cell bodies lie in the posterior horns of the spinal cord. The fibers in the posterior columns assume a medial position as new fibers from each successively higher root are added laterally, thereby creating somatotopic laminations (see Fig. 7-3).


Neurology_Adams

Neurology_Adams. Of the long ascending posterior column fibers, which are activated by mechanical stimuli of skin and subcutaneous tissues and by movement of joints, only about 25 percent (from the lumbar region) reach the gracile nuclei at the upper cervical cord. The remaining fibers send collaterals to, or terminate in, the dorsal horns of the spinal cord, at least in the cat (Davidoff). An estimated 20 percent of ascending posterior column fibers originate from cells in Rexed layers IV and V of the posterior horns (see Fig. 7-1) and convey impulses from low-threshold mechanoreceptors that are sensitive to hair movement, skin pressure, or noxious stimuli. There are also descending fibers in the posterior columns, including fibers from cells in the dorsal column nuclei.


Neurology_Adams

Neurology_Adams. The posterior columns contain a portion of the fibers for the sense of touch as well as the fibers mediating the senses of pressure, vibration, direction of movement and position of joints, which are also necessary for the integrative sensory experience of stereoesthesia—recognition of surface texture, shape, numbers, and figures written on the skin and two-point discrimination. The nerve cells of the nuclei gracilis and cuneatus and accessory cuneate nuclei give rise to a secondary afferent path, which crosses the midline in the medulla and ascends as the medial lemniscus to the posterior thalamus (Fig. 8-5). However, the fiber pathways in the posterior columns are not the sole mediators of proprioception in the spinal cord (see “Posterior [Dorsal] Column Syndrome” further on).


Neurology_Adams

Neurology_Adams. In addition to the well-defined posterior column pathways, there are cells in the more loosely structured “reticular” part of the dorsal column that receive secondary ascending fibers from the dorsal horns of the spinal cord and from ascending fibers in the posterolateral columns. These dorsal column fibers project to brainstem nuclei, cerebellum, and thalamic nuclei. Many other cells of the dorsal horn nuclei are interneurons, with both excitatory and inhibitory effects on local reflexes or on the primary ascending sensory neurons. The functions of many of the extrathalamic projections of dorsal column cells are unknown (Davidoff).


Neurology_Adams

Neurology_Adams. As described in the previous chapter, thinly myelinated or unmyelinated fibers, subserving mainly pain sensibility, but some sensitive to touch and pressure, enter the cord on the lateral aspect of the dorsal horn and synapse with dorsal horn cells, mainly within a segment or two of their point of entry into the cord. The dorsal horn cells, in turn, give rise to secondary sensory fibers, some of which may ascend ipsilaterally but most of which decussate and ascend in the spinothalamic tracts (see Figs. 7-1 and 7-2). Observations based on surgical interruption of the anterolateral funiculus indicate that fibers mediating touch and deep pressure occupy the ventromedial part (anterior spinothalamic tract). Also as remarked in Chap. 7, an ascending tract of secondary sensory axons lies in or medial to the descending corticospinal system.


Neurology_Adams

Neurology_Adams. After the posterior columns terminate in the gracile and cuneate nuclei of the rostral cervical cord and medulla, synapses are made with fibers that cross the midline and ascend to form the medial lemniscal tracts in the brainstem. The lemniscal system is situated in a paramedian position, changing orientation slightly at different levels of the brainstem, and joining the spinothalamic system in the rostral midbrain to terminate in the posterior thalamic nuclei (Fig. 8-5 and also Fig. 7-2).


Neurology_Adams

Neurology_Adams. Comparable to the peripheral nerves, the sensory cell bodies for touch, pressure, and pain lie in the gasserian ganglion. The pathways mediating cutaneous sensation from the face and head—especially touch, pain, and temperature—are conveyed to the brainstem by the trigeminal nerve. After entering the pons, the fibers subserving touch synapse in the principal trigeminal sensory nucleus and the secondary neurons cross and join the medial lemniscus on its transit to the thalamus. A specialized system for proprioception of mandibular (masseter) movement originates in muscle spindles but has cell bodies in the mesencephalic nucleus of the fifth nerve.


Neurology_Adams

Neurology_Adams. As discussed in the preceding chapter, the pain and temperature fibers of the trigeminal nerve turn caudally and run through the ipsilateral medulla as the descending spinal trigeminal tract, synapsing with the long, vertically oriented spinal trigeminal nucleus that lies beside the tract. Axons from the neurons of this nucleus cross the midline and ascend as the trigeminal quintothalamic tract (also termed, somewhat imprecisely, trigeminal lemniscus) along the medial side of the spinothalamic tract (see Figs. 7-2 and 8-5), of which it is the equivalent. There is a somatotopic organization of fibers for pain and temperature, but not touch, in the trigeminal nucleus, so that the central part of the face is represented most rostrally, and the peripheral portion, most caudally, giving rise to an “onion skin” pattern of sensory loss (see also Chap. 44).


Neurology_Adams

Neurology_Adams. The ventral posterior thalamic nucleus receives fibers from the medial lemniscal, spinothalamic, and trigeminal (fibers from the principal sensory and spinal trigeminal nuclei) tracts, and projects mainly to two somatosensory cortical areas. The first area (S1) corresponds to the post-central cortex or Brodmann areas 3, 1, and 2 (see Fig. 3-3). S1 afferents are derived primarily from the ventral posterolateral nucleus (VPL, the terminus of medial lemniscal and spinothalamic fibers) and the ventral posteromedial nucleus (VPM, the terminus of trigeminal fibers) and are distributed somatotopically, with the leg represented superomedially and the face inferolaterally (face and hand are juxtaposed). Figure 8-6 (“sensory homunculus”) shows the cortical representation of sensory information in the postcentral gyrus. As in the case of the motor representation (see also Fig. 3-4), a disproportionate area is devoted to localization in the fingers, lips, and face.


Neurology_Adams

Neurology_Adams. Electrical stimulation of this area yields sensations of tingling, numbness, and warmth in specific regions on the opposite side of the body. The information transmitted to S1 is tactile and proprioceptive, derived mainly from the dorsal column–medial lemniscus system and concerned mainly with sensory discrimination. The second somatosensory area (S2) lies on the upper bank of the sylvian fissure, adjacent to the insula. Localization of function is less discrete in S2 than in S1, but S2 is also organized somatotopically, with the face rostrally and the leg caudally. The sensations evoked by electrical stimulation of S2 are much the same as those of S1 but, in distinction to the latter, may be felt bilaterally.


Neurology_Adams

Neurology_Adams. Undoubtedly, the perception of sensory stimuli involves more of the cerebral cortex than the two discrete areas described above. Some sensory fibers probably project to the precentral gyrus and others to the superior parietal lobule. Moreover, S1 and S2 are not purely sensory in function; motor effects can be obtained by stimulating them electrically. It has been shown that sensory neurons in VPL, cuneate and gracile nuclei, and sensory neurons in the dorsal horns of the spinal cord all receive descending as well as ascending cortical projections. This reciprocal arrangement probably influences movement and the transmission and interpretation of some sensations as discussed in Chap. 7.


Neurology_Adams

Neurology_Adams. Because they are situated as way stations in a serial system, if the thalamus and subcortical projections are damaged, sensations such as pain, touch, pressure, and extremes of temperature do not reach consciousness. Damage to the sensory cortex allows some appreciation of contralateral sensory experience but degrades accurate localization, as well as the patient’s ability to make other fine sensory discriminations. This clinical application of these features is elaborated in the discussion of the sensory syndromes further on. From this brief account of the various channels of sensory information, one must conclude that at every level there is the possibility of feedback control from higher levels. Most external and some internal stimuli are highly complex and induce activity in more than one sensory system. In every system there is sufficient redundancy to allow lesser-used systems to compensate partially for the deficits incurred by disease.


Neurology_Adams

Neurology_Adams. Terminology of Sensory Signs and Symptoms A few terms require definition, as they are commonly encountered in discussions of sensation. Some of these, relating to pain, were mentioned in Chap. 7. Experimental data support the view that partially damaged touch, pressure, thermal, and pain fibers become hyperexcitable and generate ectopic impulses along their course, either spontaneously or in response to stimuli (Ochoa and Torebjork). These abnormal sensations are experienced as paresthesias, or dysesthesias if they are severe and distressing, as noted in Table 8-2. Another positive sensory symptom is allodynia, referring to a phenomenon in which a non-painful stimulus such as touch evokes pain.


Neurology_Adams

Neurology_Adams. Anesthesia refers to a complete loss and hypesthesia to a partial loss of all forms of sensation. Loss or impairment of specific cutaneous sensations may be indicated by an appropriate prefix or suffix, for example, thermoanesthesia or thermohypesthesia (loss and reduction in temperature sense), analgesia (loss of pain sense), hypalgesia (reduction in pain sensibility), tactile anesthesia, and pallanesthesia, or apallesthesia (loss of vibratory sense). The term hyperesthesia, as explained in Chap. 7, refers to an increased sensitivity to various stimuli and is usually used with respect to cutaneous sensation. It implies a heightened activity of the sensory apparatus. Under certain conditions (e.g., sunburn), there does appear to be an enhanced sensitivity of cutaneous receptors, but usually the presence of hyperesthesia betrays an underlying sensory defect. Careful testing will demonstrate an elevated threshold to tactile, painful, or thermal stimuli; but once the stimulus is


Neurology_Adams

Neurology_Adams. usually the presence of hyperesthesia betrays an underlying sensory defect. Careful testing will demonstrate an elevated threshold to tactile, painful, or thermal stimuli; but once the stimulus is perceived, it may have a severely painful or unpleasant quality (hyperpathia). Some clinicians use this last term to denote an exaggerated response to a painful stimulus (hyperalgesia which is subtly different from hyperpathia, denotes an abnormally painful reaction to a painful stimulus; see Table 8-2). In alloesthesia, or allesthesia, a tactile or painful stimulus delivered on the side of hemisensory loss is experienced in a corresponding area of the opposite side or at a distant site on the same side. This phenomenon is observed most frequently with right-sided putaminal lesions (usually hemorrhage) and with anterolateral lesions of the cervical spinal cord; it presumably depends on the existence of an uncrossed ipsilateral spinothalamic pathway (see the original studies of Ray and


Neurology_Adams

Neurology_Adams. hemorrhage) and with anterolateral lesions of the cervical spinal cord; it presumably depends on the existence of an uncrossed ipsilateral spinothalamic pathway (see the original studies of Ray and Wolff).


Neurology_Adams

Neurology_Adams. Most neurologists would agree that sensory testing is the most challenging part of the neurologic examination. For one thing, test procedures are relatively crude and are unlike the natural modes of stimulation with which the patient is familiar. It is also fair to say that few diagnoses are made solely on the basis of the sensory examination; more often the exercise serves to complement the remainder of the examination. There is often difficulty in evaluating the response to sensory stimuli, as it depends on the patient’s interpretation of sensory experiences. This, in turn, will depend on the patient’s general awareness and responsiveness and ability to cooperate, as well as degree of suggestibility. Children, by virtue of their simple and direct responses, are often better witnesses than more sophisticated individuals who are likely to analyze their experiences minutely and report small and insignificant differences in stimulus intensity.


Neurology_Adams

Neurology_Adams. Quite often, no objective sensory loss can be demonstrated despite symptoms that suggest the presence of such an abnormality. Only rarely does the opposite occur, in which one discovers a sensory deficit when there has been no complaint of sensory symptoms. Sensory symptoms such as paresthesias or dysesthesias may be generated from nerves not sufficiently diseased to reduce sensory function. Furthermore, loss of sensory function may be so mild and gradual as to pass unnoticed.


Neurology_Adams

Neurology_Adams. Before proceeding to sensory testing, the physician should question patients about changes in sensation; this poses particular problems. Patients may be confronted with derangements of sensation that are unlike anything they have previously experienced, and they have limited terms to describe what they feel. They may say that a limb feels “numb” and “dead” when in fact they mean that it is weak. Occasionally a loss of sensation is discovered almost accidentally, for example, by a lack of pain on touching an object hot enough to blister the skin or unawareness of articles of clothing and other objects in contact with the skin. Often, disease induces new and unnatural sensory experiences such as a band of tightness, a feeling of the feet being encased in cement, lancinating pains, an unnatural feeling when stroking the skin, a sensation as if walking on pebbles, and so on. Even adventitious muscle movements may be reported as a sensory experience akin to paresthesias or other


Neurology_Adams

Neurology_Adams. an unnatural feeling when stroking the skin, a sensation as if walking on pebbles, and so on. Even adventitious muscle movements may be reported as a sensory experience akin to paresthesias or other sensations.


Neurology_Adams

Neurology_Adams. If nerves, sensory roots, or spinal tracts are damaged or partially interrupted, the patient may complain of tingling or prickling feelings (“like Novocain” or like the feelings in a limb that has “fallen asleep,” the colloquialism for nerve compression), cramp-like sensations, or burning or cutting pain occurring either spontaneously or in response to stimulation.


Neurology_Adams

Neurology_Adams. The clinical description of a sensation may divulge the particular sensory fibers involved (see Table 8-1). It is known that stimulation of touch fibers gives rise to a sensation of tingling and buzzing; of muscle proprioceptors, to pseudocramp (the sensation of cramping without actual muscle contraction); of thermal fibers, to heat (including burning) and coldness; and of A-δ fibers, to prickling and pain. Paresthesia arising from ectopic discharges in large sensory fibers can be induced by nerve compression, hypocalcemia, hypomagnesemia, certain medications (niacin foremost among them), and diverse diseases of nerves. Band-like sensations on a limb or the trunk are the result of dysfunction in large sensory fibers, either in the periphery or their continuation in the posterior columns. Certain sensory symptoms suggest an anatomic location of nerve disease; for example, lancinating pains that radiate to the back or neck implicate root or, less often, sensory ganglion disease.


Neurology_Adams

Neurology_Adams. Persistent paresthesias incriminate a lesion involving sensory pathways in nerves, spinal cord, or higher structures. Most often, the large diameter, heavily myelinated fibers in the peripheral nerves or posterior columns are involved. Evanescent paresthesia, of course, is usually of no significance. Every person has had the experience of resting a limb on the ulnar, sciatic, or peroneal nerve and having the extremity “fall asleep.” This is because of compressive interruption of axonal transport and not of ischemia of the nerves or other structures of the limb as is commonly assumed. The hyperventilation of anxiety may cause paresthesia of the lips and hands (sometimes unilateral) from diminution of CO2 and thereby of ionized calcium; tetany may also occur, with carpopedal spasms. However, these sensory experiences are transient and should not be confused with the persistent, albeit sometimes fluctuating, paresthesias of structural disease of the nervous system. Severe acral and


Neurology_Adams

Neurology_Adams. these sensory experiences are transient and should not be confused with the persistent, albeit sometimes fluctuating, paresthesias of structural disease of the nervous system. Severe acral and peripheral paresthesias with perversion of hot and cold sensations are characteristic of certain neurotoxic shellfish poisonings (ciguatera) and other toxins, such as mercury.


Neurology_Adams

Neurology_Adams. Also worth comment are vibratory paresthesias, which we have encountered in only a handful of patients. One articulate physician described the sensation as a high-amplitude, low-frequency “buzz” that was distinctly different from the more common prickling paresthesia, burning, numbness, etc. We have the impression that these sensations are almost always a manifestation of central sensory disease, in one case probably attributable to the posterior columns and in another to cerebral disease. Beyond this, little is known about this symptom. Effect of Age on Sensory Function


Neurology_Adams

Neurology_Adams. Effect of Age on Sensory Function A matter of importance in the testing of sensation is the progressive impairment of sensory perception that occurs with advancing age. This requires that sensory thresholds, particularly in the feet and legs, be assessed in relation to age standards. The effect of aging is most evident in relation to vibratory sense, but proprioception, the perception of touch, and fast pain are also diminished with age. Sweating and vasomotor reflexes are reduced as well. These aging changes, which are discussed further in Chap. 28, are probably caused by neuronal loss in dorsal root ganglia and are reflected in a progressive depletion of fibers in the posterior columns. Receptors in the skin and special sense organs (taste, smell) also atrophy with age. On the other hand, it is too facile to attribute sensory loss to aging alone because it risks overlooking important disorders, some treatable. Testing of Sensory Function