Multimodal Therapy for Multimechanistic Pain

To a patient, pain is pain. But to clinicians, it is important to understand the underlying pain mechanisms in order to find the appropriate modalities for pain control.1

Pain can be divided into two broad categories: physiological (nociception, inflammation) and pathological (neuropathic).

Nociceptive pain occurs when there is an injury at the periphery (for example, hitting your thumb with a hammer). The local nociceptors send a signal back through the nervous system to the dorsal horn, which modulates and sends the signal upward via the spinal cord to the brain. The brain receives this message and “interprets” it, sending back a signal for pain. Nociceptive pain is an adaptive function in that it allows the body to recognize injuries and forces the cessation of actions that can further harm the body. Inflammatory pain and somatic pain are types of nociceptive pain. Nociceptive pain can persist and compels protection of the injured area until the tissue can heal.2

Nociceptive pain includes pain that originates from trauma, from joints and tissue (somatic pain), from internal organs (visceral), or from the inflammatory process. While these are all types of nociceptive pain, they may be perceived quite differently by the patient. Visceral pain, for example, is often dull, diffuse but can be quite severe, while somatic pain may be sharper and more localized.

Neuropathic pain, on the other hand, occurs when aberrant signaling from the nervous system travels to the brain and is interpreted as pain. Neuropathic pain syndromes can also amplify small events so that they are perceived by the brain as much more painful than would otherwise be the case.

Patients may have nociceptive or neuropathic pain but it is not uncommon to have nociceptive pain with a neuropathic component.3 This type of pain is called multimechanistic or multifactorial because there are two entirely separate mechanisms producing what the patient reports as pain. This has important clinical implications because treating just one part of the pain—for instance, the nociception—will not reduce the neuropathic component and vice versa.

In general, nociceptive pain is associated with a specific cause (for example, twisted ankle, broken arm), with the reported pain proportional to what a clinician would expect. If asked to describe nociceptive pain, patients might use words such as throbbing, deep, stabbing, or dull. Neuropathic pain, on the other hand, is more likely to be described as shooting, “electrical,” shocking and may be associated with numbness or a sensation of “pins and needles.” Neuropathic pain can also have a sudden onset and overtake a patient without warning. It is important to realize here that there can be considerable overlap in descriptions and not all patients will describe neuropathic or nociceptive pain in the same way—these are to be taken as helpful generalizations.

Many pain scales ask patients to rate the pain in terms of intensity or how bad it feels.4 While pain intensity is an important metric and one that patients readily understand, it does not necessarily help differentiate different pain mechanisms. It is important to ask patients about the quality and characteristics of pain to better understand if the pain is nociceptive, neuropathic, or a combination.

In addition to these types of pain, clinicians should also consider whether pain is acute or chronic.

Some clinicians also add a third category of “subacute” pain between these two. While it is often handy to describe acute pain as pain of short duration and chronic pain as pain that lasts three to six months or more, this rule of thumb obscures an important differentiation between acute and chronic pain. Chronic pain involves the process of central sensitization or aberrant neurosignaling that can lower the pain threshold.5 Acute pain may transition into chronic pain in a process known as “windup” or central sensitization. In this process, aberrant nervous system signaling causes the patient to feel more pain than is appropriate to the situation. Chronic pain is maladaptive and may become dissociated from its original cause.

In general, acute pain is specific—it is localized and the patient can usually explain what happened to cause the pain. Chronic pain is more diffuse, vague, and even migratory and the patient may no longer have any idea what caused the pain originally. Chronic nociceptive pain syndromes include headaches, arthritis, and fibromyalgia.

Short Glossary of Pain Types

Pain Type Mechanism Broad Category
Acute pain Pain of short duration Nociceptive
Chronic pain Pain of longer duration that involves central sensitization Neuropathic pain which may also have nociceptive component
Inflammatory pain Inflammatory process Nociceptive
Neuropathic pain Aberrant signaling in the nervous system, may amplify pain signals (lowering pain threshold) Neuropathic
Somatic pain Pain associated with skin, muscle, joints, or tissue. Pain is detected by nerves in the skin. Nociceptive
Visceral pain Pain from the internal organs Nociceptive

When treating pain, it is important to recognize that different pain mechanisms respond to different treatments. Inflammatory pain, for example, may benefit from reducing the inflammatory process. Nociceptive pain often benefits from pain relievers such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), or opioids. These pharmacological treatments have little effect on neuropathic pain, which may require adjuvant therapy such as anticonvulsants (for example, pregabalin). Patients may also benefit from muscle relaxants and antidepressants.

Multimodal pain therapy combines pharmacological and nonpharmacological approaches to pain control with complementary mechanisms of action to address all relevant pain mechanisms. Manipulation in combination with topical analgesics such as OxyRub PRO benefit somatic pain syndromes, such as sprains, tendinitis, and arthritis.

This highlights the importance of including nonpharmacological approaches along with drug therapy when combining pain therapies for the patient’s pain treatment. Nonpharmacological therapy may include spinal manipulations, massage, exercise, laser or magnet therapy, lifestyle modifications, occupational therapy, and complementary and alternative medicine (CAM). A patient with multimechanistic pain may benefit from a multimodal regimen that combines chiropractic, occupational therapy, a topical analgesic and occasional NSAIDs to help reduce inflammation. Remember, it is important to address the pain but it is equally as important to decrease suffering which manifests as decreases in quality of life, functionality, and activities of daily living.


  1. Rafiq S, Steinbruchel DA, Wanscher MJ, et al. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial. Journal of cardiothoracic surgery. 2014;9:52.
  2. Fong A, Schug SA. Pathophysiology of pain: a practical primer. Plastic and reconstructive surgery. 2014;134(4 Suppl 2):8S-14S.
  3. Fishbain DA, Lewis JE, Cutler R, Cole B, Rosomoff HL, Rosomoff RS. Can the neuropathic pain scale discriminate between non-neuropathic and neuropathic pain? Pain medicine (Malden, Mass). 2008;9(2):149-160.
  4. Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. Journal of clinical nursing. 2005;14(7):798-804.
  5. Pergolizzi JV, Jr., Raffa RB, Taylor R, Jr. Treating acute pain in light of the chronification of pain. Pain management nursing : official journal of the American Society of Pain Management Nurses. 2014;15(1):380-390.


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