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Pre- and post-operative pain are among the most difficult problems to manage in dental practice. There are various factors that could influence these conditions: from the patient’s susceptibility to the clinical practice performed. However, an adequate management of both allows to considerably improve the patient’s compliance and, at the same time, the satisfaction of the latter. All articles and reviews considered in this brief review, were searched on the online platform of scientific reading sites such as PubMed and Medline, selecting the most current ones, up to January 2022. Considering the keywords “Analgesic drugs”, “dentistry” AND “dental pain”, randomized controlled trials (RCTs), prospective studies, observational studies, reviews, and retrospective studies were considered. The aim of this narrative review is to describe the several therapeutic techniques allowed to reduction of pre- and post-operative pain during clinical dental practice, so as to be able to outline in a linear and concise way some brief clinical guidelines that can be easily consulted.
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1971-1441
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en
Matteo  Nagni
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Analgesic drugs in dentistry: a narrative review
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Matteo  Nagni
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Dental School, Vita-Salute San Raffaele University, Milan, Italy and Department of Dentistry, IRCCS San Raffaele Hospital, Milan, Italy
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drug-dynamics
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Analgesic drugs in dentistry: a narrative review
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                                                                                                       Case report


Analgesic drugs in dentistry: a narrative review




Bianca D’Orto*                                              experience associated with actual or potential tissue
Carmen Baldi*                                               damage”.
Vanessa Bonafede*                                           Depending on the pathogenesis, pain can be classified
Andrea Pacifici°                                            into four main categories:
Imma Ianniceli*                                             1. nociceptive, transient pain in response to a peripheral
Matteo Nagni*                                                   stimulation.
                                                            2. inflammatory, instantaneous pain related to a painful
*
  Dental School, Vita-Salute San Raffaele University, Mi-       hypersensitivity resulting from inflammatory tissue
lan, Italy and Department of Dentistry, IRCCS San Raf-          damage. Depending on the site involved, it is subdi-
faele Hospital, Milan, Italy                                    vided into:
°Libero Professionista PhD Sapienza University of               • superficial somatic (skin or mucous membranes)
Rome, Rome, Italy.                                              • deep somatic (muscles, bones, joints)
                                                                • visceral (internal viscera)
                                                            3. neuropathic, pain occurring in the peripheral or central
                                                                nervous system, in the absence of a nociceptive insult.
Abstract                                                    4. psychogenic, pain caused by an abnormal interpreta-
Pre- and post-operative pain are among the most dif-            tion of perceptual messages, in the absence of verifi-
ficult problems to manage in dental practice. There             able damage to the nervous system.
are various factors that could influence these condi-
tions: from the patient’s susceptibility to the clinical    Biochemical basis of dental pain
practice performed. However, an adequate manage-
ment of both allows to considerably improve the             Dental pain is predominantly inflammatory and is caused
patient’s compliance and, at the same time, the sat-        by the release of chemical mediators from tissue cells,
isfaction of the latter. All articles and reviews consid-   mediators that are referred to as ‘prostanoids’.
ered in this brief review, were searched on the online      This category of chemical mediators, which includes a
platform of scientific reading sites such as PubMed         whole series of molecules such as histamine, bradykinin,
and Medline, selecting the most current ones, up to         thromboxane A2, prostaglandins (PGE2, PGD2, PGF2α),
January 2022. Considering the keywords “Analgesic           and substance P, is capable of overcoming cell mem-
drugs”, “dentistry” AND “dental pain”, randomized           brane defences so that it can interact with specific high-
controlled trials (RCTs), prospective studies, obser-       affinity protein receptors located at nerve endings (with a
vational studies, reviews, and retrospective studies        greater prevalence in C a-myelin fibres).
were considered.                                            As a result of trauma and surgery, prostanoids are re-
The aim of this narrative review is to describe the         leased into soft tissue, hard and connective tissue.
several therapeutic techniques allowed to reduction         Histamine, bradykinin and substance P sensitise nerve
of pre- and post-operative pain during clinical dental      endings, leading to oedema formation during the early
practice, so as to be able to outline in a linear and       stages of inflammation; prostaglandins, on the other
concise way some brief clinical guidelines that can         hand, protract pain sensation. Thus, it can be argued
be easily consulted.                                        that the main contributors to primary hyperalgesia (i.e.
                                                            an increased response to a painful stimulus) are pros-
                                                            tanoids, fatty acids derived from arachidonic acid, a
Keywords: analgesic drugs, dentistry, dental pain,          constituent part of membrane phospholipids. Phospho-
drug-kinetics, drug-dynamics.                               lipase A2, after being released from membranes follow-
                                                            ing trauma, converts arachidonic acid into PGH2, which
                                                            leads to the release of prostanoids through the activity
INTRODUCTION                                                of a particular enzyme, COX-2 (type 2 cyclooxygenase).
                                                            COX-2 is inhibited non-selectively by non-steroidal anal-
Pre- and post-operative pain management appears to be       gesic drugs (NSAIDs).
one of the main issues that dentists have to deal with in
their daily practice. To undergo dental treatment without
                                                            WHO Analgesic Scale
pain is the patient’s main wish.
IASP (international association for the study of pain)      However, pain is generally identified as a subjective no-
defined pain as “an unpleasant sensory and emotional        ciceptive sensation, which is why it is not easy for the



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     Analgesic drugs in dentistry: a narrative review

     clinician to quantify and localise the pain stimulus. To      Corticosteroids
     this end, the WHO has developed an analgesic pain             Corticosteroids, also called cortico-adrenal hormones or
     scale, which is a classification of pain from one to ten      corticoids, are a group of steroid hormones synthesised
     according to the nociceptive sensation experienced by         in the cortical of the adrenal gland. They can be divided
     the patient, where one is the minimum pain and ten is         into three categories: glucocorticoids, mineralocorticoids
     the maximum pain. It is a very useful and validated scale     and sex hormones.
     and represents a guideline for pain therapy in dentistry.     Corticosteroids cause important anti-inflammatory ef-
     Thus, the choice of drug will be related to the mecha-        fects mainly through a reduction in capillary perme-
     nism of action and the potency of the pain.                   ability. The anti-inflammatory effect of glucocorticoids
     Analgesics are more effective in preventing the onset of      (cortisol, prednisone, etc.) is mostly mediated by an
     pain than in relieving existing pain, as long as they are     inhibition of the transcription of genes that regulate the
     administered regularly.                                       production of most inflammatory cytokines and type 2
                                                                   cyclo-oxygenase.
     MATERIALS AND METHODS                                         The most widely used in dentistry are triamcinolone, be-
                                                                   tamethasone and dexamethasone, which have half-lives
     All articles and reviews considering the topic of pain
                                                                   of 24-48 hours, 36-54 hours and 36-54 hours respectively.
     management in dentistry were searched on the online
                                                                   The effectiveness of synthetic corticosteroids in oral
     platform of scientific reading sites such as PubMed and
                                                                   surgery is still controversial, as there are no protocols
     Medline, selecting the most current ones, up to Janu-
                                                                   universally accepted by the international scientific com-
     ary 2022, including any language. Considering the key-
                                                                   munity.
     words “Analgesic drugs”, “dentistry” AND “dental pain”,
                                                                   However, the active ingredients most commonly used in
     randomized controlled trials (RCTs), prospective stud-
                                                                   oral surgery and their respective dosages are:
     ies, observational studies, reviews, and retrospective
                                                                   • Methylprednisolone
     studies were considered. Textbooks relevant to the topic
                                                                        Dosage: (0.5-1 mg/kg/day) for a normal-weight adult
     were then examined, and the citations of each retrieved
                                                                        about 40 mg one hour before surgery (half-life 2.4-
     article and those of reviews and expert opinions were
                                                                        3.5 hours) and after 12 hours. Same dosage every
     examined to include as much knowledge as possible.
                                                                        12 hours on subsequent days for no more than 24-48
                                                                        hours to avoid cortico-adrenal inhibition.
     LITERATURE REVIEW ON ANALGESIC                                • Dexamethasone
                                                                        Anti-inflammatory and anti-reactive activity 8-10
     DRUGS IN DENTISTRY
                                                                        times greater than prednisolone.
                                                                        Dosage: 8-16 mg dexamethasone one hour before
     Pharmacological types
                                                                        surgery and 8-16 mg every six hours for no more
     The analgesics used in dentistry are numerous and be-              than 24-48 hours to avoid cortico-adrenal inhibition.
     long to different categories; therefore, their use must be    However, even these substances are not free of various
     thoughtful and specific to the individual clinical case.      side effects, such as delayed wound healing, suppres-
                                                                   sion of adrenergic activity, hyperglycaemia, water-saline
                                                                   retention, hirsutism, acne, skin streaks, obesity, etc.
     Analgesic drugs with central mechanism                        All these side effects only become apparent when ad-
     of action                                                     ministered in large doses and over long periods of time.
     Paracetamol                                                   Single doses, on the other hand, are considered safe for
                                                                   healthy patients.
     Paracetamol or acetaminophen is an active ingredient
                                                                   Corticosteroids have therapeutic indications in dentistry
     with antipyretic and analgesic activity and has a weak
                                                                   in cases of:
     anti-inflammatory effect. It is considered a quite safe
                                                                   • non-herpetic mucosal lesions
     drug, so that its use, with the appropriate dosage, is also
                                                                   • nerve damage caused by surgery or trauma
     recommended for paediatric patients.
                                                                   • phlebitis
     From the chemical point of view, paracetamol is a de-
                                                                   • prophylaxis of preoperative surgical oedema
     rivative of para-aminophenol, obtained by acetylation
                                                                   • endodontic therapy (to relieve pain of peri-apical ori-
     of the latter. Paracetamol is now available by several
                                                                        gin)
     routes of administration:
                                                                   • prophylaxis of PONV (post-operative Nausea and
     •     oral
                                                                        Vomiting)
     •     rectal
                                                                   A meta-analysis by Markiewicz MR. et al. 2008, conduct-
     •     parenteral
                                                                   ed to evaluate the effect of corticosteroids in the control
     It has a synergistic action with NSAIDs and opioids.
                                                                   of lockjaw, oedema, and pain following lower third molar
     Recommended doses should be between 1000 and
                                                                   surgery, revealed that peri-operative administration of
     1500 mg.
                                                                   corticosteroids results in a reduction of post-operative
     The administration of paracetamol 1000 mg + codeine
                                                                   oedema and lockjaw.
     60 mg at the end of oral surgery reduces pain intensity
     and prolongs postoperative analgesia.
                                                                   Antibiotics
     Side effects may possibly include liver toxicity; kidney
                                                                   In dentistry, antibiotics are drugs prescribed daily by the
     damage; allergic reactions, on the other hand, are quite
                                                                   clinician for both prophylaxis and therapy against bacte-
     rare.
                                                                   rial infections. Despite this, the use of antibiotics as at-
     Doses of paracetamol of 500 mg + codeine 30 mg are
                                                                   tenuators of nociceptive stimuli is still a matter of debate
     indicated in less severe odontostomatological pain.
                                                                   in the scientific community today.



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B. D’Orto et al.

These drugs can be administered locally or systemi-               structure and action. NSAIDs commercially available are
cally. The systemic use of antibiotics, particularly after        about 25-30.
third-molar extraction, has been proposed by several              It is a category of drugs with a variety of effects, including
authors; however, this use does not seem to have any              antipyretic, anti-inflammatory and analgesic effects, and
additional effectiveness compared to local antibiotic             inhibition of platelet release and free radicals.
administration in preventing inflammatory oedema and              NSAIDs inhibit cyclooxygenase (COX), the enzyme re-
post-operative pain.                                              sponsible for converting arachidonic acid into prosta-
The use of antibiotics is indicated in the immuno-com-            glandins and thromboxanes.
promised patient or in cases where an active infection            About anti-inflammatory therapy, the identification of two
is present at the time of surgery. In such cases, the             different forms of cyclooxygenase has been of funda-
administration of an antibiotic can more effectively pre-         mental importance: COX 1 and COX 2.
vent the symptoms of infection and the resulting post-            The first is involved in general homeostasis and is found
operative pain.                                                   in most tissues and organs. COX 2, on the other hand, is
In dentistry, the prescription of antibiotics is empirical be-    not detected in tissues and only appears in response to
cause the dentist does not know which microorganisms              certain stimuli. Based on this difference, anti-inflamma-
                                                                  tory therapy has increasingly shifted to selective COX-2
are responsible for the infection, as samples from the
                                                                  inhibitors, referred to as coxib drugs.
root canal or peri-apical region are not commonly taken
                                                                  NSAIDs reduce the inflammatory response to surgical
and analysed. However, it has recently been seen that
                                                                  trauma, more or less intensely depending on the drug
the additional use of PACS (portable air cleaners) dur-
                                                                  used. The administration of NSAIDs with predominantly
ing dental practice can reduce the amount of bacterial
                                                                  anti-inflammatory activity should begin a few hours be-
micro-particles, thus being able to help the anti-bacterial
                                                                  fore dental surgery to prevent the inflammatory process.
action provided by antibiotics. The effectiveness of the
                                                                  The anti-platelet effects are mainly exerted at the site
PAC is confirmed from a microbiological point of view as          of the operation and on the gastric mucosa, leading, in
there is a reduction ranging from 69 to 80% in profes-            the latter case, to a haemorrhagic gastropathy pathol-
sional dental hygiene activity and from 62 to 66% during          ogy. The effects on the gastric mucosa consist of micro-
simple surgery activity.                                          bloodings which correlate with the duration of drug ther-
However, the most widely used antibiotic is amoxicillin,          apy. NSAID-induced gastric mucosal lesions are related
due to its sufficiently broad spectrum, efficacy, low inci-       to a combination of inhibition of gastric cyclooxygenase
dence of resistance, pharmacokinetic profile, tolerance,          and cytoprotective prostaglandin deficiency, resulting in
and dosage.                                                       altered mucosal blood flow.
The main antibiotics prescribed in the adult dental pa-           Those most at risk of gastropathy following the use of
tient have been summarised in Table 1.                            NSAIDs are:
Adverse effects of antibiotics, particularly of the beta-         • female patients over 60 years of age
lactam class (the most used drugs in dentistry) include           • patients on oral anticoagulant and/or antiplatelet
anaphylaxis, bacterial resistance, dysentery, or other al-             therapy
lergic reactions, especially skin rashes, which may occur         • patients with a history of gastric ulceration
during or days after treatment.                                   • poly-therapy patients
Macrolides, tetracyclines, erythromycin, clindamycin              • patients with previous NSAID intolerance
and ketoconazole are potentially toxic and particularly           Caution is required when using COXIBs in patients:
contra-indicated in patients with liver disease. In addi-         • diabetics
tion, tetracyclines may interfere with glycaemic control in       • hypertensives
diabetic patients.                                                • hyper-lipidemic
                                                                  • smokers
Analgesic drugs with peripheral mechanism                         NSAIDs are contraindicated in the presence of isch-
of action                                                         aemic heart disease and/or cerebrovascular disease;
                                                                  cardiac insufficiency; post-operative aorto-coronary by-
Non-steroidal analgesic drugs (NSAIDs)                            pass surgery.
They are called ‘non-steroidal’ because they do not have          For patients with swallowing difficulties, suspensions
a steroidal structure like that of cortico-steroid drugs.         and granules are preferable to solid tablets.
The category of non-steroidal anti-inflammatory drugs             Instead, an injection formulation is recommended in pa-
is extremely broad and includes many active ingredi-              tients refractory to oral administration and if an immedi-
ents that can be classified rendering to their chemical           ate analgesic effect is desired.


Table 1. Main antibiotics prescribed to the adult dental patient and dosage.

             ACTIVE PRINCIPLE                            DAILY DOSE                      MAINTENANCE DOSE
  Amoxicillin with or without clavulanic acid               1000 mg              500 mg every 8 h or 875 mg every 12 h
                   Clindamycin                               600 mg                          300 mg every 6 h
                Clarithromycin                               500 mg                         250 mg every 12 h
                   Azithromycin                              500 mg                         250 mg every 24 h
                Metronidazole                               1000 mg                          500 mg every 6 h




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     Analgesic drugs in dentistry: a narrative review

     In addition, acetyl salicylic acid, a widely used NSAID,          tion in clinical practice is lidocaine: the latter is used at a
     may interfere with glycaemic control in diabetic patients.        concentration of 2%, often in combination with adrena-
                                                                       line (a vasoconstrictor drug). The combination of these
     Opioids                                                           two compounds (lidocaine at 2% and adrenaline diluted
                                                                       1:100,000) is an effective preparation to obtain a pow-
     Opioids represent the treatment of choice for acute post-
                                                                       erful analgesic effect before dental procedures such as
     operative pain, both moderate and severe. Those most
     commonly used in dental practice include codeine and              fillings, apicoectomy, devitalizations, dental extractions,
     tramadol, which fall into the category of weak opioids.           or whatever.
     Morphine, and its related compounds, act as agonists              Nevertheless, it too is not free from side effects, such
     through a stereo-selective interaction with saturable             as possible mucosal reactions, skin rashes, and even
     membrane receptors, which are unevenly distributed                anaphylactic shock, although this latter reaction occurs
     throughout the central nervous system.                            in people allergic to lidocaine, a condition extremely rare.
     The prescription of opioids may be indicated in acute or          Local anaesthetics may be toxic in the event of over-
     chronic pain because of their obvious analgesic effects;          dose, or in the event of incorrect intravascular injection.
     however, they do not exempt significant risks such as             Toxic effects on the cardiovascular system are manifest-
     respiratory depression, altered mental status, nausea,            ed by a decrease in blood pressure, up to and includ-
     vomiting, pruritus, constipation, urinary retention and           ing ventricular fibrillation, an extremely serious but very
     slowed bowel movement. Moreover, the main unfavour-               sporadic event.
     able effects seem to be dose-dependent.                           A further adverse reaction to local anaesthetics is met-
     The administration of opioids by the dentist in the pres-         hemoglobinemia, the oxidation of haemoglobin from the
     ence of chronic pain, particularly if the pathology is un-        ferrous to the ferric state, which can cause cyanosis in
     known, must be supported by an additional approach                fetus. This is particularly attributable to prilocaine and
     with pain specialists.                                            benzocaine; for this reason, the FDA advises against the
                                                                       use of these drugs in pregnancy.
     Local anaesthetics                                                Anaesthetics with and without vasoconstrictors are sum-
                                                                       marized in Table 2, with the corresponding maximum
     This is a heterogeneous group of active ingredients
                                                                       dosage.
     which, acting at different sites and with different mecha-
     nisms of action, induce anaesthesia.
     The term “local anaesthesia” refers to the loss of sensa-         Post-operative pain management
     tion in a specific area. These drugs can be used either           A preliminary estimate of postoperative pain is useful for
     topically (creams, gels) or infiltrative (plexic or truncular     the establishment of a predefined analgesic scheme, us-
     anaesthesia).                                                     ing non-opioid analgesics administered singly or in com-
     However, it is important to emphasise that local anaes-           bination, possibly with opioid drugs.
     thetics do not induce analgesia because, unlike anti-in-          • In the presence of mild pain, an administration of:
     flammatory drugs, they do not inhibit the synthesis and              - Ibuprofen 200/400 mg every 4/6 hours as needed.
     release of pain mediators, nor do they interact with pain         • In the case of mild to moderate pain, the administra-
     receptors.                                                           tion of:
     It is known, however, that long-acting local anaesthetics            - Ibuprofen should be about 400/600 mg every 6
     prolong the duration of post-operative analgesia, espe-              hours at regular intervals for the first 24 hours; there-
     cially in more complex implant-prosthetic rehabilitations.           after as required.
     Bupivacaine and ropivacaine are useful for this purpose.          • Then, in the presence of moderate-to-severe pain, the
     Bupivacaine is widely used in oral surgery mainly for soft           administration of: Ibuprofen 400/600 mg combined
     tissue infiltration, prolonging post-operative analgesia,            with paracetamol 500 mg every 6 hours at regular
     especially when combined with adrenaline; this anaes-                intervals for the first 24 hours; thereafter as needed.
     thetic drug is very effective in soft tissue infiltration after   • Finally, in the presence of severe pain, an administra-
     oral surgery (such as extraction of third molars included)           tion of:
     and in implantology. Bupivacaine and ropivacaine, which              - Ibuprofen 400/600 mg combined with paracetamol
     are long-acting local anaesthetics, should only be used              500 mg and hydrocodone 10 mg every 6 hours at reg-
     in the adult population, as they may cause undesirable               ular intervals for the first 24/48 hours; then ibuprofen
     reactions in children and the disabled.                              400/600 mg combined with paracetamol 500 mg as
     Among the local anaesthetics that have a great valida-               required.




     Table 2. Posology of main anaesthetics prescribed in dentistry.

                                        MAXIMUM DOSE WITH                               MAXIMUM DOSE WITHOUT
                                        VASOCONSTRICTOR                                 VASOCONSTRICTOR
      LIDOCAINE 2%                      7 mg/kg                                         4,4 mg/kg

      ARTICAINE 4%                      7 mg/kg (adult)                                 /
                                        5 mg/kg (child)
      MEPIVACAINE                       2% 6,6 mg/kg                                    3% 4,4 mg/kg




26                                                                                                          10.59987/ads/2023.4.23-29
B. D’Orto et al.

Injection formulations for increasing sever-                             Clin Anaesthesiol. 2005 Jun;19(2):247-68. doi: 10.1016/j.
                                                                         bpa.2004.12.003.
ity of pain                                                          •   Chhabra A, Nidhi C, Jain A. Knowledge, attitudes and prac-
• Paracetamol                                                            tice preference regarding drug prescriptions of resident
  Vials: 1,000 mg                                                        dental doctors: A quantitative study. Int J Risk Saf Med.
  Dosage: 1,000-2,000 mg every 6-8 hours                                 2019;30(2):91-100. doi: 10.3233/JRS-180021.
                                                                     •   Chung MK. A virtual case-based learning module for pain in
  (Maximum daily dose 8,000 mg).
                                                                         dentistry. J Dent Educ. 2021 Dec;85 Suppl 3:1928-1929. doi:
• Tramadol                                                               10.1002/jdd.12567.
  Vials: 100 mg                                                      •   Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH,
  Dosage: 100 mg every 6-8 hours.                                        Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, Ec-
• Pentazocine lactate                                                    cleston C, Kalso E, Bennett DL, Dworkin RH, Raja SN. Neu-
  Vials: 30 mg                                                           ropathic pain. Nat Rev Dis Primers. 2017 Feb 16;3:17002.
                                                                         doi: 10.1038/nrdp.2017.2.
  Dosage: 30 mg every 3-4 hours.
                                                                     •   Crincoli V, Favia G, Limongelli L, Tempesta A, Brienza N.
                                                                         The effectiveness of ropivacaine and mepivacaine in the
CONCLUSION                                                               post-operative pain after third molar surgery. Int J Med Sci
In the treatment of pain in dentistry, the clinician must                2015; 12:862-866.15.
                                                                     •   D’Orto, B.; Polizzi, E.; Nagni, M.; Tetè, G.; Capparè, P. Full
consider several key points to establish the most suitable
                                                                         Arch Implant-Prosthetic Rehabilitation in Patients with Type
and appropriate therapy for the clinical case in question:               I Diabetes Mellitus: Retrospective Clinical Study with 10
•     drug-kinetics, drug-dynamics and drug-genetics of                  Year Follow-Up. Int. J. Environ. Res. Public Health2022, 19,
      the therapeutic medium used                                        11735. https://doi.org/10.3390/ijerph191811735.
•     effective, and possibly immediate, analgesic treat-            •   Daniel E, Becker DDS. Basic and clinical Pharmacology of
      ment                                                               glucocorticoids. Anesth Prog.2013;60:25-32.
                                                                     •   Drugs and Lactation Database (LactMed) [Internet]. Bethes-
•     elimination of the source of the painful stimulus pos-
                                                                         da (MD): National Library of Medicine (US); 2006-. Dexa-
      sible, through dental procedures                                   methasone. 2021 Nov 15.
•     assess the possible adverse effects of each indi-              •   Dumford D 3rd, Skalweit MJ. Antibiotic-Resistant Infections
      vidual drug class                                                  and Treatment Challenges in the Immunocompromised Host:
•     analysing and assessing the medical and dental                     An Update. Infect Dis Clin North Am. 2020 Dec;34(4):821-
      history of the individual patient before any drug                  847. doi: 10.1016/j.idc.2020.08.005.
                                                                     •   Edited by A. The WHO analgesic ladder and weak opioids
      therapy is initiated
                                                                         and weak opioids [WHO analgesic pain ladder and weak
•     favouring the use of NSAIDs over opioids.                          opioids]. Assist Inferm Ric. 2016 Jan-Mar;35(1):36-42. En-
It is therefore of fundamental importance to be able to                  glish. doi: 10.1702/2228.24020.
establish and understand the patient’s requests to anal-             •   Ferrari Cagidiaco, E., Carboncini, F., Parrini, S., Doldo, T.,
yse the degree and type of pain that the patient is suffer-              Nagni, M., Nuti, N., & Ferrari, M. (2018). Functional implant
ing; this will allow the determination of adequate analge-               prosthodontic score of a one-year prospective study on
                                                                         three different connections for single-implant restorations.
sia to reduce the nociceptive sensation before the dental
                                                                         Journal of Osseointegration, 10(4), 130-135. doi:10.23805/
procedure is performed.                                                  JO.2018.10.04.04.
                                                                     •   Fracon RN, Teófilo JM, Satin RB, Lamano T. Prostaglan-
                                                                         dins and bone: potential risks and benefits related to the
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