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Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms. PERSPECTIVE: This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The naturally occurring cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPM) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products' growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

This systematic review investigated the effectiveness and safety of botulinum toxin type A (BTX-A) for painful temporomandibular disorders. We searched for randomized controlled trials (RCTs) in 10 databases, from inception to February 12, 2019 (MEDLINE, EMBASE, CENTRAL, LILACS, BBO, Web of Science, Scopus, ClinicalTrials.gov, WHO and OpenGrey). We included 12 RCTs that compared BTX-A versus inactive or active interventions. BTX-A was slightly more effective than placebo for pain reduction at 1 month: mean difference -1.74 points (0-10 scale), 95% confidence interval -2.94 to -.54, 3 RCTs, 60 participants, I-square (I 2 ) = 0%. However, there were no significant differences at 3 and 6 months. BTX-A was similar to no treatment for pain reduction at 3 and 6 months. BTX-A was more effective than conventional treatment and low-level laser therapy for pain reduction at 1, 6, and 12 months, but less effective than facial manipulation for pain reduction at 3 months. BTX-A was not associated with a significant increase in the risk of adverse events. The quality of the evidence was low, and results are insufficient to support the use of BTX-A for painful temporomandibular disorders. High-quality RCTs are needed to increase confidence in effect estimates. PERSPECTIVE: BTX-A for painful temporomandibular disorders appears to be well tolerated. For pain reduction, BTX-A is slightly more effective than placebo only at 1 month; conventional treatment and low-level laser at 1, 6, and 12 months. Low-quality evidence limits the applicability of these findings and precludes recommendations for practice., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

This study investigated the antinociceptive effects of (S)-(-)-perillyl alcohol (PA) on orofacial nociception in Swiss male mice using formalin-, capsaicin-, and glutamate-induced pain tests. For each test, eight animals per group were pre-treated intraperitoneally by a blinded investigator with PA (50 or 75mg/kg), morphine, or vehicle (saline+0.2% Tween 80). The treatment was performed before the induction of orofacial nociception by injecting formalin, capsaicin, or glutamate solution into the right area of the upper lip. The orofacial nociceptive behaviour was timed in all tests by an investigator who was blinded to the treatments. The statistical analysis was performed using confidence intervals (CI), the effect size, and power. PA blocked the orofacial nociceptive behaviour at both doses tested (P<0.05) similarly to morphine (P>0.05), in all tests. The effect size was high in the phase 1 formalin test for 50mg/kg PA (95% CI 0.48-2.31, power 84.6%) and 75mg/kg PA (95% CI 0.82-2.76, power 96.2%), in phase 2 for 75mg/kg PA (95% CI 0.44-2.26, power 82.3%), and in the glutamate test for 75mg/kg PA (95% CI 1.11-3.16, power 99.2%). These findings show strong evidence for the antinociceptive properties of PA in the orofacial region., (Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The main objective of this retrospective review was to analyze the clinical outcomes following the use of botulinum toxin (onabotulinumtoxinA, Botox) injections to relieve the symptoms of chronic temporomandibular disorders (TMD). Seventy-one patients with a diagnosis of TMD (according to the RDC/TMD international consortium) associated with or without bruxism and refractory to conventional treatment (e.g. oral appliances, physiotherapy, etc.) received Botox injections into the temporalis and masseter muscles. Subjective responses to Botox were categorized as 'beneficial' or 'not beneficial', as patient-reported outcomes based on the subjective reduction in pain and/or improvement in function. Fifty-five of the 71 subjects (77%) reported beneficial effects with Botox. Subjects with a concomitant bruxism diagnosis reported significant improvement over subjects without bruxism (87% vs. 67%; P=0.042). Subjects with stress-related psychiatric comorbidities and bruxism had a significantly higher benefit than those with stress-related psychiatric comorbidities alone (P=0.027). Patients reported less improvement if the time between the initial Botox injection and follow-up was less than an average of 5 weeks, compared to an average follow-up of 5-10 weeks (P=0.009). The subgroup TMD diagnosis and time interval post-injection are important predictors of patient-reported beneficial outcomes., (Published by Elsevier Ltd.)

Our aim was to find out whether pain was better controlled if morphine or tramadol was injected intra-articularly after arthrocentesis with Ringer's lactate in patients with painful temporomandibular joints (TMJ). This placebo-controlled, double-blind study involved 30 patients who had not responded to conservative treatment and who were divided randomly into 3 groups of 10 patients each. All patients had arthrocentesis, and the drugs were given as intra-articular injections immediately after the procedure. One group was give 5% Ringer's lactate 1ml, the second morphine 1mg, and the third tramadol 50mg. Visual analogue scales (VAS) for pain were recorded at maximum mouth opening and at rest before intra-articular injection and after 15 and 30min; at 1, 2, 3, 8, 12, 24, 36 and 48h; and at 1, 3, and 6 monthly follow-up. The mean (SD) VAS decreased from 6.90 (1.45) to 2.6 (2.5) in the control group, from 7.30 (1.64) to 1.20 (0.79) in the morphine group (p=0.005), and from 7.10 (1.73) to 1.50 (1.78) in the tramadol group (p=0.005). We conclude that morphine given by intra-articular injection after arthrocentesis gives a significant, sustained (6 months) improvement in pain relief compared with simple arthrocentesis alone. The effect was similar with tramadol except that it was shorter lived., (Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Osteoid osteoma is a rare benign osseous neoplasm which rarely affects the jaws. It is more common in long bones which can lead to postural scoliosis. The clinical characteristic feature of this tumour is the unexplained pain that is relieved by the intake of analgesics. Histologically it is characterized by the formation of central nidus with surrounding sclerotic bone. The diagnostic dilemma in this case report is aggravated by its unusual association with the teeth. The use of CT scanning is advised to distinguish from other odontogenic tumours. Treatment for this tumour is surgical removal or excisional biopsy to avoid recurrence and progression to malignant changes., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Orofacial pain is a common complaint with multiple diagnoses. There is controversy about the effectiveness of antidepressants for the management of orofacial pain disorders. In order to be able to make a best evidence choice between available antidepressants for the treatment of orofacial pain, a systematic review was conducted of existing randomized controlled trials of antidepressants. Trials were identified from the Pubmed database up to March 2012, from references in retrieved reports and from references in review articles. Six articles were found and included in this review. Four studies were randomized placebo-controlled trials and two studies were randomized active-controlled trials. Two independent investigators reviewed these articles using a 15-item checklist. All six trials were of high quality according to the 15-item criteria. Nevertheless there was limited evidence to support the effectiveness of antidepressants in orofacial pain disorders, because of the heterogeneity of treatment modalities and the low number of randomized controlled trials per diagnose. More randomized controlled trials are needed to come to a firm conclusion for the use of antidepressants for orofacial pain disorders., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: The orofacial formalin test is established in rats and was recently transferred to mice. The aim of this study was to determine the ideal formalin concentration for testing analgesic drugs, to examine alternatives for the assessment of nociceptive and non-nociceptive behavior as well as the effects of morphine and age on formalin-induced nociception. Formalin (.5, 1, 2.5, 5, 7.5, 10, and 15%) was injected into the vibrissa of mice. The cumulative nociceptive behavior was measured as well as nociceptive and non-nociceptive behavior based on a score that was recorded over a 5-second observation period once per minute. We also examined the effects of morphine on the nociceptive response induced by 2.5% formalin. Age-dependent differences were tested in the third part of the experiment. NONMEM was used to model the pharmacodynamic effects of formalin and morphine. Injection of formalin lead to a concentration-dependent increase in cumulative nociceptive behavior ratings as well as the specific nociceptive behavior 3 of scratching injection site with hindpaw (score 3). The formalin concentrations that lead to 50% of the maximum effect were 2.6 and 3.3%, respectively, for the continuous rating method and the scoring method. Morphine dose dependently suppressed the nociceptive behavior and the number of score 3 ratings of the nociceptive behavior. Age differences in behavior could not be detected by either analytic method., Perspective: To improve the existing behavioral nociceptive assay for pain processed by the trigeminal system, we determined an ideal formalin concentration for the orofacial formalin test in mice, evaluated alternative timesaving analysis approaches, and investigated effects of morphine and age on formalin-induced nociception., (Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA-injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury., Perspective: Central sensitization is a concern in many craniofacial pain conditions. In this project, we utilize a conjugate of substance P and the catalytic subunit of cholera toxin to induce central sensitization in the nucleus caudalis of rodents. The data indicate that the injected animals become hypersensitive in the face., (Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Botulinum toxin (BTX) is a bacterial toxin that could be used as a medicine. Clinical applications of BTX have been expanding over the last 30 years and novel applications reported. Its mechanism of inhibiting acetylcholine release at neuromuscular junctions following local injection is unique for the treatment of facial wrinkles. Other dose-dependent anti-neuroinflammatory effects and vascular modulating properties have extended its spectrum of applications. Conditions such as temporomandibular joint disorders, sialorrhea, headache and neuropathic facial pain, muscle movement disorders, and facial nerve palsy could also be treated with this drug. Further applications of BTX are likely to be developed. This paper reviews the established and emerging applications of BTX in the field of oral and maxillofacial surgery. An overview of the pharmacology, toxicity and preparations of the agent is given.

Unlabelled: Few drugs are registered for treatment of neuropathic facial pain (NFP), and not much is known about treatment choices for NFP in daily practice. Patients with NFP were identified in the IPCI-database with longitudinal electronic general practitioner (GP) records. We described prescription patterns of pain medication following first symptoms. Off-label, off-guideline use, failure and reasons for failure were assessed. Failure was defined as treatment switch, exacerbation, adverse event, or invasive treatment for NFP. Of 203 NFP cases, 160 (79%) received pharmacological pain treatment. Most patients (90%) were initially treated by a GP with anti-epileptic drugs (55%) or NSAIDs (16%) as monotherapy. The median treatment delay was 0 days (range 0 to 2,478 days). Adverse events were experienced by 16 (10%) of patients. Sixty-two percent of first prescriptions were in adherence to guidelines and 59% were considered on-label while 34% of prescriptions were both off-label and off-guideline. Of the first therapy, 38% failed within 3 months. The median duration until failure was 251 days. General practitioners usually are the first to treat NFP. They usually prescribe drugs licensed for NFP and according to guidelines, but the extent of off-label use is substantial. Initial treatment often failed within a short period after starting therapy., Perspective: This drug-utilization study describes the pharmacological treatment of different forms of neuropathic facial pain in daily practice. Although treatment is mostly initiated rapidly by general practitioners in a correct way, it often contains off-label or off-guideline medication. Failure of the initial treatment is common and occurs rapidly as well., (Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: This study examined the occurrence of alcohol use to manage pain in community-dwelling adults with tooth pain, jaw joint/face pain, and arthritis. Race/ethnicity, sex, and age were examined to determine their associations with alcohol use for pain. Community-dwelling adults from South Florida with tooth pain (n = 1,767), jaw joint/face pain (n = 1,199), or arthritis pain (n = 1,355) completed a structured telephone interview. Logistic regression models indicted that, similar to population rates, nonHispanic whites and males were the most likely to use alcohol to manage pain. In addition, alcohol use for pain was highest in younger adults. Individuals who self-managed oral pain with alcohol were more likely to use prescription and over-the-counter pain medications, but this association was not found for arthritis. Additional characteristics of individuals who self-medicated regardless of pain condition included greater pain frequency, depression, and higher levels of education. Being married was protective against the use of alcohol to manage pain symptoms. Use of alcohol for pain should be assessed during treatment evaluation so that physicians and other health care providers are aware of their patient's concomitant use of alcohol and pain medication, assess for psychosocial impairment, and make the appropriate referrals and adjustment to treatment., Perspective: Self-medication of pain with alcohol is most common among younger nonHispanic white males and associated with pain frequency, depression, and use of pain medications. Alcohol use for pain needs to be assessed so that health care providers can make appropriate referrals and adjustments to treatment.

The management of temporomandibular joint (TMJ) disorders in secondary care has progressed through the 1990s from a condition dealt with by generalists to one with an increasing number of surgeons with a subspecialist interest. Within this latter group there is a subgroup of those with a specific training towards joint replacement surgery. Increasingly patients who previously had surgery for pain are being managed with non-surgical options. Alternative pain management regimens with the introduction of botulinum toxin as well as tricyclic medication have reduced the need for any invasive management. The surgical management of the TMJ has been revolutionised by the introduction of arthroscopy in the late 1970s. The use of arthroscopy and arthrocentesis has lead to a reduction in indications for open joint surgery. There is no longer a perceived need to correct internal derangement with disc repositioning surgery. The primary management of acute restriction of opening and joint pain is now with arthrocentesis and arthroscopy. Degenerative and ankylotic conditions of the joint can be safely treated by the use of alloplastic joint replacement, which has less morbidity and more predictable outcomes than costochondral grafting, with the latter still the method of choice in children. The revolution continues with the introduction of national guidelines and databases supported by BAOMS.

We describe an unusual case of a 31-year-old man who presented with generalised pain in his jaw after referral by his general dental practitioner. Langerhans histiocytosis was diagnosed and treatment started with azathioprine.

Unlabelled: This study aimed to investigate whether granisetron reduces masseter muscle pain and allodynia induced by hypertonic saline. Fifteen healthy women and 15 age-matched healthy men participated in this randomized, placebo-controlled, double-blinded study. They first received bilateral injections of hypertonic saline into the masseter muscles (internal control). The evoked pain intensity and the pressure-pain threshold (PPT) were recorded during 30 minutes. Granisetron was then injected on one side and placebo (normal saline) on the contralateral side. Two minutes thereafter, the hypertonic saline injections were repeated. Pain and PPT were again recorded. The first injection of hypertonic saline induced pain of similar intensity, duration, and pain area on both sides, but with larger pain area in the women (P = .017). The PPT did not change significantly. The second injection of hypertonic saline induced considerably less pain (62.5%), of shorter duration (44.1%), and of smaller area (77.4%) on the side pretreated with granisetron (P = .005). The PPT was increased on the granisetron side in the men (P = .002). The results of this study show that local injection of a single dose of granisetron attenuates masseter muscle pain induced by hypertonic saline., Perspective: This article presents the changes of hypertonic saline-induced masseter muscle pain characteristics by infusion of granisetron. It appears that the pain-inducing effect in this experimental pain model is partly due to activation of 5-HT3-receptors. Hence, the results indicate that granisetron might offer a new treatment approach for localized myofascial pain.

Peripheral action of opioids for pain control, for which local inflammation has been shown to be crucial, is being increasingly used in clinical practice. The aim of this study was to evaluate the hypothesis that addition of fentanyl to lidocaine, when injected into inflamed dentoalveolar tissues, can improve the quality of analgesia during surgery. Seventy-one patients reporting with pain and tenderness in the maxillary tooth were assigned into the experimental (LAF) or control (LA) group in a prospective, randomized double-blind trial. The LAF group (n = 36) was injected submucosally with a mixture of 40 microg of fentanyl (0.8 ml) and 2% lidocaine hydrochloride with 1:200000 adrenaline (2 ml). In the LA group (n = 35) 0.9% of saline (0.8 ml) was added instead of fentanyl. The pain scores were recorded before injecting, 5 min after injection, and immediately after surgery using a visual analogue scale. The mean pain scores were not significantly different at all time intervals. Twelve patients in the LAF group (2.75+/-0.72 ml) and ten patients in the LA (2.90+/-0.70 ml) group required additional local anaesthetic to achieve pain control. In conclusion, there was no improvement in quality of intraoperative analgesia on addition of fentanyl to lidocaine in inflamed dentoalveolar tissues.

Unlabelled: The aim of the current study was to adapt the orofacial formalin pain model previously developed in rats for use in mice and to characterize as fully as possible the behavioral changes in this species. The effects of subcutaneous injection of different formalin concentrations (.5%, 1%, 2%, 4%, and 8%) were examined on the face-rubbing response. In mice, formalin injection into the upper lip induced sustained face-rubbing episodes with vigorous face-wash strokes directed to the perinasal area. A positive linear relationship between formalin concentration and amplitude of the rubbing activity was observed during the first and second phase of the test with concentration up to 4%. With the highest concentration used (8%), the amplitude of both phases had plateaued. Systemic administration of morphine and paracetamol induced a dose-dependent inhibition of the rubbing behavior during the second phase. Although both paracetamol and morphine inhibited the first phase, a dose-dependent inhibition was found only for morphine. The ED50 value (95% confidence interval) for suppressing the rubbing response during the first phase was 2.45 mg/kg (1.90-3.08 mg/kg) for morphine. The ED50 values for suppressing the rubbing response during the second phase were 3.52 mg/kg (2.85-4.63 mg/kg) for morphine and 100.66 mg/kg (77.98-139.05 mg/kg) for paracetamol. Heterosegmental nociceptive stimulation evoked by subcutaneous injection of capsaicin into the back of the animal 10 min before the formalin test produced a dose-dependent inhibition of the second phase of the rubbing response. The ED50 values for suppressing the rubbing response during the first and second phases were 9.04 microg (1.36-65.13 microg) and 0.92 microg (0.28-2.99 microg), respectively. In conclusion, the mouse orofacial formalin test appears to be a reliable model for studying the behavioral encoding of the intensity of nociceptive orofacial stimulation and the counter-irritation phenomenon and for testing analgesic drugs., Perspective: To further exploit the new opportunities of investigating nociceptive processing at the molecular level with the transgenic "knockout" approach, we require suitable behavioral models in mice. The presented mouse orofacial formalin test appears to be a reliable model for studying the behavioral encoding of the intensity of nociceptive stimulation and the counter-irritation phenomenon and for testing analgesic drugs.

Unlabelled: The aim of this study was to further validate our carrageenan-induced temporomandibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local beta-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of beta(2)but not the blockade of the beta(1)-adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. In the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of beta(2)-adrenoceptors., Perspective: The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating beta(2)-adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs.

Melorheostosis is a linear bone dysplasia of unknown origin that may be associated with soft-tissue alterations. Although any part of the skeleton can be affected, this condition is rarely observed in the craniofacial region. Only seven cases of melorheostosis with craniofacial involvement have been reported and cranial manifestation only is even rarer. To the authors' knowledge, manifestation in the mandible only has not yet been documented. A patient with isolated melorheostosis of the mandible with characteristic symptomatic bone pain is presented. The clinical, radiological and histological findings are described and possible therapeutic options are discussed.

We report a case of diffuse sclerosing osteomyelitis of the mandible responded to alendronate, after a poor response to intravenous antibiotics, antibiotic irrigation-perfusion, and decortication. The patient was given an intravenous infusion of 10mg of alendronate. Pain resolved within 24 h. There were no severe adverse events. Increased uptake of 99mTc in the mandible almost completely disappeared 3 months after treatment.

Analyzing feeding behavior, and in particular meal duration, can be used as a biological marker for temporomandibular joint (TMJ) inflammation/pain. The present study determined the specificity of meal duration as a measure of TMJ inflammation/pain in a rodent model. The model was also used to test the efficacy of dexamethasone (DEX) as a treatment for TMJ inflammation/pain that was induced by TMJ injection of complete Freund's adjuvant (CFA). In the first study, anesthetized male Sprague-Dawley rats housed in computerized feeding modules received bilateral intra-articular knee injections of CFA or saline. The next day, CFA-injected rats had significant knee swelling and impaired mobility. Food intake in the CFA-injected group was reduced over the next two days and this was due to reduced meal number with no change in meal size. Notably, meal duration was normal in both the CFA and saline knee-injected groups. In the second study, male rats were assigned to one of four groups: Group 1, no CFA and no DEX treatment; Group 2, no CFA and treatment with DEX (0.4 mg/kg i.m. once daily); Group 3, bilateral TMJ CFA injection and no DEX treatment; and Group 4, bilateral TMJ CFA injection and treatment with DEX. CFA significantly increased TMJ swelling and stress-induced chromodacryorrhea in Group 3, but treatment with DEX attenuated these effects in Group 4. Compared to the controls, meal duration was significantly lengthened 24 and 48 h post-CFA injection in Group 3, whereas DEX treatment attenuated TMJ swelling, chromodacryorrhea and normalized meal duration. The data demonstrate that meal pattern analysis, and in particular meal duration, can be used as a non-invasive specific measure of TMJ inflammation/pain and can be used as a marker of DEX treatment efficacy.

Defining the aetiology of facial pain can be difficult. While acknowledging the principle of 'common things are common', it is prudent to consider all possible causes. We describe a patient with posterior scleritis that presented as facial pain and was cured by oral prednisolone., (Copyright 2003 The British Association of Oral and Maxillofacial Surgeons)

In a randomised, double-blind placebo-controlled single-centre study we compared the efficacy and safety of 0.75% levobupivacaine (without vasoconstrictor) with 2% lignocaine (with adrenaline 1:80,000) and with placebo for postoperative pain relief in 93 patients having day surgery under general anaesthesia for the removal of impacted mandibular third molars. Premedication and preoperative analgesics were not prescribed, although a short-acting opioid analgesic agent was allowed if required during the anaesthetic procedure. Patients were asked to keep a diary card for 2 days after discharge from hospital. The primary endpoint was the number of patients who requested analgesia within 2 h of completion of the operation. In total, 16 (53%) of patients given levobupivacaine requested analgesia compared with 22 (71%) given lignocaine and 23 (72%) given placebo. Patients given levobupivacaine had lower maximum visual analogue pain scores (VAS) and took longer to request rescue medication (P=0.045 compared with lignocaine). Fewer patients after levobupivacaine n=20 (7%) than after lignocaine n=7 (23%) or placebo n=5 (16%) experienced adverse events. Levobupivacaine seems to be a suitable alternative local anaesthetic to lignocaine with adrenaline for pain control after oral operations.

This study analyzes the combination of oral ketorolac 10 mg with varying amounts of codeine phosphate, and the postoperative pain relief that developed from these combinations. Five groups of patients were administered the codeine/ketorolac combinations. Variations of the combinations were analyzed to ascertain if an optimal analgesic ratio existed. All controllable variables involved with the surgical procedure were held constant to allow for better evaluation of postoperative pain. Results obtained from 67 patients indicated that the best pain relief was achieved with a combination of 10 mg ketorolac and 15 mg codeine phosphate. Codeine alone provided adequate analgesia, but the addition of ketorolac reduced the patients' perceived side effects. The presence of codeine in the analgesic combination was also shown to reduce the number of days that the patient required the medication postoperatively. Reducing the duration of medication use postoperatively may also minimize the possible side effects of ketorolac and codeine, which could develop with extended periods of use.

Diffuse sclerosing osteomyelitis (DSO) of the mandible is a chronic condition, the cause of which is not known. Jaw pain, occurring irregularly, is a typical symptom. The aim of the study was to assess the effectiveness of disodium clodronate for relieving pain in patients with DSO. Disodium clodronate is a bisphosphonate used to treat diseases of bone and calcium metabolism. Ten DSO patients experiencing pain received disodium clodronate or placebo intravenously on a randomized double-blind basis. Both minimum (300 mg) and maximum (900 mg) doses were well tolerated. Disodium clodronate administration did not result in better immediate pain relief than placebo administration. However, 6 months after treatment there was a statistically significant difference in pain intensity between the groups, with the disodium clodronate group experiencing significantly less pain.

The object of the study was to assess the comparative efficacy of three single doses (200, 400, 600 mg) of soluble ibuprofen and ibuprofen tablets after third molar surgery in 148 patients and aged 18-40 years. Outcome was measured by overall assessment of pain (AUC360) assessed from serial visual analogue scales, the number of patients taking additional analgesic and by overall assessment of medication evaluated on a five-point categorical scale. Over the 6-hour investigation period all the ibuprofen treatments with the exception of ibuprofen tablets 200 mg resulted in significantly less pain (p < 0.05) than placebo treatment. A large number of patients required additional analgesia during the investigation period, but the time to taking it was significantly earlier in the placebo group. No significant dose response (p > 0.05) was observed for either ibuprofen preparations assessed by the outcome variable of overall pain experience (AUC360) or time to additional analgesia. There was no significant difference in pain scores or time to taking additional analgesics between the respective doses of soluble and tablet formulations of ibuprofen. Both soluble and tablet formulations of ibuprofen provide effective pain control in the early postoperative period after removal of impacted third molars. There is little analgesic advantage in increasing the dose to 600 mg and only minimal benefit from using a soluble formulation of the drug.

The aim of this preliminary study was to investigate and assess the effect of intra-articular injection of superoxide dismutase (SOD) in patients with temporomandibular joint (TMJ) dysfunction who had not responded to conservative therapy in a first study. Thirty joints in 29 patients were studied. The results showed that intra-articular injection of superoxide dismutase was effective in 25 joints (83%). It was concluded that intra-articular injection of superoxide dismutase may be an alternative therapy for patients with TMJ dysfunction who fail to respond to conservative treatment.

A retrospective study of 64 patients with orofacial dysaesthesia is presented. Special emphasis is placed on the patients' symptoms and on the manipulative treatments they received before they were referred for psychiatric consultation. The patients had suffered from chronic orofacial pain or feelings of discomfort for periods ranging from 6 months up to 25 years. The patients had visited several specialists and had received numerous manipulative or medical treatments, the most common of which were repeated medication (drug treatment), TMJ dysfunction treatment, endodontic or exodontic treatment, and surgical explorations. However, the success of all these clinical efforts was very limited because of the apparent psychosomatic origin of the complaints. This study clearly shows that psychiatric consultations are still too seldom made in patients with chronic orofacial dysaesthesia, that many patients have a mental disorder, and that most chronic psychosomatic pain disorders are treated as acute specific pain.

8 cases of vasogenic facial pain are presented with delineation of differentiating clinical features. These vasogenic syndromes include classic episodic cluster headache, chronic cluster headache, and indomethacin responsive chronic cluster headache. Open clinical trials employing inhalation O2 therapy as an abortive treatment strategy utilized in combination with prophylactic nifedipine therapy proved highly efficacious in controlling pain among most classic and chronic cluster headaches. A single case of chronic paroxysmal hemicrania responded favorably to indomethacin.