Journal of Oral & Facial Pain and Headache, 01/2015

Aims: To carry out a systematic review to assess the effectiveness of cannabis extracts and cannabinoids in the management of chronic nonmalignant neuropathic pain. Methods: Electronic database searches were performed using Medline, PubMed, Embase, all evidence-based medicine reviews, and Web of Science, through communication with the Canadian Consortium for the Investigation of Cannabinoids (CCIC), and by searching printed indices from 1950. Terms used were marijuana, marihuana, cannabis, cannabinoids, nabilone, delta- 9-tetrahydrocannabinol, cannabidiol, ajulemic acid, dronabinol, pain, chronic, disease, and neuropathic. Randomized placebo-controlled trials (RCTs) involving cannabis and cannabinoids for the treatment of chronic nonmalignant pain were selected. Outcomes considered were reduction in pain intensity and adverse events. Results: Of the 24 studies that examined chronic neuropathic pain, 11 studies were excluded. The 13 included studies were rated using the Jadad Scale to measure bias in pain research. Evaluation of these studies suggested that cannabinoids may provide effective analgesia in chronic neuropathic pain conditions that are refractory to other treatments. Conclusion: Cannabisbased medicinal extracts used in different populations of chronic nonmalignant neuropathic pain patients may provide effective analgesia in conditions that are refractory to other treatments. Further high-quality studies are needed to assess the impact of the duration of the treatment as well as the best form of drug delivery. Keywords: cannabinoids, chronic nonmalignant pain, management, neuropathic pain, systematic review

Aims: To evaluate the impact of cigarette smoking on the sleep quality of patients with masticatory myofascial pain and to determine whether the association between smoking and impaired sleep is influenced by other factors such as demographic, psychological, and behavioral variables. Methods: Data from a retrospective case series of 529 patients diagnosed with masticatory myofascial pain according to group I of the Research Diagnostic Criteria for Temporomandibular Disorders were obtained. Patients completed a standardized pain questionnaire and psychometric tests. Differences between smokers and nonsmokers were evaluated using independent samples t tests and chi-square tests. Hierarchical linear multiple regression models were used to examine predictors of sleep disturbances. Results: Of the entire sample, 170 (32%) reported that they were smokers. Smokers reported higher pain severity and more sleep disturbances and psychological distress than nonsmokers. Cigarette smoking significantly predicted sleep disturbance (β = 0.229, P .001), but this relationship was attenuated after controlling for pain severity and psychological distress (β = 0.122, P .001). Conclusion: Cigarette smoking is associated with numerous adverse health outcomes, including pain severity, alterations in mood, and disrupted sleep, and seems to be a significant predictor of sleep quality in patients with masticatory myofascial pain. Keywords: masticatory myofascial pain, psychological distress, sleep quality, smoking, temporomandibular disorders

Aims: To investigate the prevalence of sleep disturbance and psychologic distress in a population of Chinese patients with temporomandibular disorders (TMD) and whether sleep disturbance and psychologic distress are risk indicators for TMD. Methods: Validated Chinese versions of the Self-Rating Scale of Sleep (SRSS) and Depression, Anxiety and Stress Scales-21 (DASS-21) were used to measure sleep disturbance and psychologic distress of 510 TMD patients with a mean (± SD) age of 31.06 ± 14.40 years. TMD signs/symptoms and sociodemographic data were also collected. The patients were divided into seven diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). For statistical analysis, the patients were subsequently grouped into those with (n = 128) and without (n = 382) myofascial pain. The data were analyzed using chi-square tests, independent-samples t test, as well as stepwise logistic regression at a significance level of P .05. Results: The prevalence of moderate to severe sleep disturbance and psychologic distress was significantly higher in the myofascial pain group than in the non-myofascial pain group (P .05). Stepwise logistic regression analysis demonstrated that sleep disturbance and anxiety were possible risk indicators for myofascial pain, with odds ratios of 2.41 and 4.10, respectively (P .05). Conclusion: The Chinese population of TMD patients frequently reported a disturbed sleep condition and psychologic distress symptoms. Sleep disturbance and psychologic distress symptoms are possible risk indicators for myofascial pain in this population. Keywords: myofascial pain, psychologic distress, risk indicator, sleep disturbance, temporomandibular disorders

Aims: To test the hypothesis that experimental pain in the masseter muscle or temporomandibular joint (TMJ) will decrease the anterior maximum voluntary bite force (MVBF) and jaw muscle activity in relation to the perceived effort. Methods: Sixteen volunteers participated in two experimental sessions. Participants were injected with 0.2 mL of monosodium glutamate (1.0 M) into either the masseter muscle or TMJ. The MVBF and corresponding electromyographic (EMG) activity of the masseter, anterior temporalis, and digastric muscles were recorded 10 times at an interval of 2 minutes before and after injection. Pain was measured using a visual analog scale and McGill Pain Questionnaire. In addition, participants were asked how they perceived the interference of pain on their biting performance. The data analysis included a two-way analysis of variance model and t test. Results: There was no significant difference in peak pain intensity (P = .066) and duration of pain (P = .608) between painful muscle and TMJ injections, but TMJ injection produced a significantly larger area under the curve (P = .005) and a significantly higher pain rating index (P = .030). Pain in the muscle (P = .421) and TMJ (P = .057) did not significantly change the MVBF from baseline levels. The EMG activity also did not differ significantly from baseline levels during muscle pain. However, there was a significant increase (P = .028) in the EMG activity of the anterior temporalis and a significant decrease (P = .010) in the EMG activity of the anterior digastric muscle compared to baseline during TMJ pain. Subject-based reports also revealed that in the majority of cases (62.5%), pain did not interfere with the MVBF task. Conclusion: Experimental pain from either masseter muscle or TMJ did not affect the MVBF, in accordance with the subject-based reports. Jaw muscle activity, except for EMG activity of the anterior temporalis and anterior digastric muscles during TMJ pain, also remained unaffected by pain. The findings suggest that it is not pain in itself but rather how pain is perceived that may lead to adaptation of motor function, supporting an integrated pain adaptation model. Keywords: electromyography, integrated pain adaptation model, monosodium glutamate

Aims: To compare the effects of occlusal appliance therapy (OA) and therapistguided relaxation training (RT) on temporomandibular disorder (TMD) pain in adolescents, thereby replicating a previous randomized controlled trial, and to explore whether additional therapy administered in a crossover sequential design improves treatment outcomes. Methods: The study involved 64 adolescents, aged 12 to 19 years, experiencing TMD pain at least once a week and diagnosed with myofascial pain in accordance with the Research Diagnostic Criteria for TMD. For phase 1 of the study, subjects were randomly assigned to OA or RT; nonresponders were offered the other treatment in phase 2. Self-reports of TMD pain and clinical assessments were performed before and after treatment in each phase and 6 months after the last treatment phase. Differences in outcomes between treatment groups across the different phases were analyzed by analysis of covariance (ANCOVA), and for differences in proportions, the chi-square test was used. Results: After phase 1, a significantly higher proportion of adolescents treated with OA (62.1%) than those treated with RT (17.9%) responded to treatment, defined as a subjective report of "Completely well/Very much improved" or "Much improved." Similar differences in self- report of treatment effect occurred after phase 2. About two-thirds of all adolescents in both phases reported such an improvement level at the 6-month follow-up, including a somewhat higher proportion of phase 1 responders (79.2%) than phase 1 nonresponders (60%). Conclusion: The findings suggest that, for adolescents with TMD pain, use of standardized clinical treatment with OA is more effective than RT on selfevaluation of treatment improvement. For nonresponders, subsequent crossover treatment might be useful to improve subjective TMD pain. Keywords: adolescence, occlusal appliance, randomized controlled trial, relaxation training, temporomandibular disorders

Aims: (1) To determine the prevalence of temporomandibular disorder (TMD)-pain complaints in the general Dutch population; (2) to investigate its relationship with age, sex, educational attainment, and country of birth; (3) to determine its association with other pain complaints; and (4) to determine whether there are TMD subgroups (ie, with regard to their sociodemographic variables) that are more vulnerable for comorbid pain complaints. Methods: Data from two large-scale population studies were available: 975 randomly selected adults, who were interviewed by an examiner from the Institute for Applied Scientific Research (TNO), and 11,948 adults who were registered in the Netherlands Twin Register and responded to a survey questionnaire. Chisquared tests and regression analyses were used to determine whether there were any associations between the presence of TMD pain and the various sociodemographic or comorbid variables. Results: The prevalence of TMDpain complaints was 7.2% to 8.0%, and around twice as high in women than in men. The results were inconclusive for association with age, and no evidence was found for an association with country of birth or educational attainment. TMD-pain complaints were strongly related to the presence of other pain complaints. Interestingly, the number of reported comorbid complaints was related to all of the studied sociodemographic variables. Conclusion: In the general Dutch population, women more often report TMD-pain complaints than men, and patients with TMD-pain complaints more often show other pain complaints than persons without TMD pain. In contrast to common beliefs, no clear association with age was found. Furthermore, widespread pain complaints were more common in non-native Dutch and lower-educated females. Keywords: pain comorbidity, prevalence, sociodemographic variables, temporomandibular-pain complaints

Aim: To test whether orofacial mechanical and thermal hypersensitivities occur in rats during orthodontic tooth movement (OTM). Methods: Sprague-Dawley rats (140 to 160 g) were divided into an experimental (E) group (n =7), with an active orthodontic spring placed in the right side of their mouth, and a sham (S) group (n = 7), with an inactive orthodontic spring. Mechanical sensitivity was tested preoperatively (1 day before attaching the orthodontic spring) and postoperatively (1 hour, 3 hours, 6 hours, days 1 to 7, day 14, day 21, and day 28 after orthodontic spring attachment) on the cheek, upper lip, and maxillary incisor labial gingiva bilaterally by recording the threshold for a head withdrawal response evoked by von Frey filaments. Thermal sensitivity was also tested preoperatively and postoperatively on the cheek bilaterally by applying a noxious thermal stimulus and measuring head withdrawal response duration, response score, and response percentile rate. Statistical analyses involved a mixed-model repeated-measures analysis of variance (MMRM ANOVA). Results: The mechanical and thermal sensitivities at all bilateral sites were significantly increased (P .01) in the E group in the early postoperative period (1 to 5 days), with peaks reached on day 1, and then returned to and remained at preoperative levels until postoperative day 28. However, there was no significant change from the preoperative levels in mechanical and thermal sensitivities for the S group for all the tested sites. Conclusion: This rat OTM-induced pain model correlates with the time course of OTM-induced pain in humans and suggests that OTM-induced mechanical and thermal hypersensitivities may be useful measures of OTM-induced pain. Keywords: behavioral changes, malocclusion, orofacial, orthodontic appliances, sensitization

Aims: To explore the possible relationship between protein kinase C gamma (PKCγ) and phosphorylated forms of extracellular signal-regulated kinases 1/2 (pERK1/2) in the rat medullary dorsal horn and the facial hypersensitivity indicative of dynamic mechanical allodynia (DMA) following chronic constriction of the infraorbital nerve (CCI-IoN). Methods: A well-established rat model of trigeminal neuropathic pain involving CCI-IoN was used. Facial mechanical hypersensitivity was tested with non-noxious dynamic mechanical stimulation (air-puff), and the medullary dorsal horn was examined immunohistochemically using PKCγ and pERK1/2 as pain markers. Statistical analysis was performed using Student t test or one-way analysis of variance (ANOVA). Results: Increased PKCγ and pERK1/2 expressions within the medullary dorsal horn were associated with DMA following CCI-IoN. A segmental network composed of PKCγ-positive cells located in medullary dorsal horn laminae II/III, contacting more superficially located pERK1/2-expressing cells, was identified. Ultrastructural analysis confirmed the presence of PKCγ to pERK1/2-positive cells. Moreover, intracisternal administration of the selective PKCγ inhibitor KIG31-I blocked both the DMA and pERK1/2 expression in a dose-dependent manner. Although the number of pERK1/2-positive cells was significantly elevated with air-puff stimulation, DMA rats not receiving air-puff stimulation showed significant pERK1/2 expression, suggesting they were experiencing spontaneous pain. Conclusion: PKCγ cells in the medullary dorsal horn may be involved in DMA following CCI-IoN through the activation of pERK1/2-expressing cells, which then may relay nonnociceptive information to lamina I cells in the medullary dorsal horn. Keywords: chronic constriction of infraorbital nerve, dynamic mechanical allodynia, neuropathic pain, protein kinase C gamma

Aims: To use simple thermal devices with different diameters and temperatures to investigate reliability and magnitude of human intraoral thermal sensitivity. Methods: Sixteen healthy volunteers participated. Six thermal devices with tapered circular ends (stimulus diameter 3, 5, and 10 mm) were used. Three different temperatures (room temperature, heat, and cold) were applied with each of the three diameters, ie, nine combinations. Participants were stimulated in randomized order at nine different sites: tongue, lip, maxillary attached gingiva adjacent to the left and right central incisors (without touching the lip) and to the left and right premolars (with or without touching the lip), and the left and right cheeks extraorally. Participants rated the perceived stimulus intensity on 0-50- 100 numeric rating scales (NRS). The number of paradoxical thermal sensations was also recorded. Ten volunteers were examined twice on the same day and recalled for a second session for assessment with the 5-mm-diameter device of within- and between-session reliability (interclass correlation coefficients [ICC]). The results were analyzed using a three-way analysis of variance. Results: Reliability of NRS scores ranged from poor (ICC = 0.09, with cold stimulation at the premolar region) to excellent (ICC > 0.92, with cold stimulation at the cheek or tongue). NRS values varied with stimulus diameter (P .050), temperature (P .001), and sites (P .001), with significant size × site and temperature × site interactions (P .001). The tongue was the most sensitive site (P .001) and the gingiva was the least sensitive site (P .050). The 10-mm-diameter device produced higher NRS scores than the 3-mm-diameter device. Conclusion: The reliability of intraoral thermal sensitivity recorded with the 5-mm-diameter device varied greatly between different sites. Nonetheless, with this caveat in mind, the study did document that semiquantitative assessment of intraoral thermal sensitivity is feasible and applicable for clinical studies in different intraoral pain conditions. Keywords: intraoral, quantitative sensory testing, somatosensory sensitivity, thermal

This article reports a case of masticatory muscle pain and progressive limited mouth opening secondary to amyotrophic lateral sclerosis (ALS), popularly known as Lou Gehrig's disease. The symptoms were first mistaken as those of temporomandibular disorders, before fatty degeneration of all masticatory muscles were discovered on magnetic resonance imaging (MRI). ALS should be considered in the differential diagnosis process when the patient presents with longstanding progressive mouth opening limitation associated with pain. MRI could facilitate the diagnostic process. Keywords: amyotrophic lateral sclerosis, motor neuron disease, mouth opening limitation, orofacial pain