Journal of Oral & Facial Pain and Headache, 01/2005

This article presents an overview of possible mechanisms associated with pain perception, with a specific focus on understanding unusual manifestations of orofacial pain associated with nerve insult. It includes recent evidence concerning neurobiological changes that occur in the periphery at tissue and nerve sites, or within the central nervous system, and that may involve chemical and inflammatory responses, sensitization, or alterations of cellular function. Moreover, the contribution of the autonomic nervous system, changes in emotional reactivity and vigilance, the roles of high brain centers such as the basal ganglia (nigro-striatal) system, and the influence of aging and gender, are briefly described. Keywords: chronic pain, nerve damage, orofacial pain, pain, pain perception, nervous system

Aims: To determine the ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve during the surgical removal of lower third molar teeth and to establish whether any characteristics were different between patients with dysesthesia and patients without dysesthesia. Methods: Transmission electron microscopy was used to determine the ultrastructural morphological characteristics of human lingual nerve neuromas (n = 34) removed at the time of microsurgical nerve repair. From a sample population of myelinated and nonmyelinated fibers within the neuromas, fiber diameter, myelin thickness, g-ratio, and the number of mitochondria per axon were quantified. Comparisons were made with normal control lingual nerve specimens (n = 8) removed at the time of organ donor retrieval. Results: Significant differences in ultrastructural morphology were found between the neuromas and control nerves. The neuromas contained a higher proportion of small (2- to 8-µm diameter) myelinated nerve fibers than controls, and the mean myelinated fiber diameter was significantly lower in neuromas than in controls. Mean myelin sheath thickness was significantly thinner in neuromas (0.6 ± 0.1 µm) than in controls. However, the g-ratio, which is a measure of the myelination status of the nerve fibers in relation to their diameter, was found to be similar in each group, suggesting a normal process of myelination in the damaged axons. Nonmyelinated axon diameter was also significantly smaller in the neuromas than in the controls, and Schwann cells were found to sheathe more nonmyelinated axons in neuromas than in controls. The ratio of nonmyelinated to myelinated axons was significantly higher in neuromas than in controls. However, no significant differences were found between patients with dysesthesia and those without dysesthesia. Conclusion: Damage to the lingual nerve results in marked changes to axon diameter, myelin sheath thickness, and Schwann cell-axon relationships. These ultrastructural changes could contribute to the altered electrophysiological properties of axons trapped within neuromas. However, no significant differences in the ultrastructural characteristics studied were found between specimens from patients with or without symptoms of dysesthesia. Keywords: dysesthesia, human lingual nerve, traumatic neuromas

Aims: To determine temporal changes in the concentrations found in the temporomandibular joint (TMJ) and trigeminal ganglion of 3 specific classes of inflammatory mediators commonly linked with conditions of joint inflammation. The intent was to determine whether concentrations of the neuropeptide calcitonin gene-related peptide (CGRP), the neurotrophin nerve growth factor (NGF), and the proinflammatory cytokines interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) are altered in the trigeminal ganglion and TMJ tissues during various stages of adjuvant-induced inflammation of the rat TMJ. Methods: Adult male rats received bilateral TMJ injection of complete Freund's adjuvant (CFA), while control rats did not receive CFA treatment. The trigeminal ganglion and TMJ tissues were collected at 2 days, and 2, 4, and 6 weeks postinjection and analyzed using either radioimmunoassay or enzyme-linked immunosorbent assay. Results: In the trigeminal ganglion, both CGRP and NGF concentrations were significantly elevated in comparison to controls from 2 days to 4 weeks; however, the patterns of increase differed. Concentrations of each inflammatory mediator were significantly elevated in the TMJ tissues of CFA-injected animals at 2 days and continued to be significantly elevated throughout the 6-week period. CGRP content remained at peak levels from 2 days through 6 weeks, while peak content for NGF, IL-1b, and TNF-a was found at 2 days through 2 weeks. Conclusion: The results suggest that the development of CFA-induced inflammation of the TMJ was accompanied by a variable increase in the concentration of different classes of inflammatory mediators in both the trigeminal ganglion and TMJ tissues, which implies that each class of inflammatory mediator may play a significant role during different stages in the onset and exacerbation of the inflammatory process. Keywords: calcitonin gene-related peptide, inflammation, interleukin- 1ß, nerve growth factor, temporomandibular joint, trigeminal ganglion, tumor necrosis factor-α

Aims: To investigate the presence of endogenous b-endorphin, an opioid, in the synovial lavage fluid of the temporomandibular joint (TMJ), and to compare the concentration of ß-endorphin in patients with closed lock with that in symptom-free subjects. Methods: Thirty-eight patients (38 joints) with closed lock diagnosed on the basis of the results of clinical examination and magnetic resonance imaging (MRI) and 11 healthy volunteers (19 joints) were examined. Samples of lavage fluid were obtained prior to arthrocentesis by washing the joint with saline. Samples were assayed for b-endorphin by an enzyme immunoassay, and concentrations of protein were measured by a bicinchoninic acid assay. Subjective pain was assessed by patients using a visual analog scale. Bone changes in the condyle were assessed by MRI, and synovitis was assessed on the basis of arthroscopic findings. Results: ß-endorphin was present in the synovial fluid of the TMJ, and the concentration was significantly higher in patients with closed lock of the TMJ compared to symptom-free volunteers. The b-endorphin levels were not, however, significantly correlated with clinical parameters in the patients. Conclusion: The study results support recent findings that some opioids and their receptors exist not only within the central nervous system but also in the TMJ region, and that opioid concentrations are higher in patients with pain and dysfunction of the TMJ. Keywords: arthrocentesis, ß-endorphin, synovial fluid, temporomandibular joint

Aims: To study the relationship between generalized joint hypermobility (GJH) and temporomandibular disorders (TMD) by assessing prevalence and patient characteristics of TMD in a population of patients with maximum expression of GJH as a symptom of inherited connective tissue disease. In addition, diagnostic reliability of a series of clinical signs indicative of temporomandibular joint (TMJ) hypermobility was tested. Methods: The study sample consisted of 42 subjects with GJH, 24 with Marfan syndrome and 18 with Ehlers-Danlos syndrome. A subgroup of 27 individuals was selected by age (>= 18 yrs) and was compared to 40 controls with TMD and normal peripheral joint mobility. TMD diagnoses were assigned to each subject according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Results: In the GJH sample (n = 42), 71.4% of the subjects were symptomatic for TMD. Of those, 13.3% had sought treatment. A myofascial pain diagnosis was made in 69%, disc dislocation with reduction was diagnosed in 85.7%, and TMJ arthralgia in 61.9%. Multiple TMD diagnoses were assigned in 69% of the subjects; of these, 57% had 3 or more subgroup diagnoses. Joint noises (P < .01) and recurrent TMJ dislocations (P < .01) were a frequent finding in adult GJH subjects (n = 27) compared to controls, with symptomatic GJH subjects presenting more and more prolonged dislocation events than asymptomatic subjects (P < .001). TMJ hypermobility signs were expressed significantly more often in GJH compared to controls with TMD and normal joint mobility. Conclusion: This study indicates a positive relationship between GJH and TMD. Keywords: joint hypermobility, temporomandibular disorders, temporomandibular joint, temporomandibular joint dislocation

Aims: To determine whether there is a difference in terms of reliability between experienced examiners and inexperienced examiners in the measurement of signs of temporomandibular disorders (TMD). Methods: A total of 27 patients seen for treatment of TMD were rated blindly and in random sequence by 2 experienced and 2 inexperienced examiners. The examiners participated in a 4-hour calibration session on the day preceding the reliability study. Both experienced and inexperienced examiners participated in the calibration session to reduce the effect of examiner subjectivity and allow the study focus to be on the effect of experience. The rating followed the Research Diagnostic Criteria for Temporomandibular Disorders and included mandibular movements, joint sounds, and digital palpation of muscles and joints. Intraclass correlation coefficients and kappa statistics were calculated to estimate interrater reliability. The Wilcoxon signed rank test was performed to test for differences between experienced and inexperienced examiners' results, and the Friedman test was used for differences between all 6 examiner combinations. Results: Excellent overall reliability was found for vertical mandibular motions, acceptable reliability was found for the summed muscle palpation pain sites, and moderate to poor reliability was found for excursive movements, joint sounds, and single muscle palpation pain sites. No significant differences in the measurement results could be found between the experienced examiners and the inexperienced examiners. Conclusion: Examiner calibration rather than professional experience seems to be the most important factor for reliable measurement of TMD symptoms. Keywords: calibration, reliability, temporomandibular disorders

An earlier version of this report was presented at the annual meeting of the International Association for Dental Research in San Diego, CA, in March 2002. Aims: To compare the clinical characteristics of diagnostic subtypes of temporomandibular disorders (TMD) based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) in terms of physical findings (Axis I) and psychosocial findings (Axis II) among Caucasian and African American young women. An ancillary goal was to assess the value of using self-reported TMD pain as a screening tool compared to RDC/TMD examinations. Methods: A biracial community sample (n = 830) of young women 19 to 23 years old was screened for facial pain with the Chronic Pain Grade questionnaire. Patients were considered to be putative cases of TMD if they reported facial pain present within the last 6 months; putative controls had no facial pain history or jaw symptoms. Women with facial pain more than 6 months ago and jaw symptoms (jaw symptom-past pain, JSPP group) were added. 129 women were clinically examined for TMD diagnosis for final confirmation of case-control status. Results: 41 of 43 Caucasian and 11 of 18 African American putative cases were confirmed as cases; 9 of 27 Caucasians, but 0 of 17 African Americans from the JSPP group were confirmed as cases. All 24 putative controls were confirmed as controls. Based on RDC/TMD Axis I, 80% of 61 cases were muscle-related diagnoses, 33% as disc-related diagnoses, and 48% as arthralgia/arthritis/arthrosis. Based on Axis I, there were no significant differences in diagnoses between African American and Caucasian women. Based on Axis II, cases had significantly greater depression (P = .002) and somatization with pain (P < .001) than controls as expected. African Americans had significantly greater somatization with pain than Caucasians (P = .020). There were no other significant racial differences. Conclusion: Among young women reporting facial pain, clinical TMD subtypes, pain impact, treatment utilization, and additional characteristics other than somatization with pain were similar between races. A high percentage of these young non-clinical cases presented severe depression and somatization. Keywords: African Americans, Caucasians, examinations and diagnoses, case-control studies, sensitivity and specificity

Aims: To investigate the effect of jaw clenching on the sensations evoked at segmental and nonsegmental levels by painful and nonpainful stimuli and in relation to hypnotic susceptibility. Methods: The effect of jaw clenching on painful and nonpainful sensations on the face and leg was studied in high-hypnotizable (HH) and low-hypnotizable (LH) subjects. Sixteen healthy subjects were selected and assigned to either the HH group (n = 8) or the LH group (n = 8). Painful and nonpainful electrical stimuli were delivered in random order to the face and leg. The subjects rated the intensity of the evoked sensation on a visual analog scale (VAS) while clenching or not clenching their jaw. Results: Jaw clenching significantly attenuated the VAS sensory ratings of all the subjects under various conditions (F1-31 = 6.15, P < .02). When the HH and LH subjects were analyzed separately, jaw clenching was found to be effective in reducing sensations only in the HH subjects (F1-15 = 8.30, P = .01), only those evoked in the face (segmental level), and only those evoked by nonpainful stimuli (tied Z = 2.52, tied P < .02). Conclusion: Sensory modulation produced by jaw clenching may be related to hypnotic susceptibility. On the whole, jaw clenching had a weak, local effect in modulating sensation, in contrast to its known widespread effect on motor behavior. Keywords: heterotopic stimulation, hypnotic susceptibility, jaw clenching, pain modulation, sensory modulation

Aims: Arthrogryposis multiplex congenita (AMC) is characterized by congenital contractures and joint deformities, but there are only a few reports of temporomandibular joint (TMJ) involvement. The objective of this investigation was to study the cause of limited mouth movement in this disease. Materials and Methods: Four individuals from a family affected by AMC over 5 generations were examined clinically and by magnetic resonance imaging (MRI) and 3-dimensional computerized tomography (3D-CT). Results: The CT scans of the 4 individuals showed hyperplasia of the coronoid process protruding into the infratemporal fossa in 2 of them and cranially to the zygomatic arch in the other 2; the hyperplasia was associated with mechanical limitation of the mouth opening. The MRI showed a disc displacement with reduction in 1 patient and a disc displacement without reduction in another; disc displacement could not be evaluated because of the limited mouth opening in the other 2. The condyle-disc complex of these last 2 individuals could only rotate. The MRI on T2- weighted images showed disc hyposignal in all cases but no alterations in the masticatory muscle tissue. The pedigree of the family suggests an autosomal dominant form of inheritance. Conclusions: The restriction of mouth opening in the 4 individuals affected by AMC was likely due to osseous dysplasia. Keywords: arthrogryposis, coronoid process, jaw locking, magnetic resonance imaging, mouth opening, 3-dimensional computed tomography