Increased ß-endorphin levels and generalized decreased pain thresholds in patients with limited jaw opening and movement-evoked pain from the temporomandibular joint.

PURPOSE: Patients with limited jaw opening and movement-evoked pain from the temporomandibular joint have moderate to severe pain that may be relieved by surgery. The purpose of this study was to investigate if the preoperative state is associated with alterations in plasma ß-endorphin (ßE) levels and pain thresholds. PATIENTS AND METHODS: Eighteen female patients with painful unilateral temporomandibular joint and 18 age-matched healthy women participated. After blood sampling for analysis of plasma ßE levels, pressure pain thresholds over the masseter muscles and index fingers were recorded with an electronic algometer. Electrical detection and pain thresholds were recorded with the PainMatcher (Cefar Medical AB, Lund, Sweden) device. Nonparametric statistics, ie, Mann-Whitney U test and Spearman correlation test, was used for statistical analyses. RESULTS: The patients showed higher plasma ßE levels (P = .013) and lower pressure pain thresholds over the masseter muscle at the painful side (P = .041) and bilaterally over the index fingers compared with the controls (P < .05 for all comparisons). High plasma ßE levels correlated to increased electrical detection thresholds (n = 36, r = 0.347, P = .038). CONCLUSIONS: This study showed that patients with limited jaw opening and movement-evoked pain from the temporomandibular joint had significantly higher plasma ßE levels and lower pressure pain thresholds in the orofacial area and at remote sites compared with pain-free, healthy, age-matched controls. An increased level of ßE seems insufficient to inhibit pain and central sensitization. Further studies are warranted to elucidate the relation between ßE and pain thresholds secondary to stress, inflammation, and discectomy.

Reduction in maximum pain after surgery in temporomandibular joint patients is associated with decreased beta-endorphin levels - a pilot study.

The mechanisms of relief from persistent pain after temporomandibular joint (TMJ) surgery are not well studied. It was hypothesized that if persistent pain is relieved by TMJ surgery, up-regulated parts of the central nervous system will be desensitized and the neuroendocrine opioid release will decrease back to normal levels. Eleven female patients with a mean age of 47.4±19.4 years and with TMJ pain due to chronic closed lock were examined before and 6-24 months after TMJ discectomy. The effects on plasma ß-endorphin levels, pain intensity, and pain thresholds were analyzed. Plasma ß-endorphin levels (P=0.032), pain at rest (P=0.003), and movement-evoked pain (P=0.008) were all significantly reduced at follow-up. The reduction in plasma ß-endorphin levels correlated with a reduction in maximum pain intensity (P=0.024) and with a longer time after surgery (P=0.041). Seven out of eight patients who reported a substantial reduction in maximum pain intensity presented a decrease in ß-endorphin levels in the plasma. In conclusion, this pilot study showed a significant reduction in plasma ß-endorphin levels and pain intensity at 6-24 months after TMJ surgery; plasma ß-endorphin levels were correlated with time after surgery. However, the results must be interpreted with caution since this was a single-centre observational study with a small sample size. If replicated in larger sample sets, the measurement of ß-endorphin levels may be of prognostic value for the treatment outcome.

Haemodynamic changes induced by submaximal isometric contraction in painful and non-painful human masseter using near-infra-red spectroscopy.

Although mechanisms underlying chronic muscle pain are poorly understood, one prevalent theory is that it is due, in part, to localized hypoxia. The purpose of this study was to evaluate this theory using non-invasive near-infra-red spectroscopy that monitors relative changes in intramuscular haemoglobin (Hb) concentration and oxygen saturation levels. Data were collected for the human masseter muscle during and following three isometric 30-s trials at 50% maximum voluntary contraction. Ten females, with a history of chronic muscle pain in the jaw, and eight matched healthy females without muscle pain (controls) participated. Results showed that, upon initiation of masseter muscle contraction, there was a rapid reduction in the intramuscular Hb concentration concomitant with a reduction in oxygen saturation levels. After cessation of the contraction, the Hb concentration increased rapidly and then fell toward the baseline. Significant differences in the recovery profile for oxygen saturation were found between the first trial and the following two trials for both the muscle pain- and control group. Looking at the first trial only, and adjusting for covariates of height, weight and bite-force in the analysis, revealed a marginally significant postcontraction difference between the two groups with a lower level of oxygen saturation during recovery in the group with chronic muscle pain. Significant group differences were found in Hb concentrations without any significant trial effect. It is likely that the well-known changes in intramuscular blood flow that occur during and after contraction in human muscles are reflected in these altered relative Hb concentrations. The group with chronic muscle pain showed a clearly reduced magnitude of the Hb concentration change in the postcontraction recovery period. The results support the concept that patients with chronic muscle pain have a slower intramuscular reperfusion during the recovery phase after sustained isometric contractions.

TMJ pain in relation to circulating neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis.

AIMS: The aim of this study was to test the hypothesis that temporomandibular joint (TMJ) pain is influenced by circulating levels of neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis. METHODS: Forty-three seropositive (RF+) or seronegative (RF-) rheumatoid arthritis patients and 24 healthy individuals were included in the study. RESULTS: High serum concentrations of serotonin were associated with low TMJ pressure pain thresholds and pain during mandibular movement in the RF+ patients. The results of this study do not support a relationship between circulating neuropeptide Y or interleukin-1 beta and TMJ pain. The RF+ patients had higher C-reactive protein levels and erythrocyte sedimentation rates than the RF- patients. There were also higher plasma levels of interleukin-1 beta in the RF+ patients than in the healthy individuals. Plasma levels of neuropeptide Y in the RF- patients were higher than in the healthy individuals. CONCLUSION: This study indicates that the serum concentration of serotonin is associated with TMJ allodynia in seropositive rheumatoid arthritis.

Thrombophilia, hypofibrinolysis, and alveolar osteonecrosis of the jaws.

OBJECTIVES: Our specific aim in 49 patients (42 women, 7 men) with osteonecrosis of the jaw was to determine whether thrombophilia (increased tendency to intravascular thrombosis) or hypofibrinolysis (reduced ability to lyse thrombi) were associated with this regional avascular necrosis. STUDY DESIGN: Determinants of thrombosis and fibrinolysis were compared in healthy controls and in 42 women and 7 men who had biopsy-proven idiopathic osteonecrosis of the jaw with severe chronic jaw or facial pain syndromes and failure to respond to conventional medical and dental treatments. RESULTS: Of the 49 patients, 35 (71%) had thrombophilia or hypofibrinolysis and only 14 were normal. Thrombophilia as a sole coagulation defect was found in 10 patients, 7 with resistance to activated protein C and 3 with low protein C (deficiency of an antithrombotic protein). Hypofibrinolysis with low stimulated tissue plasminogen activator activity and high lipoprotein (a) (an atherogenic, hypofibrinolytic lipoprotein) were found as sole coagulation defects in seven and eight patients, respectively. Ten patients had mixed defects; 7 of these 10 had thrombophilia with resistance to activated protein C. Sinusoidal dilatation was a constant feature in maxillary and mandibular bone biopsies, suggesting venous occlusion with intramedullary hypertension. Marrow fibrosis and occasional fibrin plugs were additional microscopic features believed to impair venous drainage and to contribute to ischemic necrosis of the alveolar bone. CONCLUSIONS: Primary thrombophilia and hypofibrinolysis appear to be common, heritable, pathophysiologic risk factors for idiopathic osteonecrosis of the jaws. These coagulation defects may also contribute to alveolar neuralgia, atypical odontalgia and facial neuralgia, idiopathic trigeminal neuralgia, and to treatment failures so often encountered in patients with alveolar osteonecrosis and disabling chronic facial and jawbone pain syndromes.

A preliminary pilot study of treatment of thrombophilia and hypofibrinolysis and amelioration of the pain of osteonecrosis of the jaws.

OBJECTIVES: In a preliminary pilot study of 30 treatments in 26 patients with osteonecrosis of the jaws and chronic disabling facial pain, our specific aim was to determine whether, to what degree, and how safely therapy of hypofibrinolysis and thrombophilia would ameliorate the chronic pain associated with osteonecrosis of the mandible and maxilla. STUDY DESIGN: Thrombophilia was treated with Coumadin (DuPont) in 10 patients; hypofibrinolysis was treated with Winstrol (Sanofi-Winthrop) in 20 patients, including 4 who had mixed thrombophilia and hypofibrinolysis and had previously been treated with Coumadin. The initial treatment period was targeted to be 4 months. Each patient was asked to keep a daily written pain-relief numeric rating score and side-effects diary and to provide a summary pain-relief numeric rating score and side effects compilation for the total treatment period. RESULTS: There were 4 men and 22 women in the study group; their mean age was 49 +/- 11 years. The mean onset of their osteonecrosis pain was at age 45 +/- 12 years, and the mean duration of their facial pain prior to therapy was 4.5 +/- 4.2 years. Ten patients had one or more thrombophilic traits (there were two patients with protein C deficiency, five with resistance to activated protein C and/or the mutant Factor V Leiden gene, and four with high anticardiolipin antibodies). The 10 patients who were thrombophilic were treated with Coumadin (the international normalized ratio was targeted to 2.5-3.0) for 22 +/- 9 weeks. By self-reported pain-relief numeric rating scores, 6 of the 10 patients with thrombophilia (60%) had > or = 40% pain relief, 2 (20%) had no change, and 2 (20%) had increased pain (30% and 80% worse). Nine of the 10 patients with thrombophilia (90%) had no Coumadin-related side effects; 1 patient (10%) stopped Coumadin therapy (after 28 weeks) because of nosebleeds. Winstrol (6 mg per day) was used for 16 +/- 9 weeks in 20 patients with hypofibrinolysis, some of whom had one or more hypofibrinolytic traits (10 had high levels of plasminogen activator/inhibitor activity, usually accompanied by low stimulated tissue plasminogen activator activity; 13 had high Lp[a] lipoprotein). Of these 20 patients with hypofibrinolysis, 9 patients (45%) had > or = 40% pain relief, 3 patients (15%) had 20% to 30% relief, 5 patients (25%) had no improvement, and 3 patients (15%) had increased pain (30% worse, 60% worse, and 70% worse). Six of the 20 patients with hypofibrinolysis (30%) had no Winstrol-related side effects, while 14 (70%) had side effects that could be attributed to Winstrol, including weight gain, peripheral edema, increased facial and body hair, and acne--all of which were reversed within 6 weeks of stopping Winstrol therapy. CONCLUSIONS: We postulate that thrombophilia and hypofibrinolysis lead to impaired venous circulation and venous hypertension of the mandible/maxilla with subsequent development of osteonecrosis and chronic facial pain. In many patients, facial pain can be ameliorated by treating the pathogenetic coagulation defects with Coumadin or Winstrol. Large, double-blind, placebo-controlled crossover studies will be required in the future to validate these preliminary results and to determine whether pain relief with Coumadin or Winstrol justifies the risks and side effects associated with these medications, especially for long-term use, in osteonecrosis of the jaws.

History and examination of the orofacial pain patient.

Taking a history and performing an examination on an orofacial pain patient differs significantly from that in the general dental patient. Orofacial pain dentists must be familiar with the disorders that cause chronic head and neck pain. In addition, they must know the pertinent aspects of history taking with regard to the chief complaint, history of the present illness, the relevance of the past medical and dental history and how the social history can act as an important etiologic and prognostic factor. The clinician must also be versed in the elements of the orofacial pain examination which include evaluation of the TMJ and cervical spine; head, neck and dental examination; and, often, neurological and otolaryngological screening. The clinician should also have a familiarity with blood testing, urinalysis and know the uses and limitations of diagnostic imaging.

Interleukin-1beta, interleukin-1 receptor antagonist, and interleukin-1 soluble receptor II in temporomandibular joint synovial fluid from patients with chronic polyarthritides.

PURPOSE: The aim of this study was to investigate whether interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), or soluble IL-1 receptor II (sIL-1RII) in synovial fluid or plasma is associated with joint pain or signs of tissue destruction in patients with temporomandibular joint (TMJ) involvement of polyarthritides. PATIENTS AND METHODS: Forty-three patients with TMJ involvement of polyarthritides were included. TMJ resting pain, tenderness to palpation, pressure pain threshold, pain on mandibular movement, and anterior open bite were assessed. TMJ synovial fluid samples and plasma were obtained for analysis of IL-1beta, IL-1ra, and sIL-1RII. RESULTS: IL-1beta was detected in 18% of the synovial fluid samples and in 44% of the plasma samples. The concentrations of IL-1ra in plasma were lower than in the synovial fluid, whereas the opposite condition was found for sIL-1-RII. IL-1ra in synovial fluid and plasma was associated with low intensity of TMJ pain. sIL-1RII in synovial fluid was associated with low degree of anterior open bite, whereas sIL-1RII in plasma was associated with widespread musculoskeletal pain, TMJ pain and tenderness, and decreased pressure pain threshold over the TMJ. CONCLUSION: IL-1ra and sIL-1RII are present in different proportions in TMJ synovial fluid and blood plasma from patients with TMJ involvement of polyarthritis. Both of these molecules seem to influence the clinical features of these forms of TMJ inflammation.