Pain sensitivity increases with sleep disturbance under predictable chronic mild stress in mice.

Even though it has been well documented that stress can lead to the development of sleep disorders and the intensification of pain, their relationships have not been fully understood. The present study was aimed at investigating the effects of predictable chronic mild stress (PCMS) on sleep-wake states and pain threshold, using the PCMS rearing conditions of mesh wire (MW) and water (W) for 21 days. Exposure to PCMS decreased the amount of non-rapid eye movement (NREM) sleep during the dark phase. Moreover, the chronicity of PCMS decreased slow-wave activity (SWA) during NREM sleep in the MW and W groups in both the light and dark phases. Mechanical and aversively hot thermal hyperalgesia were more intensified in the PCMS groups than the control. Higher plasma corticosterone levels were seen in mice subjected to PCMS, whereas TNF-α expression was found higher in the hypothalamus in the W and the trigeminal ganglion in the MW group. The W group had higher expression levels of IL-6 in the thalamus as well. The PCMS paradigm decreased SWA and may have intensified mechanical and thermal hyperalgesia. The current study also suggests that rearing under PCMS may cause impaired sleep quality and heightened pain sensation to painful mechanical and aversively hot thermal stimuli.

Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels.

BACKGROUND: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. METHODS: Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. RESULTS: Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. CONCLUSIONS: Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency.

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.

Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders.

AIMS: To investigate the relationship between omentin-1 levels and painful temporomandibular disorders (TMD). METHODS: In a case-control design, chronic painful TMD cases (n = 90) and TMD-free controls (n = 54) were selected from participants in the multisite OPPERA study (Orofacial Pain: Prospective Evaluation and Risk Assessment). Painful TMD case status was determined by examination using established Research Diagnostic Criteria for TMD (RDC/TMD). Levels of omentin-1 in stored blood plasma samples were measured by using an enzyme linked immunosorbent assay. Binary logistic regression was used to calculate the odds ratios (ORs) and 95% confidence limits (CLs) for the association between omentin-1 and painful TMD. Models were adjusted for study site, age, sex, and body mass index. RESULTS: The unadjusted association between omentin-1 and chronic painful TMD was statistically nonsignificant (P = .072). Following adjustment for covariates, odds of TMD pain decreased 36% per standard deviation increase in circulating omentin-1 (adjusted OR = 0.64; 95% CL: 0.43, 0.96; P = .031). CONCLUSION: Circulating levels of omentin-1 were significantly lower in painful TMD cases than controls, suggesting that TMD pain is mediated by inflammatory pathways.

Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model.

Evidence strongly supports that low-level laser therapy (LLLT) is an effective physical modality for the treatment of pain associated with myofascial trigger points (MTrP). However, the effect of laser fluence (energy intensity in J/cm(2)) on biochemical regulation related to pain is unclear. To better understand the biochemical mechanisms modulated by high- and low-fluence LLLT at myofascial trigger spots (MTrSs; similar to human MTrPs) in skeletal muscles of rabbits, the levels of ß-endorphin (ß-ep), substance P (SP), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) were investigated in this study. New Zealand rabbits (2.5-3.0 kg in weight) were used in this study. High-fluence LLLT (27 J/cm(2)), low-fluence LLLT (4.5 J/cm(2)), or sham operations were applied on MTrSs of biceps femoris of rabbits for five sessions (one session per day). Effects of LLLT at two different fluences on biceps femoris, dorsal root ganglion (DRG), and serum were determined by ß-ep, SP, TNF-α, and COX-2 immunoassays. LLLT irradiation with fluences of 4.5 and 27 J/cm(2) at MTrSs can significantly reduce SP level in DRG. LLLT with lower fluence of 4.5 J/cm(2) exerted lower levels of TNF-α and COX-2 expression in laser-treated muscle, but LLLT with higher fluence of 27 J/cm(2) elevated the levels of ß-ep in serum, DRG, and muscle. This study demonstrated fluence-dependent biochemical effects of LLLT in an animal model on management of myofascial pain. The findings can contribute to the development of dosage guideline for LLLT for treating MTrP-induced pain.

Spirituality of chronic orofacial pain patients: case-control study.

The objective of this study was to investigate spirituality and blood parameters associated with stress in patients with facial musculoskeletal pain. Twenty-four women with chronic facial musculoskeletal pain (CFMP) and 24 healthy women were evaluated with a protocol for orofacial characteristics, research diagnostic criteria for temporomandibular disorders and the Spiritual Perspective Scale. Blood samples were collected to analyze blood count, cortisol, ACTH, C3, C4, thyroid hormones, total immunoglobulin, C-reactive protein and rheumatoid factor. The study group was more spiritualized than control group. Individuals with a high score of spirituality had less myofascial pain, less bruxism and fewer complaints. They also had lower levels of ACTH and IgE. Spirituality was higher in the study group and can be considered an important tool for coping with CFMP.

Serial blood serotonin levels in a randomized controlled trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in patients with chronic tension-type facial pain.

BACKGROUND: Patients often present with chronic facial pain despite normal nasal endoscopy and sinus computerized tomography. Such pain has increasingly been recognized as being of neurological origin with one of the commonest underlying causes being mid-facial segmental tension-type pain (MFP) which is a version of tension headache in the face. Descending serotonergic neuronal projections are known to modulate pain and intra-platelet serotonin levels are an accepted model reflecting central intra-neuronal serotonin. OBJECTIVES: 1.To determine whether low-dose amitriptyline significantly changes whole blood serotonin compared to a surrogate placebo in patients with chronic MFP 2. To determine whether the addition of pindolol, a beta blocker with serotonin receptor blocking properties further alters blood serotonin. METHODOLOGY: Sixty-two patients were randomized to three treatment groups a) amitriptyline , b) amitriptyline with pindolol, and c) loratadine as surrogate placebo. Whole blood serotonin was taken before and after 8 weeks of treatment. Serotonin was also measured in 40 age-matched healthy controls. RESULTS: There was a significant reduction in blood serotonin levels in the amitriptyline with pindolol group. A non-significant reduction was seen in the amitriptyline group, with no change in serotonin levels in the surrogate placebo group. A comparison of change in serotonin with change in pain frequency and intensity scores is presented. Women in the control group had significantly higher serotonin levels than men. Women with tension-type facial pain who failed to respond to treatment had significantly lower blood serotonin than women in the control group. CONCLUSION: When linked to the clinical response this study provides evidence that the serotonergic system is involved in the modulation of chronic MFP. Serotonin levels are sex-dependent and related to treatment response.

Plasma levels of milnacipran and its effectiveness for the treatment of chronic pain in the orofacial region.

OBJECTIVES: This study was performed to assess the relationship between plasma levels of milnacipran and its analgesic/antidepressive effect in patients with chronic orofacial pain treated with this drug. METHODS: A total of 44 patients took milnacipran for 12 weeks. Patients were assessed for their pain and depressive symptoms using the visual analog scale (VAS) and Hamilton Depression Rating Scale, respectively. The plasma milnacipran level was also assessed at week 12. RESULTS: Forty patients completed study treatment and were included in the analysis. In these patients, the VAS score at week 12 significantly decreased from the baseline score (t = 5.15, p < 0.0001). The dose of milnacipran was positively correlated in a linear manner with the plasma level of the drug (Y = 44.86 + 0.33X, r = 0.54, R(2) = 0.29, p = 0.0004). A quadratic regression curve was plotted between the percentage of decrease in the VAS score and plasma milnacipran level (Y = 27.39 + 0.76X - 0.008X(2) , p = 0.048, r = 0.40, R(2) = 0.16). On the other hand, no significant relationship was noted between the percentage of decrease in the Hamilton Depression Rating Scale score and plasma milnacipran level. CONCLUSION: The analgesic effect of milnacipran was suppressed in the presence of the plasma level of the drug outside the therapeutic range, whereas its antidepressant effect was not affected by its plasma level.

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.

Neuroendocrine responses to psychological stress in patients with myofascial pain.

AIMS: To investigate the responses of the hypothalamus-pituitary-adrenocortical and sympathetic-adrenal-medullary systems to experimentally induced psychological stress in patients with myofascial pain. METHODS: To characterize the features of these systems, temporal variations in plasma cortisol, adrenaline, and noradrenaline concentrations in response to psychological stress were measured in 20 patients with myofascial pain and in 20 healthy controls. RESULTS: The concentrations of plasma cortisol, adrenaline, and noradrenaline in response to psychological stress were significantly higher in the pain patients than in the healthy controls. Furthermore, although the plasma cortisol, adrenaline, and noradrenaline concentrations were significantly increased from the basal levels in both groups, the rate of recovery from these levels was significantly slower in patients than in healthy controls. CONCLUSION: These results suggest that both the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenocortical systems are more highly activated in response to psychological stress in patients with myofascial pain than in healthy individuals.

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.

Analgesia and COX-2 inhibition.

While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE2 levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB2 at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE2 is temporally related to NSAID analgesia.

Pain mediation by prostaglandin E2 and leukotriene B4 in the human masseter muscle.

The pathophysiology behind chronic pain from masticatory muscles is unclear. Our hypothesis was that this pain is of inflammatory origin and associated with release of inflammatory mediators. The aim of this study was therefore to investigate the presence of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the masseter muscle and plasma and their relation to myalgia. Nineteen patients with fibromyalgia, 19 with local myalgia of the masseter muscle, and 11 healthy individuals were examined with regard to local muscular pain intensity at rest and pressure pain threshold. Inclusion criteria were masseter muscle pain for at least 3 months and masseter muscle tenderness on digital palpation. Samples were obtained from the masseter muscle by microdialysis, and the dialysates and venous blood samples were analyzed with regard to PGE2 and LTB4 concentration. Intramuscular levels were found in all groups, with significantly higher levels of LTB4 in the patients with fibromyalgia, in whom PGE2 was positively correlated to muscular pain. In the healthy individuals PGE2 was negatively correlated to pressure pain threshold. In both patient groups but not in the healthy individuals LTB4 increased during the consecutive samplings. PGE2 and LTB4 were detectable in the plasma of all groups. In conclusion, both PGE2 and LTB4 were found in the human masseter muscle. LTB4 levels are increased on needle trauma in patients with myalgia. PGE2 levels are related to muscular pain in patients with fibromyalgia. Masseter muscle pain therefore seems to be partly of peripheral inflammatory origin in fibromyalgia.

Plasma and serum serotonin levels and their relationship to orofacial pain and anxiety in fibromyalgia.

AIMS: Serum serotonin levels (S-5-HT) have been reported to be reduced in patients with fibromyalgia and to show a negative correlation with pain. We hypothesized that one mechanism behind this could be that platelets are activated to release 5-HT into the plasma compartment (P-5-HT), which then binds to nociceptors. The aims of this study were therefore to investigate the relation between P-5-HT and S-5-HT and their relationship versus orofacial pain and anxiety in fibromyalgia. METHODS: Twelve patients with fibromyalgia, 12 patients with rheumatoid arthritis, and 12 healthy individuals participated in the study. Pain measures used were pain intensity assessed with a visual analog scale, pain drawings, and influence of pain on daily living activities (ADL). The Spielberger State and Trait Anxiety Inventory (STAI) scale was used for self-rating of anxiety levels. The participants were examined clinically, and the pressure pain threshold (PPT) over the masseter muscle was assessed. Finally, venous blood was collected for analysis of P-5-HT and S-5-HT. RESULTS: The ratio between P-5-HT and S-5-HT was calculated to determine the relative plasma fraction of serotonin (RPS). Patients with fibromyalgia showed significantly lower S-5-HT than did patients with rheumatoid arthritis. They also showed significantly higher STAI scores and tender point index of orofacial muscles and significantly lower PPT than the healthy individuals. High RPS was associated with high ADL and STAI scores. CONCLUSION: This study indicates that a high level of plasma serotonin in relation to serum level is associated with pain discomfort and increased anxiety in fibromyalgia.

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.

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.

Pain, allodynia, and serum serotonin level in orofacial pain of muscular origin.

AIMS: This study was conducted to investigate the serum level of serotonin (S-5-HT) in patients with temporomandibular disorders (TMD) of muscular origin, i.e., localized myalgia, and to compare it to that found in healthy individuals and patients with fibromyalgia. A second aim was to investigate the association between S-5-HT and pain parameters. METHODS: Twenty patients with localized myalgia participated in the study. Twenty age- and gender-matched healthy individuals and twenty patients with fibromyalgia served as controls. The participants were examined clinically as to the condition of the temporomandibular region and S-5-HT. RESULTS: The levels of S-5-HT did not differ significantly between the groups. However, in patients with localized myalgia there was a negative correlation between S-5-HT and tenderness of the temporomandibular muscles. CONCLUSION: The results of this study indicate that allodynia of orofacial muscles in patients with TMD is significantly related to S-5-HT concentration.

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.

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.

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.