Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy.

The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P < 0.041), whereas IL-1ß was lower (P < 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P = 0.004), while IL-1ß had increased in the relaxation group (P = 0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.

Increased levels of intramuscular cytokines in patients with jaw muscle pain.

BACKGROUND: The aim of this study was to investigate cytokine levels in the masseter muscle, their response to experimental tooth-clenching and their relation to pain, fatigue and psychological distress in patients with temporomandibular disorders (TMD) myalgia. METHODS: Forty women, 20 with TMD myalgia (Diagnostic Criteria for TMD) and 20 age-matched healthy controls participated. Intramuscular microdialysis was performed to sample masseter muscle cytokines. After 140 min (baseline), a 20-minute tooth-clenching task was performed (50% of maximal voluntary contraction force). Pain (Numeric rating scale 0-10) and fatigue (Borg's Ratings of Perceived Exertion 6-20) were assessed throughout microdialysis, while pressure-pain thresholds (PPT) were assessed before and after microdialysis. Perceived stress (PSS-10) and Trait Anxiety (STAI) were assessed before microdialysis. RESULTS: The levels of IL-6, IL-7, IL-8 and IL-13 were higher in patients than controls (Mann Whitney U-test; P's < 0.05) during the entire microdialysis. IL-6, IL-8 and IL-13 changed during microdialysis in both groups (Friedman; P's < 0.05), while IL-1ß, IL-7 and GM-CSF changed only in patients (P's < 0.01). IL-6 and IL-8 increased in response to tooth-clenching in both groups (Wilcoxon test; P's < 0.05), while IL-7, IL-13 and TNF increased only in patients (P's < 0.05). Patients had higher pain and fatigue than controls before and after tooth-clenching (P < 0.001), and lower PPTs before and after microdialysis (P < 0.05). There were no correlations between cytokine levels, pain or fatigue. Also, there were no differences in stress or anxiety levels between groups. CONCLUSIONS: In conclusion, the masseter levels of IL-6, IL-7, IL-8 and IL-13 were elevated in patients with TMD myalgia and increased in response to tooth-clenching. Tooth-clenching increased jaw muscle pain and fatigue, but without correlations to cytokine levels. This implies that subclinical muscle inflammation may be involved in TMD myalgia pathophysiology, but that there is no direct cause-relation between inflammation and pain.

The role of molecular pain biomarkers in temporomandibular joint internal derangement.

There is evidence that low-grade inflammation may be responsible for pain and development of degenerative changes in temporomandibular joint internal derangement. This article reviews the current knowledge of the molecular mechanisms behind TMJ internal derangements. A non-systematic search was carried out in PubMed, Embase and the Cochrane library for studies regarding pathophysiological mechanisms behind internal derangements focusing on pain-mediating inflammatory and cartilage-degrading molecules. Recent data suggest that release of cytokines may be the key event for pain and cartilage destruction in TMJ internal derangements. Cytokines promote the release of matrix metalloproteinases (MMPs), and due to hypoxia, vascular endothelial growth factor (VEGF) is released. This activates chondrocytes to produce MMPs and reduce their tissue inhibitors (TIMPs) as well as the recruitment of osteoclasts, ultimately leading to cartilage and bone resorption. Also, proteoglycans have an important role in this process. Several cytokines, MMPs, TIMPs and VEGF have been identified in higher concentrations in the TMJ synovial fluid of patients with painful internal derangements and shown to be associated with the degree of degeneration. Other molecules that show elevated levels include hyaluronic acid synthase, disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), aggrecan, fibromodulin, biglycan and lumican. Taken together, more or less pronounced inflammation of TMJ structures with release of cytokines, MMPs and other molecular markers that interact in a complex manner may be responsible for tissue degeneration in internal derangements. As internal derangements may be symptom-free, the degree of inflammation, but also other mechanisms, may be important for pain development.

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.

Increased pain and muscle glutamate concentration after single ingestion of monosodium glutamate by myofascial temporomandibular disorders patients.

BACKGROUND: A randomized, double-blinded, placebo-controlled study was conducted to investigate if single monosodium glutamate (MSG) administration would elevate muscle/serum glutamate concentrations and affect muscle pain sensitivity in myofascial temporomandibular disorders (TMD) patients more than in healthy individuals. METHODS: Twelve myofascial TMD patients and 12 sex- and age-matched healthy controls participated in two sessions. Participants drank MSG (150 mg/kg) or NaCl (24 mg/kg; control) diluted in 400 mL of soda. The concentration of glutamate in the masseter muscle, blood plasma and saliva was determined before and after the ingestion of MSG or control. At baseline and every 15 min after the ingestion, pain intensity was scored on a 0-10 numeric rating scale. Pressure pain threshold, pressure pain tolerance (PPTol) and autonomic parameters were measured. All participants were asked to report adverse effects after the ingestion. RESULTS: In TMD, interstitial glutamate concentration was significantly greater after the MSG ingestion when compared with healthy controls. TMD reported a mean pain intensity of 2.8/10 at baseline, which significantly increased by 40% 30 min post MSG ingestion. At baseline, TMD showed lower PPTols in the masseter and trapezius, and higher diastolic blood pressure and heart rate than healthy controls. The MSG ingestion resulted in reports of headache by half of the TMD and healthy controls, respectively. CONCLUSION: These findings suggest that myofascial TMD patients may be particularly sensitive to the effects of ingested MSG. WHAT DOES THIS STUDY ADD?': Elevation of interstitial glutamate concentration in the masseter muscle caused by monosodium glutamate (MSG) ingestion was significantly greater in myofascial myofascial temporomandibular disorders (TMD) patients than healthy individuals. This elevation of interstitial glutamate concentration in the masseter muscle significantly increased the intensity of spontaneous pain in myofascial TMD patients.

NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors.

Intramuscular injection of nerve growth factor (NGF) in healthy humans mimics some of the symptoms of myofascial temporomandibular disorders (M-TMD). We hypothesized that NGF induces a prolonged myofascial mechanical sensitization by increasing peripheral N-methyl-d-aspartate (NMDA) receptor expression, leading to an enhanced response of muscle nociceptors to endogenous glutamate. Behavioral experiments with an injection of NGF (25 µg/ml, 10 µl) into the masseter muscle reduced the mechanical withdrawal threshold for 1 day in male rats and 5 days in female rats. These results mirror the sex-related differences found in NGF-induced mechanical sensitization in humans. Intramuscular injection with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV, 0.020 g/ml, 10 µl) reversed the mechanical sensitization in male but not in female rats. NGF increased the number of NMDA receptor subtype 2B (NR2B)-expressing rat trigeminal masseter ganglion neurons in both sexes, which peaked at 3 days post injection. There was an association between the levels of NR2B expression and NGF-induced mechanical sensitization. The average soma size of NR2B-expressing neurons increased significantly. Increased expression of neuropeptides (CGRP and SP) was observed in NR2B-expressing masseter ganglion neurons in female but not in male rats. In healthy men and women, comparable basal expression levels of NR2B and SP were found in peripheral fibers from masseter muscle microbiopsies. This study suggests that NGF-induced sensitization of masseter nociceptors is mediated, in part, by enhanced peripheral NMDA receptor expression. Measurement of peripheral NMDA receptor expression may be useful as a biomarker for M-TMD pain.

Salivary cortisol and psychological factors in women with chronic and acute oro-facial pain.

The aim of this study was to compare the salivary cortisol level, pain intensity and psychological factors between patients with chronic and acute oro-facial pain (OP) and pain-free subjects. Twenty-seven females with chronic OP (a diagnosis of myofascial pain according to the Research Diagnostic Criteria for Temporomandibular Disorders with at least 6 months duration), 24 females with acute OP (<10 days duration) and 27 pain-free females participated. Morning saliva was collected from all participants for analyses of the cortisol level. The pain intensity was assessed on a 0-10 numeric rating scale. The participants were evaluated by the Symptom Checklist 90-revised for levels of depression and somatisation, and the Perceived Stress Scale. The cortisol levels among the three patient groups were similar with no significant group differences. The median (interquartile range) current pain level did not differ between chronic and acute OP and was, respectively, 5 (4) and 5 (3). Patients with chronic OP showed significantly higher scores for depression, somatisation and perceived stress compared with patients with acute OP (Ps < 0.001), but there were no significant differences between acute OP and controls. To conclude, there were no differences in cortisol level between groups, despite significant higher levels of depression, somatisation and perceived stress in patients with chronic OP. This shows that psychological distress has a more important role in chronic than in acute OP. However, the relation between pain, adreno-cortical activity and psychological distress is complex and warrants further investigation.

Acidic saline-induced pain as a model for experimental masseter myalgia in healthy subjects.

BACKGROUND: Repeated injection of acidic saline into skeletal muscles of the leg in rodents induces a prolonged bilateral mechanical hyperalgesia that persists for up to 30 days and may be useful to model widespread muscle pain conditions. In this study, repeated injection of acidic (pH 3.3) saline solution into the masseter muscle of healthy human subjects was undertaken to determine if these injections are painful and whether they would induce a prolonged period of muscle sensitization to artificial and/or natural mechanical stimulation of the masseter and temporalis muscles. METHODS: Eighteen subjects (10 male, 8 female) participated in the study. Subjects received two injections of 0.5 mL acidic or regular isotonic saline 2 days apart, in a randomized, double blind, crossover design. RESULTS: There was no significant difference in pain intensity ratings when acidic saline injections were compared with regular saline injections. Pain area drawings were, however, significantly larger in response to the first injection of acidic saline than to the second injection of acidic saline or to either the first or second injection of regular saline. Repeated injection of acidic saline did not significantly alter pressure pain thresholds from the masseter or temporalis muscles on either the injected side or the opposite side over the 10-day post injection monitoring period. There was also no effect of injections on chewing. CONCLUSION: These findings indicate that, unlike in some rodent models, repeated injection of low pH solutions into jaw muscles of humans fails to induce a period of prolonged muscle hyperalgesia.

Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P < 0·05) compared with the side pre-treated with control. A subgroup analysis showed that the effect of granisetron on pain duration was significant only in women (P < 0·001), while the effect on peak pain and pain area were significant in both sexes. The results showed no significant change in PPT. In conclusion, these results indicate that granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection.

Experimental myalgia induced by repeated infusion of acidic saline into the human masseter muscle does not cause the release of algesic substances.

BACKGROUND: Animal studies have shown that two repeated intramuscular injections of acidic saline induce mechanical allodynia that lasts for 4 weeks with spread to the contralateral side. In this study, we tested the hypothesis that two repeated intramuscular infusions of acidic saline into the human masseter muscle is associated with pain, mechanical allodynia and release of algesic substances. Eighteen healthy volunteers participated. On day 1, 2.5 mL of acidic saline (pH 3.3) was infused into one of the masseter muscles and isotonic saline (pH 6.0) into the other (randomized and single-blind). Two days later, intramuscular microdialysis was performed to sample serotonin, glutamate, pyruvate, lactate and glucose, during which the saline infusions were repeated. Pain and pressure pain thresholds (PPTs) were recorded before and after infusions on both days. RESULTS: Pain intensity induced by the infusions was higher after acidic than that after isotonic saline (p < 0.05). PPTs were decreased on both sides after microdialysis compared with baseline day 1 (p's < 0.05), but there were no differences in PPTs between sides at any time point. The levels of serotonin, glutamate, pyruvate, lactate or glucose did not change significantly during microdialysis. CONCLUSION: Infusion of acidic saline caused low levels of muscle pain, but no mechanical allodynia and no increased release of algesic substances. The value of this model appears modest, but future studies could be performed with larger sample size and higher flow rate before definite conclusions about the validity of the model for craniofacial myalgia can be drawn.

Orofacial pain and dysfunction in children with juvenile idiopathic arthritis: a case-control study.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) frequently causes temporomandibular joint (TMJ) inflammation. The aim of this study was to evaluate the presence of orofacial pain and temporomandibular dysfunction in patients with JIA and controls. METHODS. Forty-one patients with JIA and 41 age- and sex-matched healthy controls participated. Subjects were asked about facial pain variables and their influence on daily life. A clinical examination was performed. Panoramic radiograph and medical data were extracted from the records. RESULTS: Thirty-three of the JIA patients reported TMJ or facial pain compared to four of the controls (p < 0.001). Nine of the JIA patients, compared to none of the controls, reported that their orofacial symptoms influenced daily life severely (p < 0.001). Clinical findings were more prevalent in JIA (p < 0.001). The assessments of disease activity correlated to palpation pain of jaw muscles (p < 0.001) whereas the presence of structural TMJ changes correlated to reduced jaw opening (p < 0.001). CONCLUSIONS: TMJ pain was prevalent in patients with JIA and influenced daily life severely for nearly a quarter of them. Collaboration between medical and dental care is therefore important.

Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity.

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

Changes in jaw muscle EMG activity and pain after third molar surgery.

Limited jaw-opening capacity is frequently encountered following third molar surgery and may impair function. The aim of this study was to investigate the electromyographic (EMG) activity in jaw muscles after third molar surgery to obtain more insight into the mechanisms of restrictions in jaw opening. Twenty subjects were examined before, 24 h and 1 week after surgery. Ten healthy controls were subjected to the same examination at two different occasions for intersession variability. The EMG activity of the masseter and anterior digastricus muscles was recorded at different jaw positions and during maximum voluntary clenching. Pain intensity was assessed at rest and during movements. The EMG activity in the jaw muscles increased with opening level (P < 0.01), but did not change after surgery. In contrast, the EMG activity during clenching was decreased in all muscles after surgery (P < 0.05). The pain intensity after surgery increased with jaw opening level (P < 0.001), but was in general not correlated to EMG level. Pain intensity during clenching was increased after surgery (P < 0.001), but not correlated to EMG level. The EMG activity did not change between visits in the control group. In conclusion, the results indicate that third molar surgery does not influence the EMG activity in the masseter and anterior digastricus muscles during various levels of static jaw opening, but decreases the EMG activity during clenching. However, these changes are not influenced by pain intensity. The results have implications for the understanding of the phenomenon of trismus.

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.

Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle.

We have previously reported that intramuscular injection of serotonin (5-HT) into the masseter muscle elicits pain and allodynia/hyperalgesia in healthy subjects. The aim of this study was to investigate whether the 5-HT(3) receptor antagonist granisetron or 5-HT(1A) receptor antagonist propranolol can reduce 5-HT induced pain and allodynia/hyperalgesia in the masseter muscle. Twenty-four healthy individuals (12 males and 12 females) without pain from the masseter muscle region participated. They were examined clinically including tenderness to digital palpation (TDP) and pressure pain threshold (PPT) of the masseter muscle. 5-HT in combination with granisetron or propranolol was randomly injected on one side in a double-blind manner. 5-HT in combination with saline was used on the contralateral side. After the injections the pain intensity and PPT were recorded 10 times during 30min. After the last recording the TDP was assessed again. The injections were repeated with the other antagonist within 1 week. All three combinations of substances elicited pain after injection, which lasted for 5-8min. 5-HT induced significantly more pain than granisetron+5-HT and propranolol+5-HT. The TDP increased significantly after injection of all combinations of substances, but there was no significant difference between them. The PPT decreased significantly after injection of 5-HT and increased significantly after injection of granisetron+5-HT, while it did not change significantly after injection of propranolol+5-HT. The difference between 5-HT and granisetron+5-HT was significant. In conclusion, the results of this study indicate that injection of granisetron and propranolol into the human masseter muscle reduces pain induced by local administration of 5-HT, but that the effect of granisetron is stronger than that of propranolol. In addition, granisetron totally abolishes allodynia/hyperalgesia.

Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy individuals.

The aim of this study was to investigate the effect of injection of serotonin (5-HT) into the masseter muscle on pain and allodynia/hyperalgesia. Twelve female patients with fibromyalgia (FM) and 12 age-matched female healthy individuals (HI) participated in the study. The current pain intensity (CPI) and the pressure pain threshold (PPT) of the superficial masseter muscles were assessed bilaterally. 5-HT in one of three randomized concentrations (10(-3), 10(-5), 10(-7) M) or isotonic saline was then injected into either of the two masseter muscles in a double-blind manner. After the injections the CPI and PPT were recorded ten times during 30 min. The injections were repeated twice with the other concentrations of 5-HT after 1 and 2 weeks, respectively. In the FM-group there was a non-significant increase of CPI after injection that lasted during the entire 30-min period irrespective of whether 5-HT or saline was injected. Neither did the PPT change significantly. In the HI-group pain developed significantly after injection irrespective of whether 5-HT or saline was injected, but significantly more so after 5-HT at 10(-3) M than saline injection. CPI decreased quickly and then remained on a very low level for most of the experiment. 5-HT at both 10(-5) M and 10(-3) M caused a significantly greater decrease of PPT than saline. In conclusion, our results show that 5-HT injected into the masseter muscle of healthy female subjects elicits pain and allodynia/hyperalgesia, while no such responses occur in patients with 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.

Effect of 5-hydroxytryptamine-2 and alpha-adrenergic receptor antagonists on the 5-hydroxytryptamine-induced decrease in rabbit masseter muscle blood flow.

A previous study showed a significant decrease in blood flow in the rabbit masseter during infusion of 5-hydroxytryptamine (5-HT) (10(-9) mol/l). The aim of the present study was to test the hypothesis that blockade of the 5-HT2 or the alpha-adrenergic receptor would inhibit the 5-HT-induced decrease of microcirculatory blood flow in the masseter. In 12 rabbits, the masseters were infused with 5-HT (10(-9) mol/l) in combination with the alpha-adrenoceptor antagonist phentolamine (10(-6) mol/l) or the 5-HT2-receptor antagonist ritanserin (10(-6) mol/l). The effect on microcirculatory blood flow was measured by laser-Doppler flowmetry. Infusion of 5-HT induced a significant decrease in blood flow. Inclusion of ritanserin in the 5-HT infusion solution significantly inhibited this decrease, while inclusion of phentolamine did not. This study therefore showed that the 5-HT2 receptor antagonist ritanserin inhibited the 5-HT-induced decrease in microcirculatory blood flow in the rabbit masseter. This decrease in blood flow is thus mediated by the 5-HT2 receptor.

The level of serotonin in the superficial masseter muscle in relation to local pain and allodynia.

The aim of this study was to investigate if serotonin is present in the human masseter muscle and if so, whether it is involved in the modulation of local muscle pain or allodynia. Thirty-five patients with pain and tenderness of the masseter muscle as well as ten healthy individuals were included in the study. Of the patients, 18 suffered from fibromyalgia and 17 had localized myalgia, e.g. myofascial pain in the temporomandibular system. The participants were examined clinically with special consideration to the masseter muscle and the pressure pain threshold as well as tolerance levels of this muscle were assessed. Intramuscular microdialysis was performed in order to sample serotonin and a venous blood sample was collected for analysis of the serum level of serotonin. Serotonin was present in the masseter muscle and the level was significantly higher in the initial sample than in the sample collected during steady state. The level of serotonin in the masseter muscle in relation to the level of serotonin in the blood serum was calculated. This fraction of serotonin was higher in the patients with fibromyalgia than in healthy individuals and high level of serotonin was associated with pain as well as allodynia of the masseter muscle. In conclusion, the results of this study show that serotonin is present in the human masseter muscle both immediately following puncture and in a subsequent steady state and that it is associated with pain and allodynia. The origin of the serotonin seems partly to be the blood, but our results indicate that peripheral release also occurs.

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.