Malin Ernberg

Interleukin-1β in synovial fluid from the arthritic temporomandibular joint and its relation to pain, mobility, and anterior open bite

Abstract Purpose: The purpose of this study was to investigate whether interleukin-1β in synovial fluid or blood plasma is involved in the development of pain or hyperalgesia of the temporomandibular joint (TMJ), as well as reduced mandibular mobility and anterior open bite. Patients and Methods: Twenty-nine patients with TMJ arthritis and seven healthy subjects were studied. VAS measurement of TMJ tenderness on palpation of the TMJ (TDP), TMJ pressure pain threshold and tolerance level (PPTL), mandibular mobility, pain during joint movements, and degree of anterior open bite (AOB) were assessed. IL-1β levels were analyzed in TMJ synovial fluid (SF-IL-1β) and blood samples and correlated with the preceding factors. Results: SF-IL-1β showed significant positive correlations with VAS measurement of pain, TDP, and AOB and a negative correlation with PPTL. Conclusions: This study indicates that IL-1β in the synovial fluid is associated with pain and hyperalgesia in the TMJ region as well as an anterior open bite. Concerning the latter condition, IL-1β seems to be a warning signal of tissue destruction.

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

Abstract 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.

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.

Symptoms and signs of temporomandibular disorders in patients with fibromyalgia and local myalgia of the temporomandibular system. A comparative study.

Symptoms and signs of temporomandibular disorders (TMD) in 46 patients were investigated and compared with those in 20 healthy individuals. Twenty-three patients had fibromyalgia (FM) and 23 had local myalgia (LM). Facial pain was assessed with a visual analogue scale, and a clinical examination was performed, including maximum voluntary mouth opening, temporomandibular joint sounds, tenderness to digital palpation in the masticatory muscles, pressure pain threshold and tolerance level of the superficial masseter muscle, intramuscular temperature, and maximum voluntary bite force. There was a difference in the number of tender muscles between the groups. Pressure pain threshold and tolerance levels were lower in the FM than in the LM group, whereas both showed lower values than a control group (C). The intramuscular temperature and maximum voluntary mouth opening were lower in the patient groups than in the C group. TMJ sounds showed a difference between all three groups. In conclusion, this study shows that FM patients frequently have TMD and indicates several differences between patients with FM and LM with regard to clinical variables.

Effects of low-power laser exposure on masseter muscle pain and microcirculation.

One possible cause of the reported positive treatment effect by low‐power laser exposure in muscle pain conditions could be that it increases the local microcirculation. The aim of this study was therefore to investigate the immediate effects on masseter muscle blood flow by low‐power laser exposure in patients with chronic orofacial pain of muscular origin in comparison to healthy individuals. Twelve patients with myofascial pain of orofacial muscles and 12 age and gender matched healthy individuals participated in the study. Before laser exposure the subjects were examined clinically and the patients scored their current pain intensity from the most tender masseter muscle. Intramuscular laser‐Doppler flowmetry was performed unilaterally in the most tender point (patients) or in a standardized point (healthy subjects) of the masseter muscle. The muscle was first exposed with a Gallium–Aluminum–Arsenide laser (active laser) or placebo laser for 2 min in a randomized and double‐blind manner. After another 8 min the muscle was treated with the other laser for 2 min and the LDF recording continued for 8 min. Finally, the patients again assessed the pain intensity. Data were analyzed blindly by one of the authors not participating in data collection. The pain intensity was not affected by laser exposure. The blood flow did not change significantly in the patients, but increased after active laser exposure and decreased after placebo exposure in the healthy individuals. The difference between active laser and placebo was significant. In conclusion, the results of this study do not support an effect of low‐power laser exposure on masseter muscle microcirculation in patients with chronic orofacial pain of muscular origin.

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

Abstract 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‐HT3 receptor antagonist granisetron or 5‐HT1A 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 30 min. 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 5–8 min. 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.

Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study

&NA; Evidence of an effect by botulinum toxins is still lacking for most pain conditions. In the present randomized, placebo‐controlled, crossover multicenter study, the efficacy of botulinum toxin type A (BTX‐A) was investigated in patients with persistent myofascial temporomandibular disorders (TMD). Twenty‐one patients with myofascial TMD without adequate pain relief after conventional treatment participated. A total of 50 U of BTX‐A or isotonic saline (control) was randomly injected into 3 standardized sites of the painful masseter muscles. Follow‐up was performed after 1 and 3 months, followed by a 1‐month washout period, after which crossover occurred. Pain intensity at rest was the primary outcome measure, while physical and emotional function, global improvement, side effects, and clinical measures were additional outcome measures. There was no main difference between drugs (ANOVA; P = .163), but there was a significant time effect (P < .001), so BTX‐A reduced mean (SD) percent change of pain intensity by 30 (33%) after 1 month and by 23 (30%) after 3 months compared to 11 (40%) and 4 (33%) for saline. The number of patients who received a 30% pain reduction was not significantly larger for BTX‐A than after saline at any follow‐up visit. The number needed to treat was 11 after 1 month and 7 after 3 months. There were no significant changes after treatment in any other outcome measures, with the exception of pain on palpation, which decreased 3 months after saline injection (P < .05). These results do not indicate a clinical relevant effect of BTX‐A in patients with persistent myofascial TMD pain. Botulinum toxin type A is not an effective adjunct to conventional treatment in persistent myofascial temporomandibular disorders.

The Influence of Menstrual Phases on Pain Modulation in Healthy Women

UNLABELLED This study investigated if conditioned pain modulation (CPM) varies across the menstrual cycle in healthy, normally menstruating women and investigated correlations between sex hormone levels and CPM across the menstrual cycle. Thirty-six normally menstruating women were tested during 3 phases of the menstrual cycle: early follicular, ovulatory, and midluteal, confirmed by hormone determinations. Mechanical pressure (test stimulus) was applied to the masseter muscle and the induced pain assessed before, during, and after immersion of the hand into ice water (conditioning stimulus) to activate CPM or tepid water (control). Conditioning pain, ie, pain in the hand during CPM/control experiment, and tolerance time were also measured. Test pain intensity was suppressed during CPM in all phases (P < .001), but with more effective suppression during the ovulatry than during the early follicular phase (P < .05). There were no changes in test pain intensity during the control experiment and no significant differences in conditioning pain, or tolerance time between phases. In conclusion, our results showed more effective pain modulation in the ovulatory phase of the menstrual cycle, when estradiol levels are high and progesterone levels are low, than in the early follicular phase when both these hormones are low. PERSPECTIVE Deficient pain modulation is believed to be an important pathogenic factor in many chronic pain conditions that affect women. This article shows that sex hormones modulate conditioned pain modulation, because pain inhibition was more effective in the ovulatory phase of the menstrual cycle than in the early follicular phase.

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.

Long-term effect on tinnitus by treatment of temporomandibular disorders: a two-year follow-up by questionnaire.

Objective. The aim of the study was to investigate the presence of symptoms and signs of temporomandibular disorders (TMD) in patients with tinnitus and to evaluate the effect of TMD treatment on tinnitus in a long-term perspective in comparison with a control group of patients on a waiting list. Material and Methods. One-hundred-and-twenty patients with tinnitus were subjected to a clinical examination of the masticatory system and whether they had co-existing TMD to TMD treatment. Ninety-six patients had TMD, most frequently localized myalgia. Seventy-three of these completed the treatment and responded to a questionnaire 2 years later. Fifty patients with tinnitus who were on the waiting list served as a control group. Results. Eighty percent of the patients had signs of TMD, most commonly myofascial pain. Forty-three percent of the patients reported that their tinnitus was improved at the 2-year follow-up, 39% that it was unchanged, and 17% that it was impaired compared to before the treatment. Twelve percent of the subjects in the control group reported that their tinnitus was improved compared to 2 years previously, 32% that it was unchanged, and 56% that it was impaired. The difference between groups was significant (χ2: p<0.001). Conclusion. The results of this study showed that TMD symptoms and signs are frequent in patients with tinnitus and that TMD treatment has a good effect on tinnitus in a long-term perspective, especially in patients with fluctuating tinnitus.