Effects of nerve growth factor experimentally-induced craniofacial muscle sensitization on referred pain frequency and number of headache days: A double-blind, randomized placebo-controlled study.

OBJECTIVE: To assess if repeated intramuscular injections of nerve growth factor into the temporalis and masseter muscles increase mechanical sensitivity and entropy scores. Furthermore, to investigate if increased mechanical sensitivity would lead to increased prevalence of referred pain in the studied individuals. Finally, if increased muscle sensitization would lead to an increase in number of headache days during the experimental period. METHODS: The present double-blind, randomized placebo-controlled study recruited 16 healthy participants who were injected with nerve growth-factor, on 2 days, into the masseter and temporalis muscles and isotonic saline on the contralateral side. Mechanical sensitivity was assessed at seven different time-points (total of 21 days) by application of three different forces to 15 different sites of both muscles. Participants were asked after each force application if they experienced referred pain and were asked to keep a headache diary during the experimental period. RESULTS: In summary, a) repeated intramuscular injections of nerve-growth-factor caused an increase in mechanical sensitivity for the masseter but not the temporalis muscle, and an increase in entropy scores when compared to the isotonic saline side. b) Both referred pain frequency and number of headache days were not increased following nerve-growth-factor injections. CONCLUSIONS: These findings support the idea that mechanical sensitization in the masseter and temporalis muscles differs following injections of nerve growth factor. Furthermore, referred pain and headache frequency do not seem to be related to nerve growth factor sensitization in this model. These findings support the idea that in healthy individuals referred pain may be an epiphenomenon of the muscle in response to noxious input.

Blood oxygenation of masseter muscle during sustained elevated muscle activity in healthy participants.

Myofascial pain associated with temporomandibular disorders has often been linked to pathological muscle hyperactivity. As a result, localised disturbances of intramuscular blood flow could lead to a lower level of oxygen distribution, hypoxia and microcirculatory changes. To assess haemodynamic changes in the masseter muscle during sustained elevated muscle activity (SEMA). Sixteen healthy participants performed thirty 1-min bouts of SEMA with intervals of 1-min 'rest' periods between the bouts on a bite force transducer device. The participants completed three sessions with different percentage of their maximal voluntary occlusal bite force (MVOBF): 0% (no task), 10% or 40% MVOBF tasks. The order of the sessions was randomised with 1- to 2-week intervals. Haemodynamic characteristics of the masseter muscle were estimated with use of a laser blood oxygenation monitor. Tissue blood oxygen saturation (StO2 ) during SEMA was lower than during rest (P < 0·001). The relative changes in total haemoglobin (Total-Hb) and StO2 were influenced by condition (SEMA and rest) and with interactions between condition and session (0%, 10% and 40% MVOBF tasks). These results suggest that SEMA may lead to hypoxia in the masseter muscle and that the haemodynamic characteristics and muscle symptoms depend on the magnitude of muscle contractions. Overall, the present findings may help to provide better insights into relationships between jaw muscle activity, haemodynamic changes and symptom developments with implications for clinical conditions such as bruxism characterised by different levels of tooth-grinding and tooth-clenching muscle activity.

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.

Intramuscular pH modulates glutamate-evoked masseter muscle pain magnitude in humans.

BACKGROUND: This study was conducted to determine whether glutamate-evoked jaw muscle pain is modulated by the acidity and temperature of the solution injected. METHODS: Thirty two participants participated and received injections of high-temperature acidic (HT-A) glutamate (pH 4.8, 48 °C), high-temperature neutral (HT-N) glutamate (pH 7.0, 48 °C) and neutral temperature neutral (NT-N) glutamate (pH 7.0, 38 °C) solutions (0.5 mL) into the masseter muscle. Pain intensity was assessed with an electronic visual analogue scale (eVAS). Numerical rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, mechanical sensitivity and pressure pain thresholds (PPT) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). One or two way ANOVAs were used for data analyses. RESULTS: Injection of HT-A glutamate solutions significantly increased the area under the VAS-time curve compared with injection of HT-N glutamate and NT-N glutamate solution (p < 0.040). The duration of glutamate-evoked pain was significantly longer when HT-A glutamate was injected than when NT-N glutamate was injected (p < 0.017). No significant effects of acidity were detected on pain drawings, NRS unpleasantness and heat perception, but there was a significant effect of acidity on MPQ scores and mechanical sensitivity. CONCLUSION: Acidity and temperature modulate glutamate-evoked jaw muscle pain suggesting an interaction between acid sensing and glutamate receptors which could be of importance for understanding clinical muscle pain conditions.

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.

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.

Craniofacial pain and jaw-muscle activity during sleep.

This study compared the jaw-muscle electromyographic (EMG) activity during sleep in patients with craniofacial pain (n = 63) or no painful conditions (n = 52) and between patients with tension-type headache (TTH: n = 30) and healthy control individuals (n = 30). All participants used a portable single-channel EMG device (Medotech A/S) for four nights. There was no significant difference in EMG activity between craniofacial pain (24.5 ± 17.9 events/hr) and no painful conditions (19.7 ± 14.5), or between TTH (20.8 ± 15.0) and healthy control individuals (15.2 ± 11.6, p >.050). There were positive correlations between EMG activity and number of painful muscles (r = 0.188; p = 0.044), characteristic pain intensity (r = 0.187; p = 0.046), McGill Pain Questionnaire (r = 0.251; p = 0.008), and depression scores (r = 0.291; p = 0.002). Patients with painful conditions had significantly higher night-to-night variability compared with pain-free individuals (p < 0.050). This short-term observational study suggests that there are no major differences between patients with different craniofacial pain conditions and pain-free individuals in terms of jaw-muscle EMG activity recorded with a single-channel EMG device during sleep. However, some associations may exist between the level of EMG activity and various parameters of craniofacial pain. Longitudinal studies are warranted to further explore the relationship between sleep bruxism and craniofacial pain.