Search

Objective: The aim of the present study was to evaluate changes in expression levels of three nitric oxide synthases (NOSs), namely inducible NOS (iNOS), neuronal NOS (nNOS) and endothelial NOS (eNOS), in the subnucleus caudalis of the trigeminal sensory nuclear complex (Vc) under experimental myositis conditions., Design: Male Sprague Dawley rats were injected with an inflammatory agent, complete Freund's adjuvant (CFA), or capsaicin in the masseter muscle. The brainstem region containing the Vc was extracted at both immediate (30 and 60 min) and longer (1, 3, 7 days) time points to examine the changes in the three NOS protein levels via the Western blot technique. Subsequently, the RT-PCR experiments were carried out to verify the changes in iNOS mRNA., Results: Following the injections of CFA, there were no significant changes in the level of the three NOS proteins at the immediate time points. However, there was a significant upregulation of iNOS mRNA and protein 3 days after CFA-induced inflammation. Neither nNOS nor eNOS showed significant changes in the protein level at any of the longer time points. Capsaicin injection in the masseter, which we recently reported to upregulate all three NOS at the immediate time points, did not result in significant changes at longer time points., Conclusion: Acute and chronic muscle inflammation differentially modulates the expression of the three NOS in the Vc. These data suggest that the contribution of each NOS in craniofacial muscle pain processing under inflammatory conditions may be anticipated with distinct temporal profiles., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The NMDA and TRPV1 receptors that are expressed in sensory neurons have been independently demonstrated to play important roles in peripheral pain mechanisms. In the present study, we investigated whether the 2 receptor-channel systems form a functional complex that provides the basis for the development of mechanical hyperalgesia. In the masseter muscle, direct application of NMDA induced a time-dependent increase in mechanical sensitivity, which was significantly blocked when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. The NR1 subunit of the NMDA receptor and TRPV1 were coexpressed in 32% of masseter afferents in trigeminal ganglia (TG). Furthermore, NR1 and NR2B formed protein-protein complexes with TRPV1 in TG as demonstrated by coimmunoprecipitation experiments. Calcium imaging analyses further corroborated that NMDA and TRPV1 receptors functionally interact. In TG culture, application of NMDA resulted in phosphorylation of serine, but not threonine or tyrosine, residues of TRPV1 in a time course similar to that of the development of NMDA-induced mechanical hyperalgesia. The NMDA-induced phosphorylation was significantly attenuated by CaMKII and PKC inhibitors, but not by a PKA inhibitor. Consistent with the biochemical data, the NMDA-induced mechanical hyperalgesia was also effectively blocked when the muscle was pretreated with a CaMKII or PKC inhibitor. Thus, NMDA receptors and TRPV1 functionally interact via CaMKII and PKC signaling cascades and contribute to mechanical hyperalgesia. These data offer novel mechanisms by which 2 ligand-gated channels in sensory neurons interact and reinforce the notion that TRPV1 functions as a signal integrator under pathological conditions., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

In this study, involvement of peripheral AMPA receptors in mediating craniofacial muscle pain was investigated. AMPA receptor subunits, GluR1 and GluR2, were predominantly expressed in small to medium size neurons but more GluR2 positive labeling were encountered in trigeminal ganglia (TG) of male Sprague Dawley rats. A greater prevalence of GluR2 is reflected by the significantly higher percentage of GluR2 than GluR1 positive masseter afferents. Nocifensive behavior and c-fos immunoreactivity were assessed from the same animals that received intramuscular mustard oil (MO) with or without NBQX, a potent AMPA/KA receptor antagonist. Masseteric MO produced nocifensive hindpaw shaking responses that peaked in the first 30s and gradually diminished over a few minutes. There was a significant difference in both peak and overall MO-induced nocifensive responses between NBQX and vehicle pre-treated rats. Subsequent Fos studies also showed that peripheral NBQX pre-treatment effectively reduced the MO-induced neuronal activation in the subnucleus caudalis of the trigeminal nerve (Vc). These combined results provide compelling evidence that acute muscle nociception is mediated, in part, by peripherally located AMPA/KA receptors, and that blockade of multiple peripheral glutamate receptor subtypes may provide a more effective means of reducing muscular pain and central neuronal activation.

Objectives: This placebo‐controlled randomized double‐blinded clinical study assessed the analgesic efficacy of intramuscular morphine in TMD patients with myofascial pain and sex‐dependent responses of the morphine treatment. Subjects and Methods: Men and women with TMD were treated with morphine (1.5 or 5 mg), lidocaine, or saline in the masseter muscle. VAS of pain intensity, PPT, and PPtol were compared between treatment groups and gender. An additional group was treated with morphine in the trapezius muscle to evaluate the systemic effect of morphine that may reduce pain in the masseter muscle. Results: There was a significant difference in VAS scores between the morphine 5 mg group and the saline group favoring morphine, but not between the morphine 5 mg and lidocaine. Morphine 1.5 and 5 mg treatments led to consistently and significantly elevated PPT and PPtol measures in men, but not in women. Morphine administered in the trapezius muscle did not affect the outcome measures. Conclusion: A single dose intramuscular morphine produced analgesic effects up to 48 hr in patients with myofascial pain. Intramuscular morphine elevated mechanical pain threshold and tolerance in the masseter only in male patients, suggesting sex differences in local morphine effects. No systemic effect of intramuscular morphine was detected. [ABSTRACT FROM AUTHOR]

Objective: to investigate the change in volume and signal in the masticatory muscles and temporomandibular joint (TMJ) of patients with temporomandibular disorder (TMD) after whiplash injury, based on magnetic resonance imaging (MRI), and to correlate them with other clinical parameters. Methods: ninety patients (64 women, 26 men; mean age: 39.36 ± 15.40 years), including 45 patients with symptoms of TMD after whiplash injury (wTMD), and 45 age- and sex-matched controls with TMD due to idiopathic causes (iTMD) were included. TMD was diagnosed using the study diagnostic criteria for TMD Axis I, and MRI findings of the TMJ and masticatory muscles were investigated. To evaluate the severity of TMD pain and muscle tenderness, we used a visual analog scale (VAS), palpation index (PI), and neck PI. Results: TMD indexes, including VAS, PI, and neck PI were significantly higher in the wTMD group. In the wTMD group, muscle tenderness was highest in the masseter muscle (71.1%), and muscle tenderness in the temporalis (60.0%), lateral pterygoid muscle (LPM) (22.2%), and medial pterygoid muscle (15.6%) was significantly more frequent than that in the iTMD group (all p < 0.05). The most noticeable structural changes in the masticatory muscles occurred in the LPM with whiplash injury. Volume (57.8% vs. 17.8%) and signal changes (42.2% vs. 15.6%) of LPM were significantly more frequent in the wTMD group than in the iTMD group. The presence of signal changes in the LPM was positively correlated with the increased VAS scores only in the wTMD group (r = 0.346, p = 0.020). The prevalence of anterior disc displacement without reduction (ADDWoR) (53.3% vs. 28.9%) and disc deformity (57.8% vs. 40.0%) were significantly higher in the wTMD group (p < 0.05). The presence of headache, sleep problems, and psychological distress was significantly higher in the wTMD group than in the iTMD group. Conclusion: abnormal MRI findings and their correlations with clinical characteristics of the wTMD group were different from those of the iTMD group. The underlying pathophysiology may differ depending on the cause of TMD, raising the need for a treatment strategy accordingly. [ABSTRACT FROM AUTHOR]