Peripheral AMPA receptors contribute to muscle nociception and c-fos activation

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.