Involvement of neuronal, inducible and endothelial nitric oxide synthases in capsaicin-induced muscle hypersensitivity

• Published in: European journal of pain 2009-10, Vol.13 (9), p.924-928
• Main Authors: Lee, Jong-Seok, Zhang, Youping, Ro, Jin Y
• Format: Article
• Language: English
• Subjects: Anesthesia & Perioperative Care; Animals; Capsaicin; Capsaicin - pharmacology; Disease Models, Animal; Enzyme Inhibitors - pharmacology; Hyperalgesia - chemically induced; Hyperalgesia - enzymology; Hyperalgesia - physiopathology; Immunohistochemistry; Male; Masseter Muscle - drug effects; Masseter Muscle - innervation; Masseter Muscle - physiopathology; Muscle pain; Myositis - chemically induced; Myositis - enzymology; Myositis - physiopathology; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - metabolism; Nitric oxide synthases; Pain Medicine; Rat; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Sensory System Agents - pharmacology; Time Factors; Trigeminal; Trigeminal Caudal Nucleus - drug effects; Trigeminal Caudal Nucleus - enzymology; Trigeminal Caudal Nucleus - physiopathology; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 1090-3801; 1532-2149
• DOI: 10.1016/j.ejpain.2008.11.009

Abstract Nitric oxide, which has been implicated in the development of hyperalgesia in the spinal system, has not been systematically studied in the trigeminal system, especially in the context of inflammatory muscle pain condition. In this study, we investigated the functional role of centrally released nitric oxide in the pathogenesis of orofacial muscle pain. Specifically, we examined the contribution of neuronal, inducible and endothelial nitric oxide synthases, nNOS, iNOS and eNOS, respectively, in mediating masseter hypersensitivity under acute inflammatory condition. Time-dependent changes in nNOS, iNOS and eNOS protein expression in the subnucleus caudalis (Vc) were assessed following capsaicin injection in the masseter muscle of male Sprague Dawley rats. The expression of all three nitric oxide synthases was significantly up-regulated 30–60 min following capsaicin stimulation, which paralleled the time course of the development of capsaicin-induced masseter hypersensitivity. Pretreatment with each NOS inhibitor significantly attenuated the masseter hypersensitivity. These data showed that all three NOS in the Vc are functionally important for the development of craniofacial muscle hyperalgesia and suggest that the three NOS are closely orchestrated to regulate the level of nitric oxide under normal and pathologic conditions.