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Updated: Jun 27, 2026

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx
Published on: May 2, 2025
Involvement of neuronal, inducible and endothelial nitric oxide synthases in capsaicin-induced muscle
Jong-Seok Lee1, Youping Zhang, Jin Y Ro
1Department of Neural and Pain Sciences, University of Maryland Baltimore, School of Dentistry, Baltimore, MD 21201, USA.
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.
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