Role of soluble guanylate cyclase in the trigeminal subnucleus caudalis in capsaicin-induced muscle hypersensitivity.

Nitric oxide (NO) produces its effects by activating soluble guanylate cyclase (sGC). In the present study, we investigated the potential role of sGC in the subnucleus caudalis (Vc) in mediating masseter hypersensitivity under acute inflammatory condition in male Sprague-Dawley rats. First, our Western blot analysis revealed that sGC protein is reliably detected in the Vc. Subsequent immunohistochemical studies demonstrated that neuronal cell bodies in the superficial laminae of the Vc positively stained for sGC. Astrocytes in deeper lamina of the Vc also showed sGC immunoreactivity. We then tested whether intrathecal administration of sGC inhibitors, methylene blue (MB), and ODQ, in the Vc, attenuates masseter hypersensitivity induced by intramuscular injection of capsaicin. Intrathecal MB or ODQ significantly blocked the capsaicin-induced reduction of mechanical threshold to noxious stimulation of the masseter. These data indicate that the NO-sGC pathway in the Vc is involved in mediating orofacial muscle hypersensitivity under acute inflammatory conditions.