Involvement of phosphorylated extracellular signal-regulated kinase in the mouse substance P pain model.

In the present study, we investigated the role of pERK in nociceptive processing at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain model. In the immunoblot assay, intrathecal (it) injection with SP increased pERK level at the spinal cord and an immunohistochemical study showed that increase of pERK immunoreactivity mainly occurred in the lamina I and II areas of the spinal dorsal horn. At the supraspinal level, pERK was increased in hippocampus and hypothalamus by i.t. SP injection, and an increase of pERK immunoreactivity mainly occurred in the dentate gyrus and CA3 region of hippocampus and paraventricular nucleus on hypothalamus. The nociceptive behavior induced by Sub P administered either i.t. or intracerebroventricularly (i.c.v.) was attenuated by PD98059 (a MEK 1/2 inhibitor) in a dose-dependent manner. Our results suggest that pERK located at both spinal cord and supraspinal levels plays as an important regulator during the nociceptive process activated by SP administered it.