| Evidence from our laboratory suggests that neuropeptide Y (NPY) acts at the NPY Y1 receptor to inhibit thermal hyperalgesia associated with persistent inflammation. We hypothesize that the NPY Y1 receptor also plays an integral part in mediating the antinociceptive effects of NPY in spontaneous pain associated with acute inflammation. Therefore, we investigated the effect of NPY on formalin-evoked nocifensive behaviors and cardiovascular responses, and NPY's antinociceptive activity at a cellular level. NPY inhibited behavioral and cardiovascular responses to intraplantar formalin in a dose-dependent manner. The inhibitory effects of intrathecal NPY were partially reversed by the NPY Y1 receptor antagonist, but not the NPY Y2 receptor antagonist, suggesting that the NPY Y1 receptor plays an important role in mediating inhibition of spinal nociceptive processing. Finally, NPY significantly reduced NK-1 receptor internalization, suggesting that intrathecal NPY inhibits central noxious stimulus-evoked release of Substance P (SP), leading to inhibition of spinal nociceptive transmission. |
