Peripheral hyperalgesia in experimental neuropathy: exacerbation by neuropeptide Y

Injury of peripheral nerves often results in hyperalgesia (an increased sensitivity to painful stimuli). This hyperalgesia is mediated in part by sympathetic neurotransmitters. We examined the effect of neuropeptide Y (NPY), specific Y1 and Y2 agonists, and an NPY antagonist on peripheral hyperalgesia in rats whose sciatic nerves had been partially transected. NPY and the Y2 agonist, N-acetyl [Leu28,Leu31] NPY 24-36 exacerbated both mechanical and thermal hyperalgesia, while the Y1 agonist, [Leu31, Pro34]NPY relieved thermal hyperalgesia. Mechanical and thermal hyperalgesia were both relieved by alpha-trinositol (PP56), a non-competitive antagonist of the actions of neuropeptide Y. Hyperalgesia was also relieved by surgical sympathectomy, which eliminated the effects of NPY and its agonists. These results suggest that neuropeptide Y contributes to peripheral hyperalgesia by actions at Y2 receptors, which may be located on postganglionic sympathetic terminals.