Peripheral hyperalgesia in experimental neuropathy: mediation by alpha 2-adrenoreceptors on post-ganglionic sympathetic terminals.

Rats in which the sciatic nerve is partially transected develop hyperalgesia which is relieved by sympathectomy. We carried out experiments using this model of experimental peripheral neuropathy to examine the peripheral mechanisms underlying sympathetically maintained pain. Subcutaneous injection of noradrenaline (NA) into the affected paw exacerbated the hyperalgesia but had no effect in control animals. Injection of the non-specific alpha-adrenergic blocker phentolamine and the alpha 2-adrenergic blocker yohimbine significantly relieved the hyperalgesia, while injection of the alpha 1-adrenergic blocker prazosin had no effect. Peripheral injection of the alpha 2-adrenergic agonist clonidine had no significant effect, while injection of the alpha 1-adrenergic agonist phenylephrine produced slight exacerbation of mechanical hyperalgesia. Hyperalgesia was eliminated by peripheral injection of indomethacin into the affected paw. Following a chemical sympathectomy, hyperalgesia was eliminated and injection of NA into the hyperalgesic paw had no effect on pain thresholds. We concluded that NA exacerbates hyperalgesia in this experimental model by acting on alpha 2-adrenoreceptors which are located on post-ganglionic sympathetic terminals. Our results are consistent with the proposal (Levine et al. 1986) that activation of these adrenoreceptors brings about an increased release of prostaglandins which sensitises nociceptors.

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.