The effects of intrathecal neuropeptide Y on the spinal nociceptive flexor reflex in rats with intact sciatic nerves and after peripheral axotomy

Abstract

We examined the effects of intrathecally administered neuropeptide Y on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves, or 11–39 days after unilateral transection of the sciatic nerve. In rats with intact sciatic nerve, intrathecal neuropeptide Y at low doses (10 and 100ng) caused a brief facilitation of the flexor reflex. At a dose of 300 ng, the effect of neuropeptide Y on the flexor reflex was biphasic i.e. a brief facilitation followed by slight depression. At higher doses (1 and 10 μg), the effect of neuropeptide Y was mainly inhibitory, causing substantial and usually prolonged depression of the flexor reflex magnitude. The reflex depression caused by intrathecal neuropeptide Y was not reversed by the opioid antagonist naloxone or theα₂ adrenoceptor antagonist atipamezole. Intrathecal neuropeptide Y at doses up to 1 and 10μg had no effect on reflex facilitation caused by conditioning stimulation of C-fibers, intrathecal substance P or neurokinin A. Topical application of neuropeptide Y (1 μg/μl) failed to influence the monosynaptic reflex in normal rats.

Eleven to 16 days after peripheral axotomy, the initial excitation of the flexor reflex to intrathecal neuropeptide Y was significantly enhanced in axotomized compared with normal rats. However, the depressive effect of neuropeptide Y on the flexor reflex was unchanged. Neuropeptide Y did not influence the monosynaptic reflex in axotomized rats at this period. In experiments performed on rats in which the sciatic nerve had been transected 31–39 days previously, the facilitatory effect of neuropeptide Y on the flexor reflex remained enhanced compared with normal rats. Furthermore, the inhibitory effect of neuropeptide Y also increased as 100 ng intrathecal neuropeptide Y was able to produce reflex depression in a similar fashion as 300 ng neuropeptide Y normally and the reflex depression caused by 1 μg neuropeptide Y was stronger and longer lasting than in normal rats. Intrathecal neuropeptide Y (100 ng-10 μg) in rats with intact sciatic nerves caused a moderate decrease in spinal cord dorsal surface blood flow as measured with a laser Doppler flowmeter. This effect of neuropeptide Y was unchanged in axotomized rats.

The present results support previous observations that spinal application of neuropeptide Y in normal rats caused antinociception. As the depressive effect of neuropeptide Y is independent of spinal opioid andα₂-adrenergic systems, it may be mediated by its own receptors. The biphasic effect of neuropeptide Y may reflect its action on different subtypes of neuropeptide Y receptors. Experiments with neuropeptide Y receptor antagonists are required to further define the role of endogenous neuropeptide Y in nociception normally and after peripheral axotomy.