The effects of intrathecal neuropeptide Y on the spinal nociceptive flexor reflex in rats with intact sciatic nerves and after peripheral axotomy.
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 100 ng) 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 micrograms), 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 the alpha 2 adrenoceptor antagonist atipamezole. Intrathecal neuropeptide Y at doses up to 1 and 10 micrograms 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 microgram/microliter) 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 microgram neuropeptide Y was stronger and longer lasting than in normal rats. Intrathecal neuropeptide Y (100 ng-10 micrograms) 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 and alpha 2-adrenergic systems, it may be mediated by its own receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Xu
X J
XJ
Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Hao
J X
JX
Hökfelt
T
T
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007278:Injections, Spinal; D009412:Nerve Fibers / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D013373:Substance P; D015288:Neurokinin A