Comparative study of the analgesic and paralytic effects induced by intrathecal dynorphin a in rats.
Intrathecal injection of dynorphin A produced dual effects on sensory and motor functions in the spinal cord of the rat. At a dose of 5 nmol, dynorphin A produced an increase in tail flick latency (TFL) as well as a reversible motor paralysis as assessed by change in the angle of inclined plane. At a dose of 10 or 20 nmol, dynorphin produced a motor paralysis lasting for up to 24 hours. The effect of dynorphin A on the sensory function of the spinal cord was shown by an increase in the vocalization threshold induced by electrical stimulation of the tail, at dose range of 1.25-10 nmol, with a quick onset (5 min) and relatively short duration (within 60 min). Unlike tail flick reaction which involves spinal motor function, tail stimulation-induced vocalization threshold is a relatively pure index for spinal nociceptive activities. The differential effect of dynorphin on sensory and motor function was supported by the evidence that (1) dynorphin-induced analgesic effect (increase in vocalization threshold) was naloxone reversible, whereas dynorphin-induced motor paralysis was naloxone resistant. (2) Nor-BNI, a specific antagonist for kappa opioid receptor, blocked the sensory effect of dynorphin, but had no influence on motor effect of dynorphin. It is thus concluded that dynorphin has both analgesic and paralytic effects in spinal cord. The analgesia shown by an increase of vocalization threshold is an opioid effect, most probably mediated by kappa opioid receptor; the paralytic effect, however, is a non-opioid effect. The increase of TFL induced by dynorphin involves both sensory (analgesia) and motor (paralysis) effects.
Xue
J C
JC
Neuroscience Research Center, Beijing Medical University, China.
Yu
Y X
YX
Han
J S
JS
Jen
M F
MF
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004399:Dynorphins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D009292:Narcotic Antagonists; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins