Neurophysiological evidence for increased kappa opioidergic control of spinal cord neurons in rats with unilateral inflammation at the ankle.
The role of the endogenous kappa opioid system in the control of neuronal activity has been studied in the spinal cord of normal rats and in rats with Freund's adjuvant induced unilateral inflammation of the ankle under barbiturate anaesthesia. During recordings from neurons with ankle input the kappa receptor agonist U50,488H and/or the kappa antagonist nor-binaltorphamine were administered ionophoretically using multibarrel electrodes. In most neurons tested U50,488H reduced the responses evoked by pressure applied across the ankle whereas smaller proportions of neurons showed increased activity or were not affected. The kappa opioid antagonist nor-binaltorphamine affected more neurons in rats with inflammation than in control rats. Ongoing activity was increased in 7 of 19 (37%) neurons in control rats, in 16 of 24 (67%) neurons in the acute phase of inflammation (2 days post inoculation) and in 15 of 23 (65%) neurons in the chronic phase of inflammation (16-20 days post inoculation). During application of nor-binaltorphamine in control rats, the responses to pressure were increased in 9 cells (36%), reduced in 7 cells (28%) and unaffected in 9 cells (36%). In the acute phase of inflammation significantly more neurons (11 of 15, 73%) showed enhanced responses to pressure during ionophoresis of nor-binaltorphamine but not in the chronic phase. These results show that spinal cord neurons with ankle input are influenced by the endogenous kappa opioid system particularly under inflammatory conditions. The upregulation of this system under inflammatory conditions may serve to counteract inflammation-induced hyperexcitability.
Stiller
R U
RU
Physiologisches Institut, Universität Würzburg, Germany.
Grubb
B D
BD
Schaible
H G
HG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D005620:Freund's Adjuvant; D007249:Inflammation / Q000503:physiopathology; D007596:Joints / Q000294:innervation; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013116:Spinal Cord / Q000502:physiology / Q000503:physiopathology*; D013314:Stress, Mechanical
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D005620:Freund's Adjuvant