Effects of selective and non-selective kappa-opioid receptor agonists on cutaneous C-fibre-evoked responses of rat dorsal horn neurones. 1987

R J Knox, and A H Dickenson

We have studied the effects of 3 putative kappa-opioid receptor agonists, U50488H, ethylketocyclazocine (EKC) and dynorphin A1-13 (DYN) on the processing of nociceptive information in the dorsal horn of the rat under halothane anaesthesia. Extracellular single unit recordings were made from convergent or multireceptive lumbar dorsal horn neurones, which could be excited by impulses in A beta and C fibre afferents following transcutaneous electrical stimulation of their ipsilateral hind paw receptive fields and also by noxious and innocuous natural stimuli. Agonists were applied directly onto the surface of the spinal cord. DYN and U50488H consistently produced both a facilitation and inhibition of the C-fibre evoked nociceptive responses of individual cells, these dual effects being relatively insensitive to naloxone antagonism and cancelled each other for the whole population of cells. A beta fibre-evoked responses were little altered. In contrast, EKC consistently depressed C-fibre transmission in a dose-dependent, naloxone reversible manner, analogous to, but considerably less potent than intrathecal morphine under identical experimental conditions. Agonist-induced effects on neuronal responses to natural stimulation (noxious pinch and innocuous prod) were consistent with the changes observed with the electrically evoked responses. The present results therefore indicate that EKC probably exerts its spinal antinociceptive activity in the rat spinal cord in a manner akin to mu-receptor activation. Results with U50488H and DYN indicate that -opioids can excite and inhibit individual neurones but produce no overall change on the whole population, so differing from effects mediated by the other opiate receptors.

UI MeSH Term Description Entries
D007278 Injections, Spinal Introduction of therapeutic agents into the spinal region using a needle and syringe. Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008297 Male Males
D009270 Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. MRZ 2593-Br,MRZ-2593,Nalone,Naloxon Curamed,Naloxon-Ratiopharm,Naloxone Abello,Naloxone Hydrobromide,Naloxone Hydrochloride,Naloxone Hydrochloride Dihydride,Naloxone Hydrochloride, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Naloxone, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Narcan,Narcanti,Abello, Naloxone,Curamed, Naloxon,Dihydride, Naloxone Hydrochloride,Hydrobromide, Naloxone,Hydrochloride Dihydride, Naloxone,Hydrochloride, Naloxone,MRZ 2593,MRZ 2593 Br,MRZ 2593Br,MRZ2593,Naloxon Ratiopharm
D009412 Nerve Fibers Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM. Cerebellar Mossy Fibers,Mossy Fibers, Cerebellar,Cerebellar Mossy Fiber,Mossy Fiber, Cerebellar,Nerve Fiber
D010146 Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D003496 Cyclazocine An analgesic with mixed narcotic agonist-antagonist properties.

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