Delta-opioid mediated inhibitions of acute and prolonged noxious-evoked responses in rat dorsal horn neurones.
1. The effects of a selective delta-opioid agonist Tyr-D-Ser(Otbu)-Gly-Phe-Leu-Thr (DSTBULET) were examined on the C- and A beta-evoked responses of convergent dorsal horn neurones in the halothane anaesthetized, intact rat. 2. Intrathecal DSTBULET produced selective dose-dependent inhibitions of electrically-evoked C fibre responses of both superficial and deep neurones. A near-complete inhibition of 83 +/- 5% followed 100 micrograms of DSTBULET and the ED50 was 9 micrograms (13.5 nmol). Inhibitions were antagonised by intrathecal naloxone and ICI 174,864 but were not antagonised by pretreatment with intrathecal beta-funaltrexamine at a dose that blocked mu-opioid effects. By contrast, DSTBULET produced excitations of electrically-evoked responses of cells recorded in a zone intermediate between the superficial and deep neurones. 3. DSTBULET (50 micrograms) was also tested on the more prolonged noxious neuronal response produced by subcutaneous formalin (5%, 50 microliters) into the receptive field. DSTBULET profoundly inhibited the response to formalin. Pretreatment with ICI 174,864 before DSTBULET antagonised the effects of the delta-agonist on the formalin response. 4. The full peptidase inhibitor kelatorphan, known to protect endogenous enkephalins, was also tested on the formalin response. The intrathecal administration of 50 micrograms kelatorphan has previously been shown to inhibit electrically-evoked C fibre resonses of dorsal horn neurones and to be antagonised by ICI 174,864. The same dose of kelatorphan inhibited the formalin response in the present study. 5. From this study it appears that the delta-opioid agonist DSTBULET can produce profound inhibitions of the responses of convergent neurones to nociceptive afferent inputs. Furthermore, activation of delta-opioid receptors either by DSTBULET, or by protection of endogenous enkephalins with kelatorphan, can inhibit a more prolonged chemically-evoked nociceptive input onto these dorsal horn neurones.
Sullivan
A F
AF
Department of Pharmacology, University College London.
Dickenson
A H
AH
Roques
B P
BP
D000818:Animals; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta
D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine