Pharmacological and Electrophysiological Studies of Morphine and Enkephalin on Rat Supraspinal Neurones and Cat Spinal Neurones

Abstract

1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone. 2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed. 3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone. 4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine. 5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect. 6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.

Blockade of Striatal Neurone Responses to Morphine by Aminophylline: Evidence for Adenosine Mediation of Opiate Action

“…The poor responses obtained in the cortex are consistent with the low density of opiate receptors found in this area (Pert, Kuhar & Snyder, 1975;Pert et al, 1976) although again there is no agreement as to whether inhibition (Satoh, Zieglgansberger & Herz, 1975;Zieglgansberger & Fry, 1976) or excitation (Davies & Dray, 1978) predominates; our results favour the former workers.…”

“…In the brain stem both predominantly excitatory (Bradley & Dray, 1974;Bradley et al, 1976b;Davies & Dray, 1978) and predominantly inhibitory (Gent & Wolstencroft, 1976a, b;Gent, Smyth, Snell & Wolstencroft, 1977) effects have been observed as well as some, rare, biphasic responses (Gent & Wolstencroft, 1976b;Bradley et al, 1976a, b). More anteriorly, in the striatum, inhibition of neuronal firing appears to be the predominant morphine response (Zieglgansberger & Fry, 1976;Dafny et al, 1979) and the results presented here agree with those observations.…”

Actions of opioids on primate spinothalamic tract neurons

“…Furthermore, when NLX was applied with a large iontophoretic current, the drug generally produced actions of its own, often of the same kind as produced by the opioid substance being tested (cf: Gruol et al, 1980). The observations of others support the idea that the antagonistic effects of naloxone are probably better demonstrated by systemic than by iontophoretic administration (Calvillo et al, 1974(Calvillo et al, , 1979Davies and Dray, 1978).…”

“…Several alternative hypotheses have been used to explain the variable effects of opioid substances on dorsal horn neurons. These have included differential effects on non-nociceptive versus nociceptive cells (Belcher and Ryall, 1978;Calvillo et al, 1974Calvillo et al, , 1979Einspahr and Piercey, 1980;Le Bars et al, 1975); contrary actions on cells lying in different laminae (Juma and Grossman, 1976;Sastry and Goh, 1983;Woolf and Fitzgerald, 198 1); control of nociceptive cells located deeper in the dorsal horn by opiate actions on dendrites or on other neurons located more superficially (Davies and Dray, 1978;Duggan et al, 1977a, b, 198 1;Sastry and Goh, 1983;Woolf and Fitzgerald, 1981); blockade of receptors mediating excitatory or inhibitory actions of other neurotransmitters Pomeranz, 1973, 1976); and toxic effects related to high concentrations of drugs emitted from iontophoretic electrodes . We did not note any differences in opiate effects on STT cells at various depths in the dorsal horn, nor were there any obvious differences in the responses of LT, WDR, or HT STT cells.…”

“…be inhibitory or excitatory, although the usual effect is inhibition (Davies and Dray, 1978;Duggan et al, 1977bDuggan et al, , 1981RandiC and MiletiC, 1978;Sastry and Goh, 1983;Satoh et al, 1979;Zieglgtinsberger and Sutor, 1983;Zieglgansberger and Tulloch, 1979).…”