Morphine does not antagonize the substance P mediated excitation of dorsal horn neurons.
Multibarrelled microelectrodes were used to test the effects of iontophoretically released substance P (SP), morphine, glutamate, and naloxone on spinal cord dorsal horn neurons. Cells excited by SP were also excited by noxious stimuli, a finding consistent with the hypothesis that SP is the neurotransmitter released by primary nociceptor afferents to excite dorsal horn neurons. Iontophoretic morphine failed to depress the SP-induced discharges. Indeed, iontophoretic morphine frequently potentiated the SP responses. In addition to potentiating SP-induced discharges, iontophoretic morphine frequently increased both the spontaneous activity of dorsal horn neurons and the activity evoked in these cells by noxious cutaneous heat and iontophoretic glutamate. Naloxone did not antagonize these excitatory effects. Intravenous morphine only depressed spontaneous discharges. Nevertheless, iontophoretic morphine still produced excitatory effects in spinal animals pretreated with analgesic doses of intravenous morphine. It is concluded that such excitatory effects are toxic actions indicative of supratherapeutic morphine concentrations in the vicinity of the neuron being studied. Intravenously administered morphine depressed the spontaneous activity of dorsal horn neurons of spinal cats, but failed to depress their responses to SP. Morphine also failed to antagonize SP's biological effects in peripheral systems (contraction of isolated guinea pig ileum, rabbit hypotensive effect, rat sialogogic response). It is concluded that morphine is not a substance P receptor antagonist. The results are discussed with respect to the hypotheses that (1) the spinal analgesic effects of systemically administered morphine occur on presynaptic terminals of sensory neurons, and (2) an SP antagonist might be a unique analgesic agent.
D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D012701:Serotonin; D013373:Substance P; D009020:Morphine