Intracerebroventricular morphine decreases descending inhibitions acting on lumbar dorsal horn neuronal activities related to pain in the rat.
Recordings were made from convergent neurons in the lumbar dorsal horn of the rat. These neurons were activated by both innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold 2-msec square-wave pulses to the center of the receptive field resulted in responses to A- and C-fiber activation being observed: 27.2 +/- 2.2 (mean +/- S.E.M.) C-fiber latency spikes were evoked per stimulus. This type of response was inhibited by applying noxious conditioning stimuli to heterotopic areas of the body; in particular, immersing the tail in a 52 degrees C waterbath caused a 74.2 +/- 2.0% inhibition of the C-fiber evoked responses; such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects of microinjections of morphine (0.6-40 micrograms; 2 microliter) within the 3rd ventricle on both the unconditioned C-fiber-evoked responses and the inhibitory processes triggered from the tail were investigated in an attempt to answer two questions: 1) does i.c.v. morphine increase tonic descending inhibitory processes? and 2) what are the effects of i.c.v. morphine on descending inhibitory processes triggered phasically by noxious stimuli? The predominant effect of i.c.v. morphine on the C-fiber-evoked responses was a facilitation (17 of 26 cases). Such a facilitation was dose-related in the 0.6 to 40 microgram range and naloxone reversible; it plateaued from 20 min after the microinjection. No clear relationship was found between the number of C-fiber evoked responses in the control sequences and the subsequent effect of i.c.v. morphine. Intracerebroventricular morphine clearly reduced DNIC in the majority of cases (21 of 26). Such a reduction was dose-related in the 0.6 to 2.5 microgram range and naloxone reversible; it plateaued within 90 min of microinjection. No clear relationship was found between the changes in DNIC and either the number of C-fiber-evoked spikes in the control sequences or the changes in the C-fiber responses induced by i.c.v. morphine. Autoradiographic controls using [3H]morphine showed a labeling along the ventricle wall including the hypothalamus, the periaqueductal gray matter and the floor of the 4th ventricle, three regions which have been implicated in the control of nociceptive transmission at the spinal level. Diffusion from the ventricle wall was over a distance of 0.5 mm and was identical whether observed 20 or 95 min after the microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)
Bouhassira
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Unité de Recherches de Neurophysiologie Pharmacologique, Institut National de la Santé et de la Recherche Médicale (U161), Paris, France.
Villanueva
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Le Bars
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D000818:Animals; D001345:Autoradiography; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009412:Nerve Fibers / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000502:physiology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D009020:Morphine