Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias

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The present experiments were undertaken to assess the role of neurons in the nucleus raphe nagnus (NRM) in mediating opiate and stimulation-produced analgesias. A cannode for both electrical stimulation and local opiate microinjection was placed in the midbrain periaqueductal gray region of decerebrate or chloralose-urethane anesthetized cats. Microelectrodes recorded the responses of medullary NRM neurons. Raphe-spinal neurons were identified by antidromic activation from the cervical spinal cord.

Fifteen of 20 raphe-spinal cells tested were excited by electrical stimulation of the midbrain.

Of 49 NRM neurons tested, 26 were excited by either systemic or midbrain injection of opiate agonist. Twelve of 33 NRM cells tested by midbrain microinjection were excited. In 10 the effect was reversed by naloxone. Seventeen raphe-spinal neurons were tested; 5 showed naloxone-reversible excitation to either midbrain or intravenous injection of opiates. NRM neurons respond to auditory and somatic stimuli; at least half respond maximally to somatic stimuli of noxious intensity.

These findings are consistent with the hypothesis that the raphe-spinal projection mediates opiate and electrical stimulation-produced effects from midbrain sites. The properties of raphe-spinal neurons suggest that they are part of a negative feedback system which monitors and limits the output of spinal dorsal horn pain-transmission neurons.

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