Characterization of coeruleospinal inhibition of the nociceptive tail-flick reflex in the rat: mediation by spinal alpha 2-adrenoceptors.
Several lines of evidence implicate bulbospinal noradrenergic pathways in antinociception and descending inhibition. In the present study, descending inhibition of the nociceptive tail-flick (TF) reflex by electrical stimulation in the dorsolateral pons (DLP) and the spinal neurotransmitter(s) mediating that inhibition were characterized in lightly pentobarbital-anesthetized rats. It was determined that 10 s of stimulation in the DLP prior to the application of heat to the tail resulted in optimum (lowest) thresholds for inhibition of the TF reflex. Conditioning-test studies indicated that the duration of the inhibitory effects produced by stimulation outlasted the 10-s period of stimulation by approximately 5 s. Systematic mapping studies revealed that inhibition of the TF reflex could be produced by stimulation throughout a large portion of the DLP; however, stimulation sites requiring the lowest intensities of stimulation (less than or equal to 25 microA) were in the locus coeruleus/subcoeruleus. Changes in blood pressure were not produced at this intensity and duration of stimulation. S-glutamate microinjections and stimulation strength-duration determinations suggest that inhibition of the TF reflex produced by stimulation in the locus coeruleus/subcoeruleus results from activation of cell bodies. The intrathecal administration of pharmacologic antagonists (phentolamine, yohimbine, prazosin, naloxone, methysergide, atropine and bicuculline) revealed that only the alpha-adrenergic antagonists phentolamine and yohimbine resulted in significant increases in stimulation thresholds in the locus coeruleus/subcoeruleus for inhibition of the TF reflex (83.1 and 93.9%, respectively). These results indicate that inhibition of the spinal nociceptive TF reflex produced by electrical stimulation in the locus coeruleus/subcoeruleus is at least in part a noradrenergic, postsynaptic alpha 2-adrenoceptor-mediated effect.
Jones
S L
SL
Gebhart
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GF
D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D004525:Efferent Pathways / Q000503:physiopathology; D005971:Glutamates; D018698:Glutamic Acid; D008125:Locus Coeruleus / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D011149:Pons / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology*
D005971:Glutamates; D011942:Receptors, Adrenergic, alpha; D018698:Glutamic Acid