A pharmacological study of the modulation of neuronal and behavioural nociceptive responses in the rat trigeminal region.
Electrical stimulation of the brain, particularly in the periventricular grey areas, caused long-lasting increases in behavioural escape thresholds to heating and mechanical stimuli applied to the facial region of the rat. The brain stimulation selectively suppressed responses to noxious stimuli. Responses to non-noxious stimuli, evoked by low threshold brush, were unaffected. The same animals that were studied in the behavioural tests were then anaesthetized with urethane and the inhibitory effect of the same brain stimulation was studied in single neurones recorded in the caudal trigeminal nucleus. A clear correlation (rs = 0.63) emerged between degree of behavioural antinociception and the amount of inhibition seen in nociceptive neurones. In addition the mean duration of the inhibition (6 min) was similar to the mean duration of the antinociceptive effect (7.3 min). Other classes of non-nociceptive neurones were unaffected by the stimulation. The neurones were also studied using iontophoretically applied monoamine candidates for the inhibitory neurotransmitter noradrenaline (NA) and 5-hydroxytryptamine (5-HT). The profile of the effects of NA most closely fitted that of the inhibitory neurotransmitter. This profile was expressed in terms of depression and excitation of different classes of neurones, and by the duration of effects. The depressants effects could be antagonized by iontophoretic idazoxan. In addition clonidine induced long-lasting depression of firing. 5-HT was more likely than NA to excite nociceptive neurones and to depress non-nociceptive neurons. Only NA consistently elevated thermal response thresholds in a similar manner to that produced by brain stimulation. These results provide some support for the hypothesis that selective descending inhibition of nociceptive responses in neurones of the rat caudal trigeminal nucleus is mediated by NA, possibly by an action at alpha2-adrenoceptors.
Cahusac
P M
PM
Department of Pharmacology, Medical School, University Walk, Bristol, UK.
Morris
R
R
Hill
R G
RG
D000818:Animals; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects*; D006358:Hot Temperature; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D013314:Stress, Mechanical; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects*
D012701:Serotonin; D009638:Norepinephrine