Spinal mu-, delta- and kappa-opioid receptors mediate intense stimulation-elicited inhibition of a nociceptive reflex in the rat.
Intense electrical stimulation of meridian points in the rat inhibits the nociceptive tail withdrawal reflex. The objective of the present study was to determine whether spinal opioid receptors mediate this inhibition. Electrical stimulation was applied with 2 ms square pulses, at 4 Hz for 20 min at 20 times the threshold, to previously defined meridian points in the hindlimb. Threshold was the minimum current required to elicit muscle twitch. In lightly anaesthetized intact rats (n = 8) stimulation inhibited tail withdrawal during and for greater than one hour after the end of stimulation. In unanaesthetized spinal rats (n = 12) this inhibition was less and the post-stimulation effect lasted for 15 min. In control anaesthetized intact (n = 28) and unanaesthetized spinal rats (n = 14) placement of electrodes without stimulation had no effect. In spinal rats, preadministration of naloxone (25 mg/kg, i.p.) blocked the evoked inhibition (n = 11). In intact animals both naloxone (n = 8) and the mu-opioid receptor antagonist, beta-funaltrexamine (10 nmol; n = 9), given via a chronic intrathecal catheter, attenuated inhibitions during and after the end of stimulation by 50-60%. The delta-opioid receptor antagonist H-Tyr-tic psi[CH2NH]Phe-Phe-OH (TIPP[psi]; 10 nmol; n = 7) and the kappa-opioid receptor antagonist nor-binaltorphimine (10 nmol; n = 13) given by lumbar puncture attenuated the inhibition during the stimulation by 30% and 56%, respectively; both antagonists blocked the post-stimulation effect and even facilitated the withdrawal. The data suggest that spinal mu-, delta- and kappa-opioid receptors each contribute to the evoked inhibition.
Romita
V V
VV
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Henry
J L
JL
D000818:Animals; D004558:Electric Stimulation; D007278:Injections, Spinal; D008297:Male; D016740:Meridians; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000502:physiology; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu