A single restraint stress exposure potentiates analgesia induced by intrathecally administered DAGO.
In rats, restraint exposure potentiates the magnitude and duration of analgesia following both the peripheral and intracerebroventricular administration of several opioid agonists as compared to non-stressed controls. It has been suggested that the site of action whereby restraint leads to potentiated opioid analgesia is located supraspinally. However, the possible contribution of spinal analgesic mechanisms also warrants investigation. Thus, the purpose of the present study was two-fold: (1) to determine whether a single exposure to restraint stress would result in the dose-dependent potentiation of analgesia following the intrathecal (i.t.) administration of the mu (mu)-receptor selective opioid agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) and (2) to quantify the degree of analgesia in restrained vs. non-restrained rats using the tail-flick and hot-plate analgesic assays. Using rats implanted with chronic i.t. cannula, dose- and time-course curves were observed following the i.t. administration of DAGO. The results demonstrate that both the duration and magnitude of analgesia was significantly potentiated in restrained rats compared to non-restrained controls. Restraint-treated rats receiving 0.15-0.6 micrograms of DAGO i.t. showed 1.3-1.5-fold potentiation of analgesia in the tail-flick assay and a 2.3-5.6-fold potentiation using the hot-plate assay. Restraint immobilization potentiated the magnitude and duration of DAGO-induced analgesia administered by the i.t. route as measured by the tail-flick and hot-plate assays. These data suggest that spinal analgesic mechanisms significantly contribute to the enhanced analgesic potency of opioids in subjects exposed to restraint stress.
Calcagnetti
D J
DJ
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-9989.
Stafinsky
J L
JL
Crisp
T
T
D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004357:Drug Synergism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*
D000700:Analgesics; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-