Pain
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The endogenous cannabinoid (endocannabinoid) system plays an important role in fear-conditioned analgesia (FCA) and expression and extinction of conditioned fear. The hippocampus has an established role in both pain and conditioned fear and is a substrate for endocannabinoid activity. This study aimed to investigate the role of the endocannabinoid system in the ventral hippocampus (vHip) in FCA and in fear responding in the presence of nociceptive tone. ⋯ The URB597-induced enhancement of FCA was blocked by intra-vHip administration of the cannabinoid(1) (CB(1)) receptor antagonist/inverse agonist rimonabant. Intra-vHip rimonabant alone had no effect on the expression of FCA, and URB597 did not significantly alter formalin-evoked nociceptive behaviour in non-fear-conditioned rats. These data suggest an important role for the endocannabinoid system in the vHip in FCA, whereby levels of 2-arachidonoylglycerol and the FAAH substrates palmitoylethanolamide and anandamide are increased in rats expressing FCA, and pharmacological inhibition of FAAH in the vHip enhances this form of endogenous analgesia via a CB(1) receptor-dependent mechanism.
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Randomized Controlled Trial Multicenter Study
Chronic postsurgical pain after nitrous oxide anesthesia.
Nitrous oxide is an antagonist at the N-methyl-D-aspartate receptor and may prevent the development of chronic postsurgical pain. We conducted a follow-up study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial patients to evaluate the preventive analgesic efficacy of nitrous oxide after major surgery. The ENIGMA trial was a randomized controlled trial of nitrous oxide-based or nitrous oxide-free general anesthesia in patients presenting for noncardiac surgery lasting more than 2 hours. ⋯ In addition, severe pain in the first postoperative week, wound complication, and abdominal incision increased the risk of chronic pain. In conclusion, chronic postsurgical pain was common after major surgery in the ENIGMA trial. Intraoperative nitrous oxide administration was associated with a reduced risk of chronic postsurgical pain.