title: Nucleus accumbens facilitates nociception.
abstract: We have previously demonstrated an opioid link in nucleus accumbens (NAc) that mediates antinociception produced by a novel ascending pain modulation pathway. For example, noxious stimulation induces heterosegmental antinociception that is mediated by both mu- and delta-opioid receptors in NAc. However, spinal intrathecal administration of the mu-receptor agonist [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) also induces heterosegmental antinociception. The aim of the present study in the rat was to identify the intra-NAc opioid receptors that mediate the antinociceptive effects of spinally administered DAMGO and also to determine the effect of NAc efferent activity on nociception. Intra-NAc administration of either the mu-opioid receptor antagonist Cys(2),Tyr(3), Orn(5),Pen(7)amide (CTOP) or the delta-opioid receptor antagonist naltrindole blocked the antinociceptive effect of spinally administered DAMGO on the jaw-opening reflex (JOR). Injection of quaternary lidocaine (QX-314) attenuated the JOR, suggesting that the output of NAc is pronociceptive. In support of this, intra-NAc injection of the excitatory amino acid agonist kainate enhanced the JOR. Thus, it is possible to modulate activity in NAc to bidirectionally attenuate or enhance nociception, suggesting a potential role for NAc in setting nociceptive sensitivity.
authors: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, CA 94143-0440, USA.
authors: Robert W
authors: RW
authors: Gear
authors: Jon D
authors: JD
authors: Levine
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004567:Electrodes, Implanted; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology / Q000627:therapeutic use; D007278:Injections, Spinal; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009271:Naltrexone; D008012:Lidocaine; C055382:naltrindole