title: DAMGO in the central amygdala alleviates the affective dimension of pain in a rat model of inflammatory hyperalgesia.
abstract: Pain has sensory-discriminative and emotional-affective dimensions. Recent studies show that the affective component can be assessed with a conditioned place avoidance (CPA) test. We hypothesized that systemic morphine before a post-conditioning test would more potently attenuate the affective aspect compared to the sensory component and that [d-Ala2-N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO), a μ-selective opioid receptor agonist, injected into the central nucleus of the amygdala (CeA) would reduce established CPA. A rat model of inflammatory pain, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a CPA test. Three experiments were performed on adult male Sprague-Dawley rats. Systemic morphine (0.5 or 1.0mg/kg) in Experiment 1, intrathecal (i.t.) morphine (2.5 μg/rat) in Experiment 2, and intra-CeA DAMGO (7.7-15.4 ng/0.4 μl) in Experiment 3 were given to CFA-injected rats (n=6-8/group) prior to a post-conditioning test. Saline-injected rats were used as control. Time spent in a pain-paired compartment was recorded twice, before conditioning and after a post-conditioning test. Paw withdrawal latency (PWL) to a noxious thermal stimulus was measured before experiment at day-1 and after the post-conditioning test; hyperalgesia was defined as a decrease in PWL. The data showed that CFA-injected rats had significantly negative CPA compared to those of saline-injected rats (P<0.05). Low-dosage systemic morphine significantly (P<0.05) reduced CFA-induced CPA but had no effect on PWL. I.t. morphine did not inhibit the display of CPA but significantly increased PWL, suppressing hyperalgesia (P<0.05). Intra-CeA DAMGO significantly inhibited the display of CPA compared to saline (P<0.05) but had no effect on PWL. The data demonstrate that morphine attenuates the affective component more powerfully than it does the sensory and suggests that the sensory and the emotional-affective dimensions are underpinned by different mechanisms.
authors.affiliation: Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA. Electronic address: Rzhan001@umaryland.edu.
authors.forename: R-X
authors.initials: RX
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Pan
authors.forename: B M
authors.initials: BM
authors.lastname: Berman
authors.forename: K
authors.initials: K
authors.lastname: Ren
authors.forename: L
authors.initials: L
authors.lastname: Lao
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine
keywords: BLA; CFA; CPA; CeA; DAMGO; IACUC; Institutional Animal Care and Use Committee; N-methyl-d-aspartate; NMDA; PWL; [d-Ala2-N-Me-Phe4, Gly-ol5]-enkephalin; amygdala; basolateral amygdaloid nucleus; central nucleus of the amygdala; complete Freund adjuvant; conditioned place avoidance; hyperalgesia; opioid; pain; paw withdrawal latency; spinal cord