Acúfenos: Sección mecanismos fisopatológicos

Nucleus accumbens facilitates nociception

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Robert W. Gear^{a, c} and Jon D. Levine^{a, b, c, ,}

^a Department of Oral and Maxillofacial Surgery, University of California, San Francisco 94143–0440
^b Department of Medicine, University of California, San Francisco 94143–0440
^c Department of Division of Neuroscience, University of California, San Francisco 94143–0440

Received 23 January 2011; 

revised 16 March 2011; 

accepted 24 March 2011. 

Available online 31 March 2011.

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-Ala², N-Me-Phe⁴,Gly⁵-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 Cys²,Tyr³, Orn⁵,Pen⁷amide (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.

Research Highlights

►Spinal intrathecally administered DAMGO induces hetersegmental antinociception. ►Opioid receptors in nucleus accumbens mediate this effect. ►Intra-accumbens lidocaine attenuates nociceptive responses. ►Intra-accumbens kainate facilitates nociceptive responses. ►Nucleus accumbens may be important in controlling pain sensitivity.

Keywords: rat; pain; analgesia; opioids; mu; delta; lidocaine; glutamate; kainate; jaw opening reflex

Abbreviations: ANOVA, analysis of variance; CTOP, Cys²,Tyr³,Orn⁵,Pen⁷amide; DAMGO, [D-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin; DPDPE, D-Pen^2,5-enkephalin; EMG, electromyographic; GABA, gamma amino butyric acid; i.t., intrathecal; JOR, jaw opening reflex; NAc, nucleus accumbens; QX-314, lidocaine N-ethyl bromide salt; RVM, rostral ventral medulla

Corresponding author at: Dept. of Oral & Maxillofacial Surgery, 521 Parnassus Ave, Rm C522, Campus Box 0440, University of California, San Francisco, San Francisco, CA 94143–0440. Fax: + 1 415 476 6305. 

fuente Experimental Neurology