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1.
J Pain. 2014 Dec;15(12):1305-18. doi: 10.1016/j.jpain.2014.09.007. Epub 2014 Sep 23.

N-methyl-D-aspartate receptor agonism and antagonism within the amygdaloid central nucleus suppresses pain affect: differential contribution of the ventrolateral periaqueductal gray.

Author information

1
Department of Psychology, Behavioral & Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan.
2
Department of Psychology, Behavioral & Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan. Electronic address: borszcz@wayne.edu.

Abstract

The amygdala contributes to the generation of pain affect, and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study compared the contribution of N-methyl-d-aspartate (NMDA) receptor agonism and antagonism in the CeA to generation of the affective response of rats to an acute noxious stimulus. Vocalizations that occur following a brief tail shock (vocalization afterdischarges) are a validated rodent model of pain affect and were preferentially suppressed, in a dose-dependent manner, by bilateral injection into the CeA of NMDA (.1, .25, .5, or 1 μg/side) or the NMDA receptor antagonist d-(-)-2-amino-5-phosphopentanoic acid (AP5; 1, 2, or 4 μg/side). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of NMDA or AP5 into the CeA. Injection of NMDA, but not AP5, into the CeA increased c-Fos immunoreactivity in the ventrolateral periaqueductal gray, and unilateral injection of the μ-opiate receptor antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; .25 μg) into ventrolateral periaqueductal gray prevented the antinociception generated by injection of NMDA into the CeA. These findings demonstrate that although NMDA receptor agonism and antagonism in the CeA produce similar suppression of pain behaviors, they do so via different neurobiologic mechanisms.

PERSPECTIVE:

The amygdala contributes to production of the emotional dimension of pain. NMDA receptor agonism and antagonism within the CeA suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders.

KEYWORDS:

NMDA; Nociception; amygdala; c-Fos; emotion; glutamate; periaqueductal gray; vocalization

PMID:
25261341
PMCID:
PMC4353604
DOI:
10.1016/j.jpain.2014.09.007
[Indexed for MEDLINE]
Free PMC Article
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2.
Neuroscience. 2014 Mar 28;263:72-87. doi: 10.1016/j.neuroscience.2014.01.009. Epub 2014 Jan 13.

Separating analgesia from reward within the ventral tegmental area.

Author information

1
Behavioral and Cognitive Neuroscience Program, Department of Psychology, Wayne State University, Detroit, MI 48202, USA.
2
Behavioral and Cognitive Neuroscience Program, Department of Psychology, Wayne State University, Detroit, MI 48202, USA. Electronic address: borszcz@wayne.edu.

Abstract

Activation of the dopaminergic mesolimbic reward circuit that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress emotional responses to noxious stimuli, and presumably contributes to the addictive liability of strong analgesics. VTA dopamine neurons are activated via cholinergic afferents and microinjection of carbachol (cholinergic agonist) into VTA is rewarding. Here, we evaluated regional differences within VTA in the capacity of carbachol to suppress rats' affective response to pain (vocalization afterdischarges, VADs) and to support conditioned place preference (CPP) learning. As carbachol is a non-specific agonist, muscarinic and nicotinic receptor involvement was assessed by administering atropine (muscarinic antagonist) and mecamylamine (nicotinic antagonist) into VTA prior to carbachol treatment. Unilateral injections of carbachol (4μg) into anterior VTA (aVTA) and posterior VTA (pVTA) suppressed VADs and supported CPP; whereas, injections into midVTA failed to effect either VADs or CPP. These findings corroborate the hypothesis that the neural substrates underlying affective analgesia and reward overlap. However, the extent of the overlap was only partial. Whereas both nicotinic and muscarinic receptors contributed to carbachol-induced affective analgesia in aVTA, only muscarinic receptors mediated the analgesic action of carbachol in pVTA. The rewarding effects of carbachol are mediated by the activation of both nicotinic and muscarinic receptors in both aVTA and pVTA. The results indicate that analgesia and reward are mediated by separate cholinergic mechanisms within pVTA. Nicotinic receptor antagonism within pVTA failed to attenuate carbachol-induced analgesia, but prevented carbachol-induced reward. As addictive liability of analgesics stem from their rewarding properties, the present findings suggest that these processes can be neuropharmacologically separated within pVTA.

KEYWORDS:

addiction; analgesia; muscarinic; nicotinic; pain; reward

[Indexed for MEDLINE]
Free PMC Article
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