Selective modulation of tonic aversive qualities of neuropathic pain by morphine in the central nucleus of the amygdala requires endogenous opioid signaling in the anterior cingulate cortex. Issue 3 (March 2020)

• Record Type: Journal Article
• Authors: Navratilova, Edita; Nation, Kelsey; Remeniuk, Bethany; Neugebauer, Volker; Bannister, Kirsty; Dickenson, Anthony H.; Porreca, Frank
• Is Part Of: Pain. Volume 161:Issue 3(2020)
• Publication Date: 2020-03
• Subjects: Amygdala -- Opioid -- Morphine -- Anterior cingulate cortex -- Diffuse noxious inhibitory controls -- Conditioned place preference -- Affective aspects of pain; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001748
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: The amygdala is a key subcortical region believed to contribute to emotional components of pain. As opioid receptors are found in both the central (CeA) and basolateral (BLA) nuclei of the amygdala, we investigated the effects of morphine microinjection on evoked pain responses, pain-motivated behaviors, dopamine release in the nucleus accumbens (NAc), and descending modulation in rats with left-side spinal nerve ligation (SNL). Morphine administered into the right or left CeA had no effect on nerve injury–induced tactile allodynia or mechanical hyperalgesia. Right, but not left, CeA morphine produced conditioned place preference (CPP) and increased extracellular dopamine in the NAc selectively in SNL rats, suggesting relief of aversive qualities of ongoing pain. In SNL rats, CPP and NAc dopamine release following right CeA morphine was abolished by blocking mu opioid receptor signaling in the rostral anterior cingulate cortex (rACC). Right CeA morphine also significantly restored SNL-induced loss of the diffuse noxious inhibitory controls, a spino-bulbo-spinal pain modulatory mechanism, termed conditioned pain modulation in humans. Microinjection of morphine into the BLA had no effects on evoked behaviors and did not produce CPP in nerve-injured rats. These findings demonstrate that the amygdalar action of morphine is specific to the right CeA contralateral to the side of injury and results in enhancement of net descending inhibition. In addition, engagement of mu opioid receptors in the right CeA modulates affective qualities of ongoing pain through endogenous opioid neurotransmission within the rACC, revealing opioid-dependent functional connections from the CeA to the rACC. Abstract : Opioids in the right central amygdala nucleus contralateral to neuropathic injury restore diffuse noxious inhibitory controls in rats with nerve ligation and relieve aversive qualities of ongoing pain.