Pain-related cortico-limbic plasticity and opioid signaling. (15th June 2023)

• Record Type: Journal Article
• Authors: Neugebauer, Volker; Presto, Peyton; Yakhnitsa, Vadim; Antenucci, Nico; Mendoza, Brianna; Ji, Guangchen
• Is Part Of: Neuropharmacology. Volume 231(2023)
• Publication Date: 2023-06-15
• Subjects: Amygdala -- Prefrontal cortex -- Mesolimbic -- Neuroplasticity -- Pain -- Kappa opioid receptor -- Mu opioid receptor -- Delta opioid receptor; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2023.109510
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Neuroplasticity in cortico-limbic circuits has been implicated in pain persistence and pain modulation in clinical and preclinical studies. The amygdala has emerged as a key player in the emotional-affective dimension of pain and pain modulation. Reciprocal interactions with medial prefrontal cortical regions undergo changes in pain conditions. Other limbic and paralimbic regions have been implicated in pain modulation as well. The cortico-limbic system is rich in opioids and opioid receptors. Preclinical evidence for their pain modulatory effects in different regions of this highly interactive system, potentially opposing functions of different opioid receptors, and knowledge gaps will be described here. There is little information about cell type- and circuit-specific functions of opioid receptor subtypes related to pain processing and pain-related plasticity in the cortico-limbic system. The important role of anterior cingulate cortex (ACC) and amygdala in MOR-dependent analgesia is most well-established, and MOR actions in the mesolimbic system appear to be similar but remain to be determined in mPFC regions other than ACC. Evidence also suggests that KOR signaling generally serves opposing functions whereas DOR signaling in the ACC has similar, if not synergistic effects, to MOR. A unifying picture of pain-related neuronal mechanisms of opioid signaling in different elements of the cortico-limbic circuitry has yet to emerge. This article is part of the Special Issue on "Opioid-induced changes in addiction and pain circuits". Highlights: Preclinical data suggest varied opioid effects on pain across cortico-limbic regions. Opioid receptor subtype functions in cortico-limbic circuits need clarification. MOR-dependent analgesia relies on ACC and amygdala with some mesolimbic involvement. KOR signaling generally serves opposing functions to MOR. DOR signaling often has similar, if not synergistic effects, to MOR.