Pain‐induced alterations in the dynorphinergic system within the mesocorticolimbic pathway: Implication for alcohol addiction

Abstract

The International Association for the Study of Pain (IASP) defines pain "as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" (IASP Task Force on Taxonomy, 1994). As an emotional experience, pain usually negatively impacts patients' daily lives, not only because of physical impairment but also because of the appearance of neuropsychiatric comorbidities such as depression, anxiety, or even addiction. Because of this complex situation, treating pain and its associated neuropsychiatric pathologies becomes a difficult task for the health-care personnel.Pain and reward are opposed responses processed by interconnected brain areas that keep an adequate cognitive and emotional function (i.e., anterior cingulate cortex, dorsal striatum, and amygdala). Furthermore, pain can modify reward processing by decreasing dopamine (DA) release in nucleus accumbens (NAc), which leads to anhedonia or a negative affect state (Elman, Borsook, & Volkow, 2013;Massaly et al., 2019). Thereby, pain can be an important factor affecting addiction, especially in people with a previous history of drug abuse. In fact, inflammatory pain produces mu opioid receptor (MOR) desensitization and/or a reduction in its levels in the mesocorticolimbic system (MCLS;Ozaki et al., 2002;Zubieta et al., 2001). Interestingly, rats presenting inflammatory pain needed higher doses of heroin to

Sex-dependent effect of inflammatory pain on negative affective states is prevented by kappa opioid receptors blockade in the nucleus accumbens shell

“…Moreover, the MCLS seems to be involved in the modulation of negative affective states occurring in pain conditions. (Caputi et al, 2019;Jesús David Lorente et al, 2020;Massaly et al, 2019) Thereby, we measured the mRNA levels of pDYN and KOR in the NAc and the Amy by qRT-PCR together with its protein expression in these areas by ELISA and western blot.…”

“…Many studies highlighted that pain induces anxiety-and anhedonia-like behaviours as well as low motivation for natural reinforcement under a goal-directed behaviour (Lorente et al, 2020;Markovic et al, 2021;Massaly et al, 2019). However, unfortunately, most of these studies used only male subjects and limited observations only to specific time points after pain induction.…”

Crosstalk between Mu-Opioid receptors and neuroinflammation: Consequences for drug addiction and pain

“…Despite the recent number of reviews on pain, its mechanism, its comorbidities, and potential therapeutics (Garcia-Larrea and Quesada, 2022;Haanpää and Treede, 2022;Hu et al, 2022;Lorente et al, 2022b;Song et al, 2022), the crosstalk between neuroinflammation, opioids and pain remains poorly understood. Nonetheless, numerous in vivo experiments in rats have shown that morphine administration provokes the release of inflammatory mediators in the dorsal horn of the spinal cord, which is a key area in pain management (Johnston, 2004;Bai et al, 2014;Tsai et al, 2016;Eidson and Murphy, 2019).…”

Sex-dependent effect of inflammatory pain on negative affective states is prevented by kappa opioid receptors blockade in the nucleus accumbens shell

“…Moreover, the MCLS seems to be involved in the modulation of negative affective states occurring in pain conditions. (Caputi et al, 2019;Jesús David Lorente et al, 2020;Massaly et al, 2019) Thereby, we measured the mRNA levels of pDYN and KOR in the NAc and the Amy by qRT-PCR together with its protein expression in these areas by ELISA and western blot.…”