TY - JOUR
T1 - A trigger for opioid misuse
T2 - Chronic pain and stress dysregulate the mesolimbic pathway and Kappa opioid system
AU - Massaly, Nicolas
AU - Morón, Jose A.
AU - Al-Hasani, Ream
N1 - Funding Information:
We would like to thank Dr. Jordan McCall and Dr. Adrianne Wilson-Poe for their helpful comments on the manuscript. This work was supported by NIDA R01 DA027460 (JM), NIDA R21 DA036826 (JM) and NIDA K99/R00 Pathway to Independence Award DA038725 (RA).
Publisher Copyright:
© 2016 Massaly, Morón and Al-Hasani.
PY - 2016
Y1 - 2016
N2 - Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.
AB - Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.
KW - Chronic pain
KW - Dopamine
KW - Kappa opioid receptor
KW - Psychological
KW - Reward
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=85009827431&partnerID=8YFLogxK
U2 - 10.3389/fnins.2016.00480
DO - 10.3389/fnins.2016.00480
M3 - Article
C2 - 27872581
AN - SCOPUS:85009827431
VL - 10
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
IS - NOV
M1 - 480
ER -