title: The affective dimension of pain as a risk factor for drug and alcohol addiction.
abstract: Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction.
authors.affiliation: Department of Pediatrics, Division of Hematology and Oncology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: LeBlanc
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: M Adrienne
authors.initials: MA
authors.lastname: McGinn
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Christy A
authors.initials: CA
authors.lastname: Itoga
authors.affiliation: Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA. Electronic address: sedwa5@lsuhsc.edu.
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
mesh_terms: D000339:Affect; D000437:Alcoholism / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology*; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D059350:Chronic Pain / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism / Q000523:psychology; D019964:Mood Disorders / Q000453:epidemiology / Q000523:psychology*; D009479:Neuropeptides / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D010146:Pain / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology; D017397:Prefrontal Cortex / Q000378:metabolism; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology
chemical_list: D009479:Neuropeptides; D004399:Dynorphins; D003346:Corticotropin-Releasing Hormone
keywords: Addiction; Amygdala; Corticotropin-releasing factor; Nucleus accumbens; Pain; Prefrontal cortex