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.

Keywords: Addiction; Amygdala; Corticotropin-releasing factor; Nucleus accumbens; Pain; Prefrontal cortex.

Fig. 1

Persistent pain conditions (e.g., neuropathy, arthritic inflammation) originate peripherally but interact with ascending nociceptive circuitry in the spinal cord and brain via central sensitization mechanisms. Translation of chronic pain into negative affect occurs as a consequence of increased nociception-driven activity within central brain stress and reward/reinforcement circuitry, including the central amygdala. Importantly, pain-induced affective dysregulation may contribute to the transition to addiction in vulnerable individuals with a history of drug abuse. Medications targeting neuroadaptations associated with chronic pain- and drug-induced hyperalgesia may represent effective therapeutic strategies for drug and alcohol addiction.