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.

The association between psychosis and severe pain in community-dwelling adults: Findings from 44 low- and middle-income countries

“…Conducting analyses with more detailed information may have led to a better understanding of the association between psychosis and pain. Furthermore, information was lacking on potential confounders such as PTSD, childhood adversities, and drug dependence, which are known to be associated with both psychosis and pain (Asmundson et al, 2002;Degenhardt et al, 2015;LeBlanc et al, 2015;Matheson et al, 2013;SchellerGilkey et al, 2004;Stickley et al, 2015). Thus, their independent and potentially confounding effects remain unknown.…”

Reduced sensitivity to ethanol and excessive drinking in a mouse model of neuropathic pain

“…The affective dimension of pain may represent a risk factor for AUD (reviewed in LeBlanc et al). Here, the general assumption is that the affective perception of pain during a chronic pain condition might be the driving force to consume alcohol.…”

Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent and Non-Dependent Rats

“…Chronic pain in particular can engender a sustained negative affective state and a reorganization of cognitive strategies to avoid pain, while relief from pain is rewarding (Becerra and Borsook, 2008; Porreca and Navratilova, 2017). It is thus hypothesized that the emergence of painful states following chronic or excessive opioid exposure facilitates negative reinforcement processes whereby individuals seek relief from pain by escalating their opioid use, culminating in the development of psychiatric sequelae including opioid use disorder (Shurman et al, 2010; LeBlanc et al, 2015). Recent efforts toward understanding these processes have established operant methods to measure pain-related behaviors in rodents (e.g., King et al, 2009), with the hope of providing additional construct and translational validity with regard to the interaction of pain and motivational (or goal-directed) behavior.…”