Pain and suicidality: Insights from reward and addiction neuroscience

Abstract

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain-and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other “reward deficiency syndromes” and a new proposal for “enhanced anti-reward syndromes”. We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk.

Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the -Opioid Receptor

“…It affects almost one-third of Americans, with an estimated annual cost of $600 billion in treatment and lost productivity, and severely impacts quality of life, second only to bipolar disorder as the leading cause of suicide among all medical illnesses (Asmundson and Katz, 2009;Elman et al, 2013;National Institutes of Health, 2013). With pain research underfunded and clinicians undertaught on the subject, the problem of pain management is exacerbated by the lack of significant breakthrough pharmacotherapies in the past 50 years (Kissin, 2010).…”

A Systematic, Intensive Statistical Investigation of Data from the Comprehensive Analysis of Reported Drugs (CARD) for Compliance and Illicit Opioid Abstinence in Substance Addiction Treatment with Buprenorphine/naloxone

“…Bup/nal in a number and variety of forms (e.g., Suboxone R and Zubsolve R ) and methadone, are the available FDA approved MAT for opioid maintenance therapy. The success of the acute use of bup/nal during treatment is qualified by the potential for addiction liability, and the antireward effects of long-term use (Elman, Borsook, & Volkow, 2013;Hill et al, 2013).…”

Migraine and Reward System—Or Is It Aversive?

“…This is also relevant to migraine patients, as significant associations between suicide and migraine pain were identified even when controlling for concomitant psychiatric conditions [18]. Indeed, patients with severe headache had the highest risk for suicide (6.5-fold) over other chronic pain cohorts [16].…”

“…Comorbidity between chronic pain and Axis I disorders of the DSM-V (including depression, anxiety disorders, bipolar disorder, ADHD, autism spectrum disorders, and schizophrenia) has been well documented, where depression is the most common comorbidity, with some studies finding a prevalence rate approaching 100 % among clinical chronic pain samples [14]. In fact, chronic pain is second only to bipolar disorder as the major cause of suicide among all medical illnesses, and the high comorbidity of migraine with depression further highlights the importance of negative affect [15][16][17]. This is also relevant to migraine patients, as significant associations between suicide and migraine pain were identified even when controlling for concomitant psychiatric conditions [18].…”