Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task

Background: Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning. Methods: We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: control-opioid, pain-opioid, control-pain, and opioid-pain. Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task. Results: HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, eta(2)(partial) = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, eta(2)(partial) = .16). Conclusions: Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli.