Naltrexone during pain conditioning: A double-blind placebo-controlled experimental trial.

Naltrexone reversibly blocks the effects of opioids and has been shown to decrease placebo analgesia. However, it is not clear (1) to what extent naltrexone affects pain modulation in a nontreatment context, for example, in response to pain cues or (2) how naltrexone given prior to pain-cue learning shapes pain responses. In a double-blind procedure prior to pain-cue conditioning, 30 healthy participants were randomized to receive an oral dose of naltrexone (50 mg) or inert pill. During functional magnetic resonance imaging, high and low pain pressures were paired with two different visual cues: a high pain cue and a low pain cue (learning sequence). During a test sequence, medium levels of pressure were used for both cues and the difference in subjective pain ratings following high and low pain cues was calculated. Results showed significant conditioned pain responses across groups (P < .001); however, no significant difference between participants receiving naltrexone or inert pill (P = .193). There was a significant correlation between the difference in high and low pain ratings during the learning sequence and the effect of high and low pain cues during the test sequence (r = .575, P = .002). Functional magnetic resonance imaging analyses revealed no significant difference in brain activation between groups. Here, we demonstrate comparable learning of pain responses in participants treated with naltrexone or inert pill. The results point to the possibility that associative learning, and conditional responding to pain cues, is not dependent on endogenous opioids. Our results, using pain-cue conditioning to create reduced pain responses, contrast previous studies where opioid antagonists significantly reduced the placebo effect in treatment of pain.

Modulating pain thresholds through classical conditioning.

BACKGROUND: Classical conditioning has frequently been shown to be capable of evoking fear of pain and avoidance behavior in the context of chronic pain. However, whether pain itself can be conditioned has rarely been investigated and remains a matter of debate. Therefore, the present study investigated whether pain threshold ratings can be modified by the presence of conditioned non-nociceptive sensory stimuli in healthy participant. METHODS: In 51 healthy volunteers, pain threshold to electrocutaneous stimuli was determined prior to participation in a simultaneous conditioning paradigm. Participants underwent an acquisition phase in which one non-painful vibrotactile stimulus (CS+) was repeatedly paired with a painful electrocutaneous stimulus, whereas a second vibrotactile stimulus of the same quality and intensity (CS-) was paired with a non-painful electrocutaneous stimulus. Stimulation was provided on the lower back with close proximity between the conditioned stimulus and the unconditioned stimulus. In the test phase, electrocutaneous stimuli at the individually-set threshold intensity were simultaneously delivered together with either a CS+ or CS-. Pain intensity ratings were obtained after each trial; expectancy ratings were obtained after each block. The primary outcome was the percentage of test stimuli that were rated as painful. RESULTS: Test stimuli were more likely to be rated as painful when they were paired with the CS+ than when they were paired with the CS-. This effect was not influenced by contingency awareness, nor by expectancies or mood states. DISCUSSION: The findings support the notion that the judgement of an event being painful or non-painful can be influenced by classical conditioning and corroborate the possible role of associative learning in the development and maintenance of chronic pain.