81: The pursuit of motivational goals reduces pain through an opioidergic mechanism

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Pharmacological interventions, Assessment and Measurement of Pain/Nociception, Behavioral studies

Background and Aims: Pain acts as a motivational signal to protect the organism from further harm. At the same time, it can conflict with the pursuit of other behaviorally relevant goals. The motivation–decision framework (Fields, 2006) proposes that choosing to pursue an alternative motivational goal attenuates pain via engagement of the descending pain modulatory system (DPMS). We tested whether actively deciding to pursue a motivational goal reduces pain in humans and whether this effect depends on endogenous opioids.

Methods: In a randomized, placebo-controlled, within-subject pharmacological fMRI study, 49 participants completed a motivation–decision task in two separate sessions, once under saline and once under the opioid antagonist naloxone. Participants accepted or declined calibrated monetary offers while receiving calibrated heat pain. Identical post-decision stimuli enabled isolation of decision-related pain modulation. Behavioral ratings and rACC–PAG activation and connectivity were analyzed.

Results: Pain was significantly reduced following accepted versus declined decisions for identical stimuli. Naloxone attenuated this hypoalgesic effect. Accepted decisions under saline increased rACC activation and rACC–PAG functional connectivity during pain. Both effects were blocked under naloxone.

Conclusions: We found that actively deciding to pursue a motivational goal reduces perceived pain in humans. This decision-dependent hypoalgesia engages the descending pain modulatory system, reflected in increased rACC activation and enhanced rACC–PAG functional connectivity, and is attenuated by opioid receptor blockade. These findings provide convergent behavioral, pharmacological, and neuroimaging evidence that volitional goal pursuit recruits an endogenous opioid–mediated top-down mechanism to modulate pain. The results support motivation–decision models of pain (Fields, 2006) and highlight a neurobiological pathway through which internally generated goals can flexibly regulate pain experience.

References: H. Fields, A motivation-decision model of pain: The role of opioids. Proceedings of the 25 11th World Congress on Pain, 449–459 (2006).

Presenting Author: Leonard Asan
Submitting Author: Leonard Asan

Senior Author: Christian Büchel

IASP 2026 Global Year theme of Neuropathic Pain: No

• Ole Goltermann: MSc - University Medical Center Hamburg-Eppendorf
• Lars Keuter: MSc - University Medical Center Hamburg-Eppendorf
• Jonathan Jeßberger: NA - University Medical Center Hamburg-Eppendorf
• Christian Büchel: Prof. Dr. - University Medical Center Hamburg-Eppendorf