Opponent appetitive-aversive neural processes underlie predictive learning of pain relief

Nat Neurosci. 2005 Sep;8(9):1234-40. doi: 10.1038/nn1527. Epub 2005 Aug 21.


Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Avoidance Learning / physiology*
  • Behavior Therapy / methods*
  • Brain / blood supply
  • Brain / physiopathology*
  • Capsaicin / adverse effects
  • Conditioning, Psychological / physiology*
  • Female
  • Functional Laterality
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods
  • Male
  • Models, Biological
  • Oxygen / blood
  • Pain / chemically induced
  • Pain Management*
  • Pain Measurement / methods
  • Reward
  • Statistics, Nonparametric
  • Time Factors


  • Capsaicin
  • Oxygen