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

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.

Pubmed ID: 16116445


  • Seymour B
  • O'Doherty JP
  • Koltzenburg M
  • Wiech K
  • Frackowiak R
  • Friston K
  • Dolan R


Nature neuroscience

Publication Data

September 29, 2005

Associated Grants

  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Avoidance Learning
  • Behavior Therapy
  • Brain
  • Capsaicin
  • Conditioning (Psychology)
  • Female
  • Functional Laterality
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Models, Biological
  • Oxygen
  • Pain
  • Pain Management
  • Pain Measurement
  • Reward
  • Statistics, Nonparametric
  • Time Factors