Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study

Ruth Moont, Yonatan Crispel, Rina Lev, Dorit Pud, David Yarnitsky

Research output: Contribution to journalArticlepeer-review


For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. The orbitofrontal cortex and the amygdala seem to play a pivotal early role in pain inhibition under conditioned pain modulation.

Original languageEnglish
Pages (from-to)1469-1477
Number of pages9
Issue number7
StatePublished - Jul 2011


  • Conditioned pain modulation (CPM)
  • Diffuse noxious inhibitory controls (DNIC)
  • Endogenous analgesia
  • Low-resolution brain electromagnetic tomography (LORETA)
  • Pain-evoked potentials
  • Source localization

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine


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