Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients

Abstract

Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. This functional magnetic resonance imaging (fMRI) study examined whether placebo analgesia is accompanied by reductions in neural activity in pain-related areas of the brain during the time of stimulation. Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat. Large reductions in pain and in brain activation within pain-related regions (thalamus, somatosensory cortices, insula, and anterior cingulate cortex) occurred during the placebo condition. Results indicate that decreases in activity were related to placebo suggestion and a second factor (habituation/attention/conditioning). Although many factors influence placebo analgesia, it is accompanied by reduction in pain processing within the brain in clinically relevant conditions.

Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging

“…Functional imaging studies using positron emission tomography and fMRI revealed that patients with IBS often have exaggerated activation of cerebral sensory areas, especially emotional areas of brain following visceral stimulation as compared to healthy subjects. [12][13][14][15][16][17][18][19][20] Evidence from these studies indicates differential activation of the anterior cingulate cortex (ACC), prefrontal cortex (PFC), thalamus, insular cortex, and other limbic brain regions during colorectal stimulation, heterotopic stimulation or rectal balloon distension in IBS patients compared with healthy subjects. [12][13][14][15]18 Furthermore, resting state fMRI study performed on IBS patients demonstrated increased spontaneous neuronal activity in visceral afferent processing regions, while decreased regional brain activity in cognitive and pain regulatory regions.…”

Unconscious and conscious mediation of analgesia and hyperalgesia

“…The increases did not occur in the IBS group not given the verbal suggestion. Taken together, these studies of IBS patients reflect the conscious cognitive nature of this form of analgesia (7)(8)(9). After all, the patients have to hear the verbal suggestion, understand its meanings, retain a working memory of it, and develop expectations and feelings about reduced pain (which they can rate on scales), unlike the mechanisms of subliminally conditioned changes in pain described by Jensen et al (1).…”

“…Although all other aspects of the placebo procedures were the same, IBS patients given the verbal suggestion had much larger placebo effects than patients not given the suggestion (7,9). When both groups were compared in fMRI analyses of brain activity, only the group receiving the verbal suggestion showed large reductions in brain activity related to processing pain (7).…”

“…It is also important to recognize that placebo and nocebo effects on pain can occur consciously and without conditioning (7)(8)(9)(10). Consciously evoked pain modulation is known to occur as a result of verbal suggestions (7-10), as well as physical simulations of active treatments (4).…”

“…First, ratings of desire for relief and expected pain predicted most of the variability in pain ratings in the placebo condition (8). Second, ratings of expected pain, desire for pain reduction, and experimentally evoked pain (from visceral distension) progressively decreased with each successive test stimulus used to measure the placebo analgesic response (7)(8)(9). This progressive increase in placebo responding has been explained by a somatic feedback mechanism in which patients' experiences of pain relief lead to still further reductions in pain during subsequent test stimuli (12).…”