Placebo conditioning and placebo analgesia modulate a common brain network during pain anticipation and perception

Abstract

The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p = 0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.

Placebo response to manual therapy: something out of nothing?

“…Current studies suggest that placeborelated hypoalgesia is associated with responses in regions of the brain related to pain modulation, [45][46][47] emotion, [47][48][49] and cognitive appraisal. 41,48 Both the opioid system 50,51 and the reward system 52,53 are involved in placebo-related hypoalgesia and brain imaging further supports these relationships. 54,55 Additionally, the placebo effect is significantly lessened in patients with Alzheimer's disease with pre-frontal cortex involvement 56 and can be abolished with experimental disruption of the prefrontal cortex through transcranial magnetic stimulation.…”

“…Following this type of conditioning program, the magnitude of placeborelated hypoalgesia is increased when the placebo is used with the original level of the noxious stimulus. For example, Watson et al 41 induced experimental pain in healthy participants through a serious of laser stimuli. Following baseline assessment of pain sensitivity, participants received a placebo cream with the instruction they were receiving either an analgesic agent or an inactive cream.…”

Linking Pain and the Body: Neural Correlates of Visually Induced Analgesia

“…Painful stimuli were delivered by a neodymium yttrium aluminum perovskite (Nd:YAP) laser (EL.EN. Group) with a wavelength of 1.34 m, as used in previous MRI studies of laser-induced pain (Watson et al, 2009;Ploner et al, 2011). Stimuli at four different intensities (1.5, 2.0, 2.5, and 3.0 J; 4 ms pulse duration; 6 mm beam diameter) were delivered to the dorsum of the right hand.…”

Placebo Effect in Clinical Trial Design for Irritable Bowel Syndrome

“…29 Similarity between successfully conditioned response and expectancy has been identified and validated using functional MRI which reveals similar brain activity. 30 …”