Brain and psychological determinants of placebo pill response in chronic pain patients

Abstract

The placebo response is universally observed in clinical trials of pain treatments, yet the individual characteristics rendering a patient a ‘placebo responder’ remain unclear. Here, in chronic back pain patients, we demonstrate using MRI and fMRI that the response to placebo ‘analgesic’ pills depends on brain structure and function. Subcortical limbic volume asymmetry, sensorimotor cortical thickness, and functional coupling of prefrontal regions, anterior cingulate, and periaqueductal gray were predictive of response. These neural traits were present before exposure to the pill and most remained stable across treatment and washout periods. Further, psychological traits, including interoceptive awareness and openness, were also predictive of the magnitude of response. These results shed light on psychological, neuroanatomical, and neurophysiological principles determining placebo response in RCTs in chronic pain patients, and they suggest that the long-term beneficial effects of placebo, as observed in clinical settings, are partially predictable.

Identification of traits and functional connectivity-based neuropsychotypes of chronic pain

“…7). The result is consistent with our earlier report (Vachon-Presseau et al, 2018) where we observed multiple subscales of MAIA being predictive of placebo response, and these all loaded onto Aware-trait. The current result highlights the fact that chronic pain traits unrelated to pain are still relevant when studying other characteristics of patients such as the likelihood of responding to a specific treatment.…”

“…This study is based on data collected in the setting of a Randomized Control Trial (RCT) designed to study placebo pill response in chronic pain patients (Vachon-Presseau et al, 2018). Patients with chronic back pain (CBP) enrolled in the RCT visited the lab on six occasions with four visits including brain-imaging sessions ( fig.…”

“…We therefore more closely examined the associations between pain anxiety (PASS), affective qualities of back pain (MPQ/a), and general negative affect (PANAS/n), which all changed over time, independent of treatment type received or presence of placebo response (supplementary fig. 3; see (Vachon-Presseau et al, 2018) regarding the unspecific improvement of pain qualities). We observed that changes in neurotraits 1 and 2 between the first and the last fMRI sessions (V2 and V5; ΔNeurotrait 1 and ΔNeurotrait 2) were both related to ΔPASS, but not with ΔMPQ/a or ΔPANAS/n per se, suggesting that its expression pattern tracked Pain-trait related-outcomes rather than pain qualities or affect.…”

“…We further explored how the four chronic pain traits related to the response to placebo treatment during the RCT. We calculated the magnitude of placebo response as the strongest response (% change in pain) in either of the two treatment periods, as was previously done in (Vachon-Presseau et al, 2018). Interestingly, the 2 traits reflecting back pain properties of CBP, Pain-trait and Emote-trait, were unrelated to the placebo response.…”

Placebo-induced pain reduction is associated with inverse network coupling at rest

“…To further investigate placebo-induced changes in intrinsic network fluctuations, future studies should measure resting-state during placebo as well as control conditions in the same participants. Resting-state periods before and after placebo induction and pain processing might further be helpful to disentangle the effects of treatment expectations, pain anticipation and pain processing on network coupling, and to investigate trait characteristics that render individuals more or less susceptible to placebo-related belief inductions (Vachon-Presseau et al, 2018). Second, we found that inverse network coupling was positively related to individual pain intensity scores which we obtained from the preceding pain task (Fig.…”