Reconsolidation Therapy With Propranolol as a Treatment for Chronic Pain

Background: Many patients with chronic pain exhibit abnormal synaptic changes in the central nervous system - including hyperactivity in the amygdala - reminiscent of those seen in post-traumatic stress disorder (PTSD). A recently developed psychiatric treatment for PTSD involves reactivating the synapses to make them temporarily malleable and then blocking their reconsolidation with propranolol, thereby reducing the hyperactivity in the amygdala and decreasing the intensity of the symptoms in a lasting way. Considering the similarities between PTSD and chronic pain, this treatment could also be beneficial for patients with chronic pain.

Objectives: The primary objective of this study will be to document the feasibility and acceptability of a combined pain neuroscience education and reconsolidation blockade intervention with oral propranolol (or placebo) in adult patients with chronic pain (specifically, low back pain or fibromyalgia). The secondary objective will be to estimate the effect size of the intervention on function and pain one month post-intervention, and to obtain the data necessary for a sample size calculation of a subsequent larger scale study.

Description: The research design is a quantitative, placebo-controlled clinical trial (Phase II) feasibility study. The sample will consist of French-speaking adults with chronic low back pain or fibromyalgia (n=24 per population; 12 control and 12 experimental participants for each population; allocation by minimization); participants with a contraindication to propranolol or a neurological diagnosis will be excluded. All participants will receive education on the neuroscience of pain (video vignettes) and will participate in 6 weekly intervention sessions. During these sessions, they will receive propranolol or placebo capsules (double-blind; dosing based on size) and participate in a reactivation procedure (description and/or visualization of painful movements). Feasibility measures will be collected throughout the study; acceptability and efficacy measures will be assessed 4 weeks post-intervention, with the exception of physical function (primary efficacy measure), which will also be measured at each intervention session.

Relevance: This study will be the first to use reconsolidation blockade for the treatment of chronic pain. The postulated mechanism of action is plausible and supported by scientific evidence, but to date has never been tested in humans with persistent pain. If our results demonstrate that the intervention is feasible, acceptable, and has the potential to be effective, randomized clinical trials may follow our study to robustly evaluate the effect of our intervention in the short and long term. The intervention could also be evaluated in other chronic pain populations with central sensitization, such as pelvic pain, chronic neck pain (whiplash), etc.