Reconsolidation blockade with propranolol as a novel treatment for chronic low-back pain: a double-blind randomized placebo-controlled feasibility study

Purpose: Nociplastic pain is often characterized by maladaptive plasticity in the nervous system similar to that observed in patients with post-traumatic stress disorder (PTSD). The aim of this study was to investigate whether reconsolidation therapy, a treatment for PTSD consisting in reactivating (through trauma narrative) the synapses encoding the excessive threat response and blocking their reconsolidation using propranolol, is feasible in patients with nociplastic low-back pain. Patients and methods: Design: triple-blind, placebo-controlled feasibility study. Population: 24 adults with chronic (>6 months) nociplastic low-back pain with no comorbid PTSD or contra-indication to propranolol. Intervention: Pain education (10 short videos) and 6 weekly sessions of reconsolidation therapy with propranolol (n=12) or placebo (n=12) administered orally 1h pre-reactivation). Outcome measures: Feasibility: recruitment rates, adverse events (frequency/severity). Effect of intervention: Brain Pain Inventory (BPI) and other self-reported pain questionnaires, 4 weeks post-intervention.

Sixty-six patients were screened over 6 months; 24 participants were enrolled; 2 dropped out. Adverse events were mild and infrequent (asymptomatic decrease in heart rate (n=4), headache and nausea (n=1). No clinically meaningful difference was observed between the two groups on the pain questionnaires. However, we noted prevalent catastrophic/kinesiophobic discourse during the sessions, and the reactivation methods appeared to have been suboptimal for the population.

Reconsolidation therapy is a feasible intervention for chronic pain. Preliminary results suggest no effect on pain symptoms. Additional studies are warranted to assess the adequacy of reactivation procedures (proper reactivation being required to trigger reconsolidation), and to investigate whether the absence of negative pain beliefs might be a prerequisite (unmet in this study) for the success of the intervention. Competing Interest Statement AB teaches reconsolidation therapy for the treatment of PTSD. There are no other conflicts of interest to declare. Clinical Trial NCT05085782 Funding Statement The first author (ACL) is supported by a Fellowship from the Canadian Institutes of Health Research Fellowship; the study was funded by the Quebec Pain Research Network (Fonds de recherche du Quebec en Sante); and GL received salary support by the Fonds de recherche du Quebec en Sante (Senior Clinical Research Scholar). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional Ethics committee (comite d'ethique de la recherche du Centre integre universitaire de sante et de services sociaux de l'Estrie, Centre hospitalier universitaire de Sherbrooke de l'Estrie, Centre hospitalier universitaire de Sherbrooke) gave ethical approval for this work, and Health Canada (Division 5) game approval for this work in the form of a NOL (non objection letter) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Additions to acknowledgement section; figure revisions Data Availability All data produced in the present study are available upon reasonable request to the authors