A single subcutaneous saline injection, openly disclosed as a placebo, significantly reduced chronic back pain intensity at one month post-treatment compared with usual care, according to a randomized clinical trial published in JAMA Network Open.
The trial of 101 adults with chronic back pain included functional magnetic resonance imaging (fMRI) that documented increased activity in prefrontal pain-regulating regions and decreased activity in pain-processing areas, suggesting mechanisms similar to those in traditional placebo treatments.
Participants aged 21-70 years with back pain present for at least half the days in the past 6 months and a 1-week average pain intensity of ≥4/10 were recruited. The sample included 52 females and 49 males with a mean age of 40.4 years. All participants had at least some college education, with 70.6% in the open-label placebo (OLP) group being college graduates, and 70% in the usual care group. Employment status in the OLP group showed 51% working full-time, 23.5% part-time, and 25.5% unemployed, while the usual care group showed 56%, 26%, and 18%, respectively. Only 4% of participants reported current opioid use.
At one month post-treatment, 45.4% of OLP patients reported at least a 30% pain reduction and 24.4% reported at least a 50% reduction, compared with 38.3% and 14.9%, respectively, in the usual care group. The OLP group also showed improvements in pain interference and marginal improvements in anxiety. While pain relief did not persist through one-year follow-up, significant long-term benefits were observed for depression, anger, anxiety, and sleep disruption.
The neuroimaging component utilized T1 magnetization-prepared rapid gradient echo imaging and multiband echo planar imaging, with preprocessing via fMRIPrep 1.2.4. Findings revealed increased activity during evoked back pain in the ventromedial prefrontal cortex (vmPFC) and rostral anterior cingulate cortex (rACC), along with decreased activity in the primary motor cortex and thalamus. Notably, functional connectivity between the vmPFC and the rostral ventral medulla (a brainstem pain-modulatory nucleus) increased during spontaneous pain, suggesting enhanced engagement of descending pain-modulatory pathways.
The study protocol included a novel evoked pain assessment using a pneumatically controlled cylindrical balloon that delivered four randomized intensity levels of back distention. Pain ratings showed marginal reductions in the OLP group.
Study limitations included the small sample size, low racial and ethnic diversity, baseline group differences in exercise levels and pain duration, and more missing data in the usual care arm at 12-month follow-up. Additionally, the recruitment materials’ description of a mind-body intervention may have selected participants more open to placebo treatments.
Conflict of interest disclosures can be found in the study.
