Prayer and acute pain sensitivity in migraine and non-migraine cohorts: two assessor-blinded crossover experiments

Prayer is a widely used coping strategy that engages affective and cognitive processes implicated in pain regulation. Despite growing interest in the effects of religion and spirituality in health research, experimental evidence linking prayer to quantitative sensory outcomes in migraine remains limited. This study examined whether acute changes in cephalic pressure pain threshold (PPT) differed between personal prayer and non-spiritual reading in adults with and without migraine, analyzed as two separate crossover experiments. Two separate assessor-blinded, randomized two-period crossover experiments were conducted in Brazil, with participants recruited between September 2023 and June 2025, one including 57 adults with migraine and the other 52 adults without migraine. Participants completed two 10-minute sessions on separate study visits: self-selected personal prayer and a non-spiritual reading comparator. The primary outcome was the summed pressure pain threshold (PPT) across eight craniofacial sites, assessed before and after each intervention. Primary analyses were conducted separately by cohort using linear mixed-effects models including Intervention, Time, and their interaction, with a participant-specific random intercept. All participants with available outcome data from at least one study visit were included. In the migraine cohort ( n = 57), a significant Intervention x Time interaction was observed for total PPT (F(1, 164) = 13.11, p < 0.001). PPT increased following prayer by 47.1 kPa (95% CI, − 59.3 to 154.0; p = 0.383) and decreased following reading by 229.0 kPa (95% CI, − 335.4 to − 123.0; p < 0.001). In the non-migraine cohort ( n = 52), the Intervention x Time interaction was also significant (F(1, 149) = 14.09, p < 0.001). PPT increased following prayer by 86.3 kPa (95% CI, − 30.4 to 203.0; p = 0.146) and decreased following reading by 229.3 kPa (95% CI, − 347.1 to − 112.0; p < 0.001). In both cohorts, the differential pre-to-post responses were driven principally by significant reductions following reading, whereas increases following prayer were not statistically significant. Total cephalic PPT showed different acute responses to personal prayer and non-spiritual reading in both crossover experiments. These differences were driven principally by reductions in PPT following reading, whereas increases following prayer were not statistically significant. The findings do not establish that the observed between-condition differences were specific to prayer. Further studies should use comparison conditions more closely matched for expectancy, engagement, and personal meaning and examine repeated prayer practice alongside clinically relevant migraine outcomes to clarify the specificity and clinical relevance of these findings. ClinicalTrials.gov (NCT07143461), retrospectively registered on August 27, 2025.