Propranolol Reduces Temporomandibular Disorder Pain in People With Migraine

temporomandibular pain
temporomandibular pain, toothache, headahche,
Researchers set out to evaluate whether propranolol efficacy is greater in people with comorbid migraine compared with those without migraine.

Propranolol is more effective in reducing temporomandibular disorder (TMD) pain in people with migraine compared with people without migraine, according to research published in Cephalalgia.

Building on data collected in the SOPPRANO trial ( identifier NCT02437383), researchers set out to evaluate the 2 exploratory aims of the trial: first, whether propranolol efficacy is greater in people with comorbid migraine compared with those without and second, whether propranolol efficacy for TMD pain is mediated by headache reduction or heart rate change secondary to propranolol use.

SOPPRANO was a multi-site, double-blind, placebo-controlled, parallel-group, phase 2b clinical trial investigating the analgesic efficacy of propranolol in patients with painful TMD. A total of 200 participants with chronic myogenous TMD with or without arthralgia were enrolled, then randomly assigned 1:1 to receive either extended release propranolol 60 mg or placebo over the course of the study period.

The primary study outcome was the results of the mean weekly facial pain index as a 7-day average of the product of average facial pain intensity multiplied by pain duration.

Within the cohort, 87% of participants (primarily young White women) completed week 9 follow-up; 52% met the criteria for definite or probable migraine, and 29% and 30% of those with migraine met criteria for chronic migraine or migraine with aura. Demographic characteristics were generally similar between groups, excepting time since TMD onset — 12 years in people with migraine and 9 years in people without.

Investigators analyzed efficacy as between-group difference in facial pain index at week 9 and found a small difference for people with migraine (adjusted mean, -3.6; 95% confidence limit [CL], -9.7 to 2.4) but no difference for people without. Migraine by treatment group was not statistically significant.

A further analysis of 30% or greater reduction in facial pain intensity at week 9 found that the efficacy of propranolol was higher among people with migraine (adjusted odds ratio [aOR], 3.3; 95% CL, 1.4-8.1; P =.009; number needed to treat [NTT], 3.7) compared with people without migraine (aOR, 1.3; 95% CL, 0.5-3.2; P =.631; NNT, 18.7).

Investigators observed a similar tendency for 50% or greater reduction in facial pain intensity and found an NNT of 3.9 vs 12.5 for people with migraine vs people without (P =.260 for interaction). Odds of a 6-point or greater reduction in HIT-6 score at week 9 was higher in people with migraines than in people without (aOR, 2.8 vs 1.2).

Researchers identified a “negligible correlation” between the change in facial pain index and HIT-6 change at week 6 and week 9 (Kendall’s tau ranging from 0.09 to 0.27). Results of a causal mediation analysis with HIT-6 as a potential mediator found a weak indirect effect of treatment on 50% or greater reduction in facial pain index (OR, 1.05; 95% CL, 0.91-1.19); only 9% of the total effect was mediated by reduction in HIT-6. Comparatively, mediation analysis using heart rate as the potential mediator indicated a stronger indirect effect (OR, 1.30; 95% CL, 0.86-1.74).

Study limitations include the lack of a daily headache diary due to the focus on TMD, assessment of the effect of propranolol via the HIT-6 questionnaire, and results of mediation analyses that did not reach statistical significance.

“This [randomized controlled trial] of patients with chronic myofascial TMD demonstrated that efficacy of propranolol in reducing TMD pain was enhanced in the presence of comorbid migraine,” the researchers concluded. “Hence, propranolol appears to be the drug of choice for management of painful TMD in [people with migraines].”


Tchivileva IE, Ohrbach R, Filingim RB, et al. Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial. Cephalalgia. Published online February 9, 2021. doi:10.1177.0333102241989268