Effect of catechol-O-methyltransferase polymorphism on response to propranolol
therapy in chronic musculoskeletal pain: a randomized, double-blind,
placebo-controlled, crossover pilot study.
Author(s): Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W.
Affiliation(s): Center for Neurosensory Disorders, School of Dentistry, University of North
Carolina, Chapel Hill, NC 27599-7450, USA. firstname.lastname@example.org
Publication date & source: 2010, Pharmacogenet Genomics. , 20(4):239-48
INTRODUCTION: Three common haplotypes in the gene encoding
catechol-O-methyltransferase (COMT) have been associated with pain modulation and
the risk of developing chronic musculoskeletal pain, namely temporomandibular
disorder (TMD). Haplotypes coding for higher enzymatic activity were correlated
with lower pain perception. Rodent studies showed that COMT inhibition increases
pain sensitivity through beta2/3-adrenergic receptors. We hypothesized that the
nonselective beta-adrenergic antagonist propranolol will reduce clinical and
experimental pain in TMD patients in a manner dependent on the individuals' COMT
METHODS: Forty Caucasian female participants meeting the Research Diagnostic
Criteria for TMD were genotyped for COMT polymorphisms and completed a
randomized, double-blind, placebo-controlled, two-period crossover pilot study.
Each period consisted of a baseline assessment week followed by an intervention
week (propranolol or placebo). Changes in clinical pain ratings, psychological
status, and responses to heat and pressure stimuli between baseline and
intervention weeks were compared across periods.
RESULTS: The number of patients reporting a reduction in pain intensity rating
was greater during propranolol treatment (P=0.014) compared with placebo.
Propranolol significantly reduced a composite pain index (P=0.02) but did not
decrease other clinical and experimental pain ratings. When stratified by the
COMT high activity haplotype, a beneficial effect of propranolol on pain
perception was noted in patients not carrying this haplotype, a diminished
benefit was observed in the heterozygotes, and no benefit was noted in the
CONCLUSION: COMT haplotypes may serve as genetic predictors of propranolol
treatment outcome, identifying a subgroup of TMD patients who will benefit from