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Effects of variation in the human α 2A ‐ and α 2C ‐adrenoceptor genes on cognitive tasks and pain perception
Author(s) -
Kohli Utkarsh,
Muszkat Mordechai,
Sofowora Gbenga G.,
Harris Paul A.,
Friedman Eitan A.,
Dupont William D.,
Scheinin Mika,
Wood Alastair J.J.,
Stein C. Michael,
Kurnik Daniel
Publication year - 2010
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2009.04.003
Subject(s) - dexmedetomidine , alpha 2 adrenergic receptor , cognition , affect (linguistics) , medicine , anesthesia , chronic pain , allele , effects of sleep deprivation on cognitive performance , psychology , receptor , physical therapy , psychiatry , sedation , gene , genetics , biology , communication
Background: The mechanisms underlying interindividual variability in pain perception and cognitive responses are undefined but highly heritable. α 2C ‐ and α 2A ‐adrenergic receptors regulate noradrenergic activity and are important mediators of pain perception and analgesia. We hypothesized that common genetic variants in these genes, particularly the ADRA2C 322–325 deletion variant, affect pain perception or cognitive responses. Methods: We studied 73 healthy subjects (37 Caucasians and 36 African–Americans) aged 25.4 ± 4.6 years. Pain response to a cold pressor test was measured using a 10 cm visual analog scale and again on the next day, after three infusions of the selective α 2 ‐agonist dexmedetomidine. Standardized cognitive tests were administered at baseline and after each infusion. The contribution of ADRA2C deletion genotype, dexmedetomidine concentration, and other covariates to pain perception and cognitive responses was determined using multiple linear regression models. Secondary analysis examined the effects of ADRA2A and other ADRA2C variants on pain perception. Results: ADRA2C Del homozygotes had higher pain scores in response to cold at baseline (6.3 ± 1.8 cm) and after dexmedetomidine (5.6 ± 2.2 cm) than insertion allele carriers (4.6 ± 2.1 cm [baseline] and 3.8 ± 1.9 cm [after dexmedetomidine]; adjusted P ‐values = 0.019 and 0.004, respectively). Cognitive responses were unrelated to ADRA2C Ins/Del genotype. None of the other ADRA2A and ADRA2C variants was significantly related to cold pain sensitivity before dexmedetomidine; after dexmedetomidine, ADRA2A rs1800038 was marginally associated ( P = 0.03). Conclusion: The common ADRA2C del322–325 variant affected pain perception before and after dexmedetomidine but did not affect other cognitive responses, suggesting that it contributes to interindividual variability in pain perception.