Genetic variation in P2RX7 and pain tolerance

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Kambur , O , Kaunisto , M A , Winsvold , B S , Wilsgaard , T , Stubhaug , A , Zwart , J A , Kalso , E & Nielsen , C S 2018 , ' Genetic variation in P2RX7 and pain tolerance ' , Pain , vol. 159 , no. 6 , pp. 1064-1073 . https://doi.org/10.1097/j.pain.0000000000001188

Title: Genetic variation in P2RX7 and pain tolerance
Author: Kambur, Oleg; Kaunisto, Mari A.; Winsvold, Bendik S.; Wilsgaard, Tom; Stubhaug, Audun; Zwart, John A.; Kalso, Eija; Nielsen, Christopher S.
Contributor: University of Helsinki, Department of Pharmacology
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Eija Kalso / Principal Investigator
Date: 2018-06
Language: eng
Number of pages: 10
Belongs to series: Pain
ISSN: 0304-3959
URI: http://hdl.handle.net/10138/285177
Abstract: P2X7 is a nonselective cation channel activated by extracellular ATP. P2X7 activation contributes to the proinflammatory response to injury or bacterial invasion and mediates apoptosis. Recently, P2X7 function has been linked to chronic inflammatory and neuropathic pain. P2X7 may contribute to pain modulation both by effects on peripheral tissue injury underlying clinical pain states, and through alterations in central nervous system processing, as suggested by animal models. To further test its role in pain sensitivity, we examined whether variation within the P2RX7 gene, which encodes the P2X7 receptor, was associated with experimentally induced pain in human patients. Experimental pain was assessed in Tromso 6, a longitudinal and cross-sectional population-based study (N = 3016), and the BrePainGen cohort, consisting of patients who underwent breast cancer surgery (N = 831). For both cohorts, experimental pain intensity and tolerance were assessed with the cold-pressor test. In addition, multisite chronic pain was assessed in Tromso 6 and pain intensity 1 week after surgery was assessed in BrePainGen. We tested whether the single-nucleotide polymorphism rs7958311, previously implicated in clinical pain, was associated with experimental and clinical pain phenotypes. In addition, we examined effects of single-nucleotide polymorphisms rs208294 and rs208296, for which previous results have been equivocal. Rs7958311 was associated with experimental pain intensity in the meta-analysis of both cohorts. Significant associations were also found for multisite pain and postoperative pain. Our results strengthen the existing evidence and suggest that P2X7 and genetic variation in the P2RX7-gene may be involved in the modulation of human pain sensitivity.
Subject: P2X7
Polymorphism
SNP
Experimental pain
Cold-pressor test
GAIN-OF-FUNCTION
P2X(7) RECEPTOR
P2X7 RECEPTOR
NEUROPATHIC PAIN
ION-CHANNEL
POLYMORPHISM
SENSITIVITY
POPULATION
SUSCEPTIBILITY
ASSOCIATION
3126 Surgery, anesthesiology, intensive care, radiology
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