Genetic variation in P2RX7 and pain

Abstract

Abstract Background and aims P2X7 is a purinoceptor and non-selective cation channel that is activated by extracellular ATP, especially in immune and glia cells. Activation of P2X7 triggers the secretion of several pro-inflammatory substances, such as IL- 1P, IL-18, TNF-α, and nitric oxide. P2X7 activation contributes to the pro-inflammatory response to injury or bacterial invasion and mediates apoptosis. It has been implicated in physiological and pathological conditions such as bone tissue remodelling, inflammation, oncogenesis, depression, and inflammatory, neuropathic and chronic pain. Here, we aim to characterize the effects of variation within the P2RX7 gene, which encodes the P2X7 receptor, on pain and opioid requirements in human patients. Methods Pain was assessed in Norwegian and Finnish cohorts. The Norwegian cohort represents the 6th wave of the Tromsø Study, a longitudinal and cross-sectional population based study (N = 3700), whereas the Finnish cohort (BrePainGen) consists of patients who underwent breast cancer surgery (N = 1000). For both cohorts, experimental pain data were analyzed. Pain intensity and tolerance were assessed with cold pressor test and after standardized noxious heat stimulation in both cohorts. In addition, data on acute postoperative pain and opioid requirements were analyzed in the BrePainGen cohort. Postoperative pain and opioid responses were followed during 20 h after surgery. In total, 29 single nucleotide polymorphisms (SNPs) in P2RX7 were genotyped and their association with outcome variables was assessed using linear regression and analysis of variances (ANOVA). Results Several P2RX7 SNPs were associated with the pain phenotypes. The strongest associations were seen with cold pain intensity and tolerance. The results of this study will be presented at the meeting. Conclusions Our results suggest that P2X7 and genetic varia-tion in the P2RX7-gene are involved in the modulation of human pain responses.