Genetic variation in P2RX7 and pain tolerance

Area of Science:

• Neuroscience
• Genetics
• Immunology

Background:

• The P2X7 receptor, activated by extracellular ATP, is a nonselective cation channel involved in inflammation and apoptosis.
• P2X7 receptor function has been recently associated with chronic inflammatory and neuropathic pain.
• P2X7 may influence pain through peripheral tissue injury and central nervous system processing.

Purpose of the Study:

• To investigate the association between genetic variations in the P2RX7 gene and experimentally induced pain in humans.
• To further elucidate the role of the P2X7 receptor in human pain sensitivity.

Main Methods:

• Examined single-nucleotide polymorphisms (SNPs) within the P2RX7 gene in two human cohorts: Tromsø 6 (N=3016) and BrePainGen (N=831).
• Assessed experimental pain intensity and tolerance using the cold-pressor test.
• Evaluated clinical pain phenotypes including multisite chronic pain and postoperative pain intensity.

Main Results:

• The single-nucleotide polymorphism rs7958311 showed a significant association with experimental pain intensity in a meta-analysis of both cohorts.
• Significant associations were also observed between rs7958311 and multisite chronic pain, as well as postoperative pain intensity.
• SNPs rs208294 and rs208296 were also examined, though rs7958311 yielded the most robust findings.

Conclusions:

• The findings strengthen evidence suggesting that the P2X7 receptor and genetic variations in the P2RX7 gene are involved in modulating human pain sensitivity.
• Genetic variation in P2RX7 may represent a significant factor in individual differences in pain perception and clinical pain states.