Genetic variation in a gene, P2RX7, affects how different people sense pain, reports a paper published online this week in Nature Medicine. Individual variations in pain sensation and responses to pain-relieving drugs make pain clinical trials quite challenging to interpret, and these findings could aid in the development of personalized pain therapeutics for patients based on this gene variant status.
Jeff Mogil, Michael Salter and colleagues looked at different pain sensitivities in a large number of mouse strains and linked the differences observed to a mutation in the mouse P2rx7 gene. They found that one variant of the gene allowed P2X7, a receptor that functions as an ion channel in the cell membrane, to form a large pore. Mice with this variant exhibited more pain than mice without this variant, and a peptide that blocked pore formation reduced pain only in mice with the larger pore-forming variant.
Salter and colleagues then extended the findings to humans, showing that individuals with post-mastectomy pain or arthritis exhibited less pain if their P2RX7 gene variant did not encode the P2X7 variant with the larger pore.