In this enlightening episode, we are joined by Dr. Bennett, who takes us through his ground-breaking research on the genetic basis of temporal summation of pain, or "wind-up". This process, where the repeated application of noxious stimuli leads to progressively increased pain perception, plays a pivotal role in various clinical pain disorders.

Dr. Bennett's team has utilized a Genome-Wide Association Study (GWAS) to reveal a significant association between human pain wind-up and the NCX3 locus, encoded by the SLC8A3 gene. Intriguingly, NCX3 null mice exhibited hypersensitivity in inflammatory and neuropathic pain models, with dorsal horn neurons showcasing increased wind-up and intracellular calcium following repetitive stimulation.

This episode discusses how the virally mediated enhanced spinal expression of NCX3 can potentially reduce central sensitization, opening up new avenues for pain management. This research underscores the role of calcium efflux as a pathway underpinning temporal summation and persistent pain, offering a promising target for therapeutic intervention.

Join us as we delve into these findings and their implications, offering valuable insights into pain perception's genetic associations.

Keywords: Dr. Bennett, Pain Perception, NCX3, Wind-up, GWAS, SLC8A3, Neuropathic Pain, Inflammatory Pain, Central Sensitization, Genetics of Pain.

Sodium-calcium exchanger-3 regulates pain ‘‘wind- up’’: From human psychophysics to spinal mechanisms https://doi.org/10.1016/j.neuron.2022.05.017