The butterfly effect and its electrical mechanism: Non-linear non-reciprocate sawtooth subthreshold oscillations deactivate nociceptors.

Abstract

Across mammalian evolution, chronic pain has no adaptive value, and in the wild, there's no evidence of its existence. Since rodents are often used to model chronic pain in humans, the question of how the peripheral somatosensory system of these animals responds to injury becomes critical to our overall translatability efforts. Over a decade of intensive work on this question has led to the discovery of the primordial systemic process that protects the mammalian peripheral somatosensory system against uncontrolled hyperexcitability, as well as its underlying electrical mechanism. Named the "butterfly effect," this two-stage process enables the appropriate animal behavioral response to injury (first stage) while evading pathology by deactivating hyperactive nociceptive neurons (second stage). This deactivation process involves the generation of subthreshold membrane sawtooth oscillations, which, rather than producing ectopic discharges, lead the cells to a quiescent state. The complex nature of this phenomenon challenges any simplistic approach to modeling and translating animal pain physiology directly into human pain pathology.