Persistent nociceptor hyperactivity as a painful evolutionary adaptation. Issue 3 (March 2023)

• Record Type: Journal Article
• Authors: Walters, Edgar T.; Crook, Robyn J.; Neely, G. Gregory; Price, Theodore J.; Smith, Ewan St John
• Is Part Of: Trends in neurosciences. Volume 46:Issue 3(2023)
• Page Start: 211
• Page End: 227
• Publication Date: 2023-03
• Subjects: Aplysia -- cephalopod -- chronic pain -- human -- primary afferent neuron -- spontaneous activity; Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2022.12.007
• Languages: English
• ISSNs: 0166-2236

Abstract

Highlights: Injury to the nervous system can generate chronic pain driven by persistent hyperactivity of nociceptors, sensory neurons specialized to detect damaging stimuli. Recent evidence argues against the near-universal assumption that persistent nociceptor hyperactivity and resulting chronic pain are always maladaptive. Widespread conservation of mechanisms of nociceptor function and hyperactivity are well documented, as well as distinct adaptations to divergent nociceptive needs. Persistent nociceptor hyperactivity could have evolved to drive painful hypervigilance during persistent physical impairment, enhancing survival by decreasing subsequent risk of predatory or aggressive attack. Differences between rodent and human nociceptors are consistent with the possibility that, during relatively recent evolution, nociceptors increased their susceptibility to persistent hyperactivity, increasing the propensity of humans to chronic pain. Abstract: Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal groups as a physiological response that can increase survival long after bodily injury, using both highly conserved and divergent underlying mechanisms.