Persistent nociceptor hyperactivity as a painful evolutionary adaptation.

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.
Competing Interests: Declaration of interests T.J.P. is a co-founder of 4E Therapeutics, Doloromics, PARMedics, and NuvoNuro; he serves on the Board of Directors of 4E Therapeutics and Doloromics; he is an inventor on patents related to MNK inhibition for the treatment of pain. E.S.S. receives funding from AstraZeneca and GlaxoSmithKline. E.T.W., R.J.C., and G.G.N. declare no competing interests.
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