What can evolutionary theory tell us about chronic pain?

It is 150 years since Darwin published On the origin of species, but his insights and others that followed are underused in the study of pain.Understanding of evolutionary processes could help us frame questions and interpret data more coherently, and could provide a translational framework across research endeavours.Common misconceptions about how natural selection operates are widespread; conditions that cause suffering -often painful diseases -are presented as unanswerable challenges to evolutionary theory, but genes spread when they confer a reproductive advantage and/or survival advantage, not because they guarantee health and happiness.6Some of those advantages applied in our ancestral environment but not our current environment; some came with disadvantages which did not outweigh the advantages (in the ancestral environment).In the field of pain, an explicitly evolutionary framework is rare in developing models or investigating behavior, with some notable exceptions.21,31,32Pain research (and medical research in general25) largely targets questions concerning (mechanisms rather than those concerning function, in contrast, for instance, to research on social behaviors such as empathy and altruism26.Over evolutionary time, injuries from predatory attacks, intra-species conflict and environmental hazards represent a threat to survival and thus lie at the cutting edge of selection pressures.How can we account for our behavior in relation to injury and pain, and the behavior of animals that we use in pain research?The emotional dimension of pain, established in the IASP definition,13 and given prominence in some models of pain5,32 and in some clinical settings, is often neglected in nonhuman animal research, despite striking commonalities of behavior.4,19,21Emotions, not least negative ones, can be conceptualized as serving to organize and guide goal-directed action, particularly when goals conflict.24The relative neglect of motivation in animals obscures possible continuities in behavior, yet across studies of pain in non-human animals (albeit very unevenly covered) such as cephalopods, crustaceans, fish, and particularly in farmed animals and laboratory rodents among mammals,1,28,32 shared patterns of behavior are described post-injury: reduced foraging and exploratory activity, sparing or guarding the injured area or limb, and memory for and avoidance of cues associated with the injury.32Those working with invertebrate models in particular (such as Aplysia e.g.Walters & Moroz (2009)33 or crustaceans e.g.Dyuizen et al. (2012)9) emphasize evolutionarily conserved mechanisms and genes across phyla.Behavior is very hard to reconstruct from fossil evidence, yet natural selection often acts directly on behavior, which in turn arises from the physiological, cognitive and emotional phenotype of the animal in question, and ultimately from its genotype.The parsimonious assumption must be that not only anatomy and physiology are the result of natural selection, but behavior also.29In an overview of evolutionary theory applied to medicine, Nesse and Stearns25 propose four explanations of "why natural selection has left the body vulnerable to disease".The four explanations fall into two categories (see p3825).Selection is slow covers the explanations that (1) our evolution has left us with mismatches with the modern environment; and (2) that pathogens coevolve with their hosts.Selection is limited covers the explanations that (3) there are constraints on what selection can do, or levers for it to act on; and (4) that there are trade-offs between benefits of different characteristics.They add two further points to correct common misunderstandings: that selection maximizes reproductive success, not overall health; and that the usefulness of defences such as pain and fever outweighs the suffering they cause.The last encapsulates the common belief that acute pain is purposeful whereas chronic pain is