An evolutionary stress-response hypothesis for chronic widespread pain (fibromyalgia syndrome)

Pain Med. 2011 Aug;12(8):1167-78. doi: 10.1111/j.1526-4637.2011.01168.x. Epub 2011 Jun 21.


Objective: The study aimed to seek a unifying biological basis for the phenomena encompassed in fibromyalgia syndrome (chronic widespread pain and associated morbidities).

Setting: While much progress has been made in the last decade in understanding chronic widespread pain, its pathogenesis remains stubbornly obscure and its treatment difficult. Two themes are gaining currency in the field: that chronic widespread pain is the result of central sensitization of nociception, and that chronic pain is somehow related to activation of a global stress response.

Design: In this article we merge these two ideas within the perspective of evolutionary biology to generate a hypothesis about the critical molecular pathway involved in chronic stress response activation, namely substance P and its preferred receptor, neurokinin-1 (NK-1R), which has many empirically testable implications.

Conclusion: Drawing on diverse findings in neurobiology, immunology, physiology, and comparative biology, we suggest that the form of central sensitization that leads to the profound phenomenological features of chronic widespread pain is part of a whole-organism stress response, which is evolutionarily conserved, following a general pattern found in the simplest living systems.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Central Nervous System Sensitization / physiology*
  • Chronic Pain / physiopathology*
  • Chronic Pain / psychology*
  • Fibromyalgia / physiopathology*
  • Humans
  • Nociception / physiology
  • Receptors, Neurokinin-1 / metabolism
  • Stress, Psychological*
  • Substance P / metabolism


  • Receptors, Neurokinin-1
  • Substance P