Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines

J Pain. 2009 Oct;10(10):1073-7. doi: 10.1016/j.jpain.2009.04.005. Epub 2009 Jul 2.


Although stress plays an important role in chronic widespread pain syndromes, such as fibromyalgia, the underlying mechanism has remained elusive. We have recently demonstrated, in a model of chronic widespread pain, that prolonged enhancement of immune mediator hyperalgesia, induced by unpredictable sound stress, requires a contribution of both the sympathoadrenal (epinephrine) and the hypothalamic-pituitary adrenal (corticosterone) neuroendocrine stress axes. Because this stress protocol produced sustained elevation of plasma epinephrine, in the current study we tested the hypothesis that the sympathoadrenal axis also plays a role in maintenance of symptoms in this model of chronic widespread pain. After establishment, adrenal medullectomy abolished the enhancement of epinephrine-induced cutaneous and muscle hyperalgesia. Administration of stress levels of epinephrine to adrenal medullectomized rats reconstituted the pain phenotype. These observations suggest that the sympathoadrenal stress axis plays a major role in the induction as well as maintenance of stress-induced enhancement of mechanical hyperalgesia, mediated by prolonged elevation of circulating epinephrine.

Perspective: We present data showing mechanical hyperalgesia persisting for up to 28 days after exposure to sound stress, with evidence that the sympathoadrenal axis mediator epinephrine plays a major role. These findings could have clinical implications with regard to novel potential treatments for chronic widespread pain syndromes, such as fibromyalgia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Adrenal Medulla / metabolism*
  • Animals
  • Catecholamines / blood
  • Catecholamines / metabolism*
  • Catecholamines / pharmacology
  • Chronic Disease
  • Disease Models, Animal
  • Epinephrine / blood
  • Epinephrine / metabolism
  • Epinephrine / pharmacology
  • Hyperalgesia / complications
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology*
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Male
  • Neuropsychological Tests
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Physical Stimulation / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Sound / adverse effects*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology*
  • Sympathetic Nervous System / metabolism*
  • Time Factors
  • Touch / physiology


  • Catecholamines
  • Epinephrine