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


CONCLUSIONS
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.
Khasar
Sachia G
SG
Department Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Dina
Olayinka A
OA
Green
Paul G
PG
Levine
Jon D
JD
D000161:Acoustic Stimulation / Q000009:adverse effects; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006930:Hyperalgesia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D009483:Neuropsychological Tests; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013016:Sound / Q000009:adverse effects*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013997:Time Factors; D014110:Touch / Q000502:physiology
D002395:Catecholamines; D004837:Epinephrine