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- Title
Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain.
- Authors
Khasar, Sachia G.; Burkham, Jennifer; Dina, Olayinka A.; Brown, Adrienne S.; Bogen, Oliver; Alessandri-Haber, Nicole; Green, Paul G.; Reichling, David B.; Levine, Jon D.
- Abstract
Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E2 or epinephrine. This enhancement, which developed more than a week after exposure to stress, required concerted action of glucocorticoids and catecholamines at receptors located in the periphery on sensory afferents. The altered response to pronociceptive mediators involved a switch in coupling of their receptors from predominantly stimulatory to inhibitory G-proteins (Gs to Gi), and for prostaglandin E2 , emergence of novel dependence on protein kinase Cϵ. Thus, an important mechanism in generalized pain syndromes may be stress-induced coactivation of the hypothalamo-pituitary-adrenal and sympathoadrenal axes, causing a long-lasting alteration in intracellular signaling pathways, enabling normally innocuous levels of immune mediators to produce chronic hyperalgesia.
- Subjects
PROTEIN kinases; RHEUMATOID arthritis; PROTEIN kinase C; AUTOIMMUNE diseases; ADRENOCORTICAL hormones; FIBROMYALGIA
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 22, p5721
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0256-08.2008