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We tested the hypothesis that stress causes generalized hyperalgesia [increased sensitivity to pain] by enhancing pronociceptive [pain promoting] effects of immune mediators [signaling molecules].

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 E(2) 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 (G(s) to G(i)), and for prostaglandin E(2), emergence of novel dependence on protein kinase C epsilon.

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.

Source: The Journal of Neuroscience, May 28, 2008. 28(22):5721-30. PMID: 18509033, by Khasar SG, Burkham J, Dina OA, Brown AS, Bogen O, Alessandri-Haber N, Green PG, Reichling DB, Levine JD. Department of Oral and Maxillofacial Surgery, University of California, San Francisco, California, USA. [E-mail: jon.levine@ucsf.edu]