Intracellular Signalling and Chronic Pain

Stress induces a switch of intracellular signaling in sensory neurons
in a model of generalized pain.

J Neurosci. 2008 May 28;28(22):5721-30.

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 94143-0440, USA.

PMID: 18509033


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 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.