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*Department of Functional Restoration, Stanford University School of Medicine, Stanford, California, and Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Department of Anesthesia, Stanford University School of Medicine, Stanford, California, and Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and Magill Department of Anaesthetics, Imperial College School of Medicine, London, UK
Address correspondence and reprint requests to Wade S. Kingery, MD, Physical Medicine and Rehabilitation Service 117, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304. Address e-mail to wkingery{at}leland.stanford .edu.
Glucocorticoids are used to treat patients suffering from neuropathic pain and complex regional pain syndromes (CRPS). Previously we found that once-daily injections of the glucocorticoid methylprednisolone had no antihyperalgesic effect in the rat sciatic nerve transection model for CRPS, but on the basis of CRPS clinical data, we hypothesized that a continuous infusion of methylprednisolone might prove effective. We further postulated that the antihyperalgesic effects of glucocorticoids were mediated by the inhibition of spinal neuron hyperactivity and by the depletion of substance P or its NK1 receptor. This study tested the effects of continuously infused methylprednisolone in sciatic nerve-transected rats. Continuous infusion of methylprednisolone (3 mg · kg-1 · d-1 for 21 days), started after the development of neuropathic hyperalgesia, reversed both heat and mechanical hyperalgesia over 2 wk, and this effect persisted for at least 1 wk after discontinuing methylprednisolone. In addition, continuous methylprednisolone infusion partially reversed nerve injury-evoked Fos expression in the dorsal horns, suggesting that glucocorticoids can inhibit the spinal neuron hyperactivity induced by chronic sciatic nerve transection. Finally, no changes were observed in spinal substance P or NK1 immunoreactivity after chronic methylprednisolone infusion, suggesting that the depletion of this neuropeptide or its receptor does not contribute to the antihyperalgesic actions of glucocorticoids.
Implications: Chronic continuous infusion of the glucocorticoid, methylprednisolone, relieved pain in a rodent model of nerve injury, and this effect persisted after discontinuing the drug. Methylprednisolone may be a curative treatment for some types of neuropathic pain when administered in divided daily doses over several weeks.
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