Glucocorticoid Inhibition of Neuropathic Hyperalgesia and Spinal Fos Expression
- 1 February 2001
- journal article
- regional anesthesia-and-pain-medicine
- Published by Wolters Kluwer Health
- Vol. 92 (2), 476-482
- https://doi.org/10.1097/00000539-200102000-00037
Abstract
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.Keywords
This publication has 19 references indexed in Scilit:
- Methylprednisolone prevents the development of autotomy and neuropathic edema in rats, but has no effect on nociceptive thresholdsPain, 1999
- Reversal of behavioural and electrophysiological correlates of experimental peripheral neuropathy by the NK1 receptor antagonist GR205171 in ratsNeuropharmacology, 1998
- Effect of tachykinin receptor antagonists in experimental neuropathic painEuropean Journal of Pharmacology, 1998
- Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of neuropathic pain in the guinea-pigNeuroscience, 1998
- The shoulder–hand syndrome after stroke: A prospective clinical trialAnnals of Neurology, 1994
- Characterization of antibodies to the rat substance P (NK-1) receptor and to a chimeric substance P receptor expressed in mammalian cellsJournal of Neuroscience, 1994
- Peripheral and central contributions to the persistent expression of spinal cord fos-like immunoreactivity produced by sciatic nerve transection in the ratBrain Research, 1993
- Receptor‐Based Pharmacokinetic‐Pharmacodynamic Analysis of CorticosteroidsThe Journal of Clinical Pharmacology, 1993
- Adjacent neuropathic hyperalgesia in rats: A model for sympathetic independent painNeuroscience Letters, 1991
- The reflex sympathetic dystrophy syndromeAmerican Journal Of Medicine, 1976