Corticosteroids are probably an effective treatment for some types of
neuropathic pain and
complex regional pain syndromes. This study examined the effects of systemic
methylprednisolone (MP) on acute nociception and on
pain behavior and
hyperalgesia in normal and neuropathic rats. There was no dose-response to intraperitoneal MP (up to 12 mg/kg) for nociceptive thresholds to heat (Peltier) or mechanical (analgesy-meter and von Frey fibers) stimuli in normal rats. Chronic high dose MP (3 mg/kg per day for 21 days) also had no effect on acute nociceptive thresholds in normal rats. After sciatic nerve section in rats a saphenous nerve mediated
hyperalgesia to heat and mechanical stimuli gradually developed over 21 days. High dose MP (3 mg/kg per day for 21 days) had no effect on this adjacent neuropathic
hyperalgesia. When systemic MP was started immediately after bilateral sciatic and saphenous nerve transection there was a dose-dependent reduction in autotomy behavior.
Substance P has been proposed as a mediator of
neuropathic pain and
edema. Single dose MP (12 mg/kg) slightly reduced the
substance P mediated extravasation induced with electrical stimulation of the saphenous nerve. Chronic MP (3.4 mg/kg per day for 28 days) severely reduced the neurogenic extravasation induced with saphenous nerve stimulation. Sciatic sectioned rats developed hindpaw
edema between 7 and 14 days after surgery, and this neuropathic
edema did not develop in rats chronically treated with MP (3.4 mg/kg per day). These results demonstrate that
corticosteroids did not affect nociceptive thresholds in normal or neuropathic hyperalgesic rats. Chronic
steroid treatment did prevent the development of autotomy and neuropathic
edema, and completely blocked neurogenic extravasation, findings consistent with the hypothesis that primary afferent
substance P release mediates autotomy
pain behavior and neuropathic
edema. This may be a relevant model for examining the effects of
corticosteroids on
neuropathic pain and
complex regional pain syndromes.