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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.

An experimental mononeuropathy was produced in rats by unilateral loose ligation of the sciatic nerve, with a contralateral sham surgery. Repeated bilateral sensory testing was performed over time to investigate any threshold differences between the loose ligature side and the contralateral control side. A prolonged reduction in the mean withdrawal threshold to heat was observed on the loose ligature side over the medial dorsum of the hindpaw (MDH), and over the plantar surface of the hindpaw (PSH). Following loose ligature there was also a significant reduction in the von Frey fiber withdrawal thresholds over the lateral dorsum of the hindpaw (LDH) and the medial dorsum of the hindpaw (MDH). In a second experiment the saphenous nerves were transected bilaterally in rats who had an earlier unilateral loose sciatic ligation. The heat hyperalgesia that had been previously observed over the MDH was abolished, and no withdrawal response could be elicited with the largest von Frey fiber over the MDH, indicating that the MDH hyperalgesia induced by sciatic loose ligature was mediated by the saphenous nerve. This adjacent neuropathic hyperalgesia (ANH) resembles the saphenous mediated ANH observed over the MDH following sciatic transection, follows the same temporal course of onset, and may share a similar pathogenesis. The heat threshold over the PSH and the pressure threshold over the LDH were unaffected by the bilateral saphenous transection, demonstrating that following loose sciatic ligation both of these thresholds are mediated by the sciatic nerve.