Methylprednisolone prevents the development of autotomy and neuropathic edema in rats, but has no effect on nociceptive thresholds.
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.
Kingery
Wade S
WS
Department of Functional Restoration, Stanford University, Stanford, CA 94305; Physical Medicine and Rehabilitation Service (117), Palo Alto VA Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA School of Health Sciences, Universidad Rey Juan Carlos, Móstoles, España; Agencia de Evaluación de Tecnologías Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain Department of Anesthesiology, Stanford University, Stanford, CA 94305; Anesthesiology Service, Palo Alto VA Health Care System, Palo Alto, CA 94304, USA.
Castellote
Juan M
JM
Maze
Mervyn
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019771:Axotomy; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy* / Q000517:prevention & control; D005070:Evans Blue / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000502:physiology; D006614:Hindlimb; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D020078:Neurogenic Inflammation / Q000188:drug therapy; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000503:physiopathology / Q000601:surgery; D013373:Substance P / Q000502:physiology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D013373:Substance P; D005070:Evans Blue; D008775:Methylprednisolone