title: Systemic glucocorticoid therapy reduces pain and the number of endoneurial tumor necrosis factor-alpha (TNFalpha)-positive mast cells in rats with a painful peripheral neuropathy.
abstract: Clinical and experimental evidence suggests that glucocorticoids may be effective in the treatment of neuropathic pain, but their mechanism of action is unknown. We gave triamcinolone (3 mg/kg) to rats with an experimental post-traumatic painful peripheral neuropathy, chronic constriction injury (CCI), five days after nerve injury, when the abnormal pain syndrome is known to be present; and pain sensitivity was measured on postoperative days 7 - 14, a period during which symptoms are known to be at approximately peak severity. Additional CCI rats were treated similarly; and then they were sacrificed five days after the injection for an immunocytochemical analysis of endoneurial tumor necrosis factor-alpha (TNFalpha), macrophages, and mast cells in the sciatic nerve proximal to the site of injury. Vehicle-injected CCI rats demonstrated the expected neuropathic pain symptoms. Triamcinolone-treated CCI rats had a statistically significant reduction in the magnitude of heat-hyperalgesia and mechano-allodynia, but there was no effect on cold-allodynia or mechano-hyperalgesia. On the nerve-injured side of vehicle-injected rats, TNFalpha was present in Schwann cells and mast cells. On the nerve-injured side of triamcinolone-treated rats, there was a significant (71.5%) reduction in the number of TNFalpha-positive mast cells. Our results suggest that glucocorticoid therapy for neuropathic pain may work via the reduced expression of TNFalpha in endoneurial mast cells.
authors.affiliation: Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. hayashi-rsr@dune.ocn.ne.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Hayashi
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xiao
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Osafumi
authors.initials: O
authors.lastname: Yuge
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D005938:Glucocorticoids / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000276:immunology / Q000601:surgery; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D012585:Sciatica / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors; D014221:Triamcinolone / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D014221:Triamcinolone