Betamethasone affects cerebral expressions of NF-kappaB and cytokines that correlate with pain behavior in a rat model of neuropathy.
The objective of this study was to investigate whether corticosteroids modulate neuropathic pain by altering cerebral expression of nuclear factor-kappa B (NF-kappaB) and specific cytokines. The effects of topical betamethasone on neuropathic pain and cerebral expression of NF-kappaB and cytokines were studied in a rat model of L5 spinal nerve transaction. Behavioral testing was undertaken on days 1, 3, 7, 14, and 21 post-operation using the von Frey and Hargreaves tests. NF-kappaB activation in the brain was investigated by an electrophoretic mobility shift assay (EMSA), and cerebral expressions of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-10 (IL-10) were quantified using enzyme-linked immunosorbent assays (ELISA). Spinal nerve transection induced mechanical allodynia and thermal hyperalgesia, which were significantly ameliorated by topical injection of betamethasone around the site of injury. In addition, betamethasone reduced the activation of NF-kappaB and elevation of TNFalpha and IL-1beta, and induced the expression of IL-10 in the brain, all of which correlated with the changes of pain thresholds in rats. The results suggest that topical betamethasone injection inhibits the development and maintenance of neuropathic pain. Betamethasone may act by regulating the expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 in the brain. This study yields new insight into the mechanisms of corticosteroid action in neuropathic pain and may provide a basis for clinical pain control.
Xie
Weiying
W
Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, P.R.China. xwyxieweiying@hotmail.com
Luo
Saizhen
S
Xuan
Haojun
H
Chou
Chiuwen
C
Song
Ganlin
G
Lv
Ran
R
Jin
Yi
Y
Li
Wei
W
Xu
Jianguo
J
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008026:Ligation; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005938:Glucocorticoids; D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001623:Betamethasone