Effect of betamethasone on neuropathic pain and cerebral expression of NF-kappaB and cytokines.
Glucocorticoids have been used to treat neuropathic pain for many years, but the underlying mechanisms are still unknown. Recent studies indicate that pathological pain states may be mediated by cytokines. We, therefore, examined the effect of betamethasone on neuropathic pain and the relationship between pain behavior and the expression of cytokines in the brain. Rats were given epidural injections of betamethasone (Diprospan) after L5 spinal nerve transection. Mechanical allodynia and thermal hyperalgesia were evaluated on post-operative days 1, 3, 7, 14 and 21 with von Frey and Hargreaves tests. Cerebral expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 was quantified using electrophoretic mobility shift assay (EMSA) or enzyme-linked immunosorbent assay (ELISA). We found that spinal nerve injury caused long-lasting mechanical and thermal hyperalgesia in the hind paw and stimulated the expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 in the brain. A single epidural injection of betamethasone at the time of nerve injury partially inhibited the development of neuropathic hyperalgesia and reduced the subsequent elevated levels of pro-inflammatory cytokines in the brain, while stimulating the expression of the anti-inflammatory cytokine IL-10. These data support our hypothesis that pro-inflammatory cytokines in the brain may mediate the hyperalgesic effects of spinal nerve injury and that the long-acting anti-hyperalgesic effects of epidural glucocorticoid treatment are due to an inhibitory effect on pro-inflammatory cytokine levels and a stimulatory effect on anti-inflammatory cytokine levels in the brain.
Xie
Weiying
W
Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Liu
Xiaoming
X
Xuan
Haojun
H
Luo
Saizhen
S
Zhao
Xin
X
Zhou
Zhiqiang
Z
Xu
Jianguo
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications; D013997:Time Factors; D000097782:NF-kappaB-Inducing Kinase
D000893:Anti-Inflammatory Agents; D001623:Betamethasone; D016207:Cytokines; D004338:Drug Combinations; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C032812:betamethasone dipropionate, betamethasone sodium phosphate drug combination