Evidence for the involvement of spinal cord glia in subcutaneous formalin induced hyperalgesia in the rat

被引:314
作者
Watkins, LR
Martin, D
Ulrich, P
Tracey, KJ
Maier, SF
机构
[1] AMGEN INC, BOULDER, CO 80301 USA
[2] PICOWER INST MED RES, MANHASSET, NY 11030 USA
[3] N SHORE UNIV HOSP, MANHASSET, NY USA
基金
美国国家卫生研究院;
关键词
pain facilitation; tumor necrosis factor; interleukin-1; nerve growth factor; complement; fluorocitrate; CNI-1493; guanylhydrazone;
D O I
10.1016/S0304-3959(97)03369-1
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Subcutaneous (s.c.) injection of formalin induces a rapid and prolonged hyperalgesia across widespread areas of the body. This hyperalgesic state involves a brain-to-spinal cord pathway, likely arising from the nucleus raphe magnus. The present study examined whether subsequent activation of spinal cord glia may be critical for the hyperalgesic stale to be observed in rats. Glia were considered candidates as they can, upon activation, release a variety of substances known to be critical for the mediation of subcutaneous formalin-induced hyperalgesia including glutamate, aspartate, nitric oxide, arachidonic acid and cyclooxygenase products such as prostaglandins. This series of experiments demonstrate that formalin-induced hyperalgesia in rats can be blocked by intrathecal administration of agents that: (a) disrupt glial function (using either 1 nmol fluorocitrate which is a glial metabolic inhibitor, or 9 mu g CNI-1493 which disrupts synthesis of nitric oxide and cytokines in monocyte-derived cells; ANOVA revealed reliable group effects for each drug with P < 0.0005); or (b) disrupt the action of glial products (using 10, 50, or 100 mu g of a human recombinant interleukin-l receptor antagonist or 10 mu l antibody directed against nerve growth factor; ANOVA revealed reliable group effects for each drug with P < 0.001). Disruption appeared to be selective, as blockade of only select glial products was effective. That is, up to 120 mu g of a functional antagonist of tumor necrosis factor-alpha (TNF binding protein) and 5 mu l of an antibody against complement-3 produced no statistically reliable reduction in formalin-induced hyperalgesia. Taken together, the present series of experiments suggest an important role for spinal glial cells in the cascade of events that are initiated by descending signals following s.c. administration of formalin. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
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页码:225 / 235
页数:11
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