期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 25, 期 7, 页码 1408-1415出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2011.04.013
关键词
Intrathecal; TLR4; Cytokines; Mechanical allodynia
资金
- NIH [DA024044, DE107782, DE020247, DA023132]
While stress and stress-induced glucocorticoids are classically considered immunosuppressive, they can also enhance proinflammatory responses to subsequent challenges. Corticosterone (CORT) primes rat immune cells, exacerbating pro-inflammatory responses to subsequent immune challenges. Stress can also sensitize pain. One possibility is that stress primes spinal immune cells, predominantly glia, which are key mediators in pain enhancement through their release of proinflammatory cytokines. Therefore, we aimed to identify whether prior CURT sensitizes spinal cord glia such that a potentiated pro-inflammatory response occurs to later intrathecal (IT) lipopolysaccharide (LPS), thereby enhancing pain. Rats received subcutaneous CORT/vehicle 24 h before IT LPS/vehicle. Hind paw pain thresholds were measured before CURT/vehicle, before and up to 48 h after IT LPS/vehicle. In separate rats treated as above, lumbar spinal cord tissue was collected and processed for proinflammatory mediators. CURT alone had no effect on pain responses, nor on any pro-inflammatory cytokines measured. LPS induced allodynia (decreased pain threshold) lasting <4 h and elevated spinal IL-1 beta and IL-6 protein. Prior CURT potentiated allodynia, lasting >24 h following LPS and potentiated spinal IL-1 beta and IL-6 protein. Coadministration of IL-1 receptor antagonist with LPS IT completely blocked the allodynia irrespective of whether the system was primed by CORT or not. At 24 h, TLR2, TLR4, MD2, and CD14 mRNAs were significantly elevated within the spinal cord in the CORT + LPS group compared to all other groups. Prior CURT before a direct spinal immune challenge is able to potentiate pain responses and pro-inflammatory cytokine production. (C) 2011 Elsevier Inc. All rights reserved.
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