Prior exposure to glucocorticoids potentiates lipopolysaccharide induced mechanical allodynia and spinal neuroinflammation.
Prior exposure to glucocorticoids potentiates lipopolysaccharide induced mechanical allodynia and spinal neuroinflammation.
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DOI：
10.1016/j.bbi.2011.04.013
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发表时间：
2011-10
影响因子：
15.1
通讯作者：
Watkins, Linda R.
中科院分区：
文献类型：
--
作者：
Loram, Lisa C.;Taylor, Frederick R.;Strand, Keith A.;Frank, Matthew G.;Sholar, Paige;Harrison, Jacqueline A.;Maier, Steven F.;Watkins, Linda R.
虽然压力和压力诱导的糖皮质激素被经典地认为是免疫抑制的，但它们也可以增强对后续挑战的促炎反应。皮质酮（CORT）引发大鼠免疫细胞，加剧对随后免疫挑战的促炎反应。压力也会使疼痛敏感。一种可能性是，压力引发脊髓免疫细胞，主要是神经胶质细胞，这是通过释放促炎细胞因子增强疼痛的关键介质。因此，我们的目的是确定是否事先CORT致敏脊髓胶质细胞，使增强的促炎反应发生后鞘内（IT）脂多糖（LPS），从而增强疼痛。大鼠在IT LPS/媒介物之前24小时接受皮下CORT/媒介物。在CORT/媒介物之前、IT LPS/媒介物之前和之后48小时内测量后爪疼痛阈值。在如上处理的单独大鼠中，收集腰脊髓组织并处理促炎介质。CORT单独对疼痛反应没有影响，也没有对任何促炎细胞因子的测量。LPS诱导的异常性疼痛（痛阈降低）持续<4 h，脊髓IL-1β和IL-6蛋白升高。先前的CORT增强了异常性疼痛，在LPS后持续>24小时，并增强了脊髓IL-1和IL-6蛋白。IL-1受体拮抗剂与LPS IT联合应用可完全阻断痛觉超敏反应，而与CORT启动与否无关。24 h时，CORT+LPS组脊髓内TLR 2、TLR 4、MD 2和CD 14 mRNA水平较其他各组明显升高。在直接脊髓免疫激发之前的CORT能够增强疼痛反应和促炎细胞因子的产生。
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 CORT 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 CORT/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. CORT 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-1β and IL-6 protein. Prior CORT potentiated allodynia, lasting >24 h following LPS and potentiated spinal IL-1 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 CORT before a direct spinal immune challenge is able to potentiate pain responses and pro-inflammatory cytokine production.
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影响因子：
15.1
作者：
Alexander, Jessica K.;DeVries, A. Courtney;Kigerl, Kristina A.;Dahlman, Jason M.;Popovich, Phillip G.
通讯作者：
Popovich, Phillip G.
DOI：
10.1523/jneurosci.3447-09.2009
发表时间：
2009-11-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Loram LC;Harrison JA;Sloane EM;Hutchinson MR;Sholar P;Taylor FR;Berkelhammer D;Coats BD;Poole S;Milligan ED;Maier SF;Rieger J;Watkins LR
通讯作者：
Watkins LR
影响因子：
2.9
作者：
Arruda, JL;Sweitzer, SA;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
2.9
作者：
Milligan, ED;Mehmert, KK;Watkins, LR
通讯作者：
Watkins, LR
影响因子：
15.1
作者：
Johnson, JD;O'Connor, KA;Maier, SF
通讯作者：
Maier, SF