Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan.
Toxicology. 2011 Jan 11;279(1-3):123-9. doi: 10.1016/j.tox.2010.10.002. Epub 2010 Oct 19.
An increasing amount of data show that central inflammation contributes to many debilitating diseases and produces spontaneous pain and hyperalgesia (an increased sensitivity to painful stimuli), and these processes may be associated with the production of proinflammatory cytokines by activated microglia. In the present study, we demonstrate that neonatal intracerebral injection of lipopolysaccharide (LPS) (1mg/kg) in postnatal day 5 (P5) rats produced hyperalgesia that lasted into adulthood as indicated by decreased latency in the tail-flick test. Neonatal LPS administration resulted in a long-lasting increase in the number of activated microglial in the P70 rat brain. The effects of interleukin-1beta (IL-1β) and IL-1 receptor antagonists on hyperalgesia were determined to examine the possible role of inflammatory cytokines in LPS-induced hyperalgesia. Our data show that neonatal intracerebral injection of IL-1β (1 μg/kg) produced a hyperalgesic tendency similar to that induced by LPS. Neonatal administration of an IL-1 receptor antagonist (0.1mg/kg) significantly attenuated long-lasting hyperalgesia induced by LPS and reduced the number of activated microglia in the adult rat brain. These data reveal that neonatal intracerebral LPS exposure results in long-lasting hyperalgesia and an elevated number of activated microglia in later life. This effect is similar to that induced by IL-1β and can be prevented by an IL-1 receptor antagonist. The present study suggests that an IL-1 receptor antagonist effectively attenuates or blocks long-lasting hyperalgesia and microglia activation produced by LPS exposure in the neonatal period of rats.
越来越多的证据表明，中枢炎症与许多使人虚弱的疾病有关，并导致自发性疼痛和痛觉过敏（对疼痛刺激的敏感性增加），而这些过程可能与被激活的小胶质细胞产生促炎细胞因子有关。在本研究中，我们证明了在新生后第 5 天（P5）的大鼠脑内注射脂多糖（LPS）（1mg/kg）会产生痛觉过敏，这种现象会持续到成年期，表现在甩尾试验中潜伏期的缩短。新生大鼠脑内给予 LPS 可导致 P70 大鼠脑内激活的小胶质细胞数量持续增加。通过测定白细胞介素-1β（IL-1β）和 IL-1 受体拮抗剂对痛觉过敏的影响，来检验炎症细胞因子在 LPS 诱导的痛觉过敏中的可能作用。我们的数据表明，脑内注射 IL-1β（1μg/kg）可产生类似于 LPS 诱导的痛觉过敏倾向。给予 IL-1 受体拮抗剂（0.1mg/kg）可显著减轻 LPS 诱导的长期痛觉过敏，并减少成年大鼠脑内激活的小胶质细胞数量。这些数据表明，新生大鼠脑内 LPS 暴露会导致长期痛觉过敏和成年后小胶质细胞数量增加。这种效应类似于 IL-1β 诱导的效应，并且可以被 IL-1 受体拮抗剂所预防。本研究表明，IL-1 受体拮抗剂可有效减轻或阻断 LPS 暴露诱导的大鼠新生期的长期痛觉过敏和小胶质细胞激活。
