Fecho Karamarie, Manning Elizabeth L, Maixner William, Schmitt Charles P
Department of Anesthesiology, Division of Pain Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Brain Behav Immun. 2007 Jan;21(1):68-78. doi: 10.1016/j.bbi.2006.02.003. Epub 2006 Apr 17.
The present study used inbred, histocompatible Fischer 344 (FIS) and Lewis (LEW) rats to begin to explore the role of the hypothalamic-pituitary-adrenal (HPA) axis in the immune processes and pain behavior associated with the carrageenan model of acute hindpaw inflammation. Because the HPA axis contributes in part to morphine's analgesic and immunomodulatory properties, the present study also assessed the effects of morphine in carrageenan-inflamed LEW and FIS rats. The results showed that carrageenan-induced hindpaw swelling and pain behavior were greater in FIS than in LEW rats. The enhanced hindpaw swelling in FIS rats correlated with an increase in myeloperoxidase (MPO; a measure of neutrophils) in the inflamed hindpaw. FIS rats showed lower circulating levels of TNFalpha, higher IL-6 levels, and similar IL-1beta and nitric oxide levels, when compared to LEW rats. Morphine produced a significant decrease in carrageenan-induced hindpaw swelling and MPO in both strains, but morphine did not significantly alter circulating cytokine/mediator levels. Morphine's analgesic effects were greater in the inflamed than the noninflamed hindpaw, and they did not correlate with morphine's anti-inflammatory effects. In fact, low doses of morphine produced a mechanical allodynia and hyperalgesia in the noninflamed hindpaw of FIS, but not LEW, rats. These results suggest a positive relationship between HPA axis activity and acute inflammation and inflammatory pain. In contrast, little evidence is provided for HPA axis involvement in morphine's anti-inflammatory or analgesic effects.
本研究使用近交、组织相容性匹配的Fischer 344（FIS）大鼠和Lewis（LEW）大鼠，开始探索下丘脑-垂体-肾上腺（HPA）轴在与角叉菜胶诱导的急性后爪炎症模型相关的免疫过程和疼痛行为中的作用。由于HPA轴部分地促成了吗啡的镇痛和免疫调节特性，本研究还评估了吗啡对角叉菜胶诱发炎症的LEW和FIS大鼠的影响。结果显示，角叉菜胶诱导的后爪肿胀和疼痛行为在FIS大鼠中比在LEW大鼠中更严重。FIS大鼠后爪肿胀增强与炎症后爪中髓过氧化物酶（MPO；中性粒细胞的一种测量指标）增加相关。与LEW大鼠相比，FIS大鼠循环中的TNFα水平较低、IL-6水平较高，而IL-1β和一氧化氮水平相似。吗啡使两种品系大鼠角叉菜胶诱导的后爪肿胀和MPO显著降低，但吗啡并未显著改变循环中的细胞因子/介质水平。吗啡在炎症后爪中的镇痛作用比在未发炎后爪中更强，且其镇痛作用与抗炎作用不相关。事实上，低剂量吗啡在FIS大鼠而非LEW大鼠的未发炎后爪中产生了机械性异常性疼痛和痛觉过敏。这些结果提示HPA轴活性与急性炎症及炎性疼痛之间存在正相关关系。相反，几乎没有证据表明HPA轴参与了吗啡的抗炎或镇痛作用。
