Fu K Y, Light A R, Maixner W
Dental Research Center, School of Denitistry, University of North Carolina, Chapel Hill, NC 27599-7455, USA.
Neuroscience. 2000;101(4):1127-35. doi: 10.1016/s0306-4522(00)00376-6.
To determine whether initial nociceptive inputs caused by subcutaneous injection of formalin into the hindpaw are necessary and/or sufficient for allodynic behavior and microglial activation observed at one week following behavior, we examined Sprague-Dawley rats under five test conditions. Test condition 1. Formalin alone group (six rats), 5% formalin was injected subcutaneously into the dorsal side of the right hind paw. Test condition 2. Bupivacaine/Formalin group (six rats), bupivacaine was injected into the ankle area and into the site of formalin injection 10 min before formalin injection. Test condition 3. Saline/Formalin group (six rats), saline was injected 10min before formalin in the same manner as bupivacaine. Test condition 4. Formalin/Bupivacaine group 1 (six rats), bupivacaine was injected 10 min after formalin. Test condition 5. Formalin/Bupivacaine group 2 (six rats), bupivacaine was injected similarly 1h after formalin. The magnitude of paw edema and paw withdrawal thresholds to mechanical stimuli applied to the plantar surface of the injected paw and on the dorsal surface of the contralateral side were evaluated prior to and one week after formalin injection. The lumbar spinal cord was immunohistochemically processed at one week to assess the expression of a marker for activated microglia. The results showed: (i) pre-treatment with bupivacaine blocked both phases of formalin-evoked pain behaviors and the mechanical allodynia that developed one week post-formalin injection, but did not block microglial activation; (ii) treatment with bupivacaine 1h after formalin injection reduced paw edema and prevented skin ulceration, but one week allodynia and microglial activation were still present; and (iii) prolonged spinal microglial activation was not dependent on acute formalin-induced nociceptor activity, but was strongly associated with the amount of tissue destruction. Our studies suggest that: (i) the central sensitization associated with the phase II of formalin-evoked behaviors and spinal microglial activation are both necessary to permit the development of the long-term hyperalgesia produced by the subcutaneous administration of formalin into the rat's hindpaw; and (ii) acute nociceptive inputs following formalin injection are not necessary for central microglial activation that may be triggered by nerve damage or prolonged signals from peripherally inflamed tissue
为了确定后爪皮下注射福尔马林引起的初始伤害性输入对于行为后一周观察到的异常性疼痛行为和小胶质细胞激活是否必要和/或充分，我们在五种测试条件下检查了Sprague-Dawley大鼠。测试条件1. 单独福尔马林组（6只大鼠），将5%福尔马林皮下注射到右后爪背侧。测试条件2. 布比卡因/福尔马林组（6只大鼠），在注射福尔马林前10分钟将布比卡因注射到踝关节区域和福尔马林注射部位。测试条件3. 生理盐水/福尔马林组（6只大鼠），以与布比卡因相同的方式在注射福尔马林前10分钟注射生理盐水。测试条件4. 福尔马林/布比卡因组1（6只大鼠），在注射福尔马林后10分钟注射布比卡因。测试条件5. 福尔马林/布比卡因组2（6只大鼠），在注射福尔马林后1小时以类似方式注射布比卡因。在注射福尔马林前和注射后一周评估注射爪足底表面和对侧爪背表面施加机械刺激时的爪水肿程度和爪退缩阈值。在一周时对腰脊髓进行免疫组织化学处理，以评估活化小胶质细胞标志物的表达。结果显示：(i) 布比卡因预处理可阻断福尔马林诱发的疼痛行为的两个阶段以及福尔马林注射后一周出现的机械性异常性疼痛，但不阻断小胶质细胞激活；(ii) 在注射福尔马林后1小时用布比卡因治疗可减轻爪水肿并预防皮肤溃疡，但一周后的异常性疼痛和小胶质细胞激活仍然存在；(iii) 脊髓小胶质细胞的长期激活不依赖于急性福尔马林诱导的伤害感受器活动，但与组织破坏量密切相关。我们的研究表明：(i) 与福尔马林诱发行为的第二阶段和脊髓小胶质细胞激活相关的中枢敏化对于大鼠后爪皮下注射福尔马林产生的长期痛觉过敏的发展都是必要的；(ii) 福尔马林注射后的急性伤害性输入对于可能由神经损伤或来自外周炎症组织的延长信号触发的中枢小胶质细胞激活不是必要的
