Milligan E D, Zapata V, Chacur M, Schoeniger D, Biedenkapp J, O'Connor K A, Verge G M, Chapman G, Green P, Foster A C, Naeve G S, Maier S F, Watkins L R
Department of Psychology & the Center for Neuroscience, University of Colorado at Boulder, Boulder, CO 80309-0345, USA.
Eur J Neurosci. 2004 Nov;20(9):2294-302. doi: 10.1111/j.1460-9568.2004.03709.x.
Recent evidence suggests that spinal cord glia can contribute to enhanced nociceptive responses. However, the signals that cause glial activation are unknown. Fractalkine (CX3C ligand-1; CX3CL1) is a unique chemokine expressed on the extracellular surface of spinal neurons and spinal sensory afferents. In the dorsal spinal cord, fractalkine receptors are primarily expressed by microglia. As fractalkine can be released from neurons upon strong activation, it has previously been suggested to be a neuron-to-glial signal that induces glial activation. The present series of experiments provide an initial investigation of the spinal pain modulatory effects of fractalkine. Intrathecal fractalkine produced dose-dependent mechanical allodynia and thermal hyperalgesia. In addition, a single injection of fractalkine receptor antagonist (neutralizing antibody against rat CX3C receptor-1; CX3CR1) delayed the development of mechanical allodynia and/or thermal hyperalgesia in two neuropathic pain models: chronic constriction injury (CCI) and sciatic inflammatory neuropathy. Intriguingly, anti-CX3CR1 reduced nociceptive responses when administered 5-7 days after CCI, suggesting that prolonged release of fractalkine may contribute to the maintenance of neuropathic pain. Taken together, these initial investigations of spinal fractalkine effects suggest that exogenous and endogenous fractalkine are involved in spinal sensitization, including that induced by peripheral neuropathy.
最近的证据表明，脊髓神经胶质细胞可导致伤害性反应增强。然而，引起胶质细胞激活的信号尚不清楚。趋化因子（CX3C配体-1；CX3CL1）是一种在脊髓神经元和脊髓感觉传入神经细胞外表面表达的独特趋化因子。在脊髓背角，趋化因子受体主要由小胶质细胞表达。由于趋化因子在强烈激活时可从神经元释放，此前有人认为它是一种诱导胶质细胞激活的神经元到胶质细胞的信号。本系列实验对趋化因子的脊髓疼痛调节作用进行了初步研究。鞘内注射趋化因子可产生剂量依赖性的机械性异常性疼痛和热痛觉过敏。此外，在两种神经病理性疼痛模型：慢性压迫性损伤（CCI）和坐骨神经炎性神经病中，单次注射趋化因子受体拮抗剂（抗大鼠CX3C受体-1的中和抗体；CX3CR1）可延缓机械性异常性疼痛和/或热痛觉过敏的发展。有趣的是，在CCI后5-7天给予抗CX3CR1可降低伤害性反应，这表明趋化因子的持续释放可能有助于维持神经病理性疼痛。综上所述，这些对脊髓趋化因子作用的初步研究表明，外源性和内源性趋化因子均参与脊髓敏化，包括由周围神经病变引起的脊髓敏化。
