The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection

• Published in: Experimental neurology Vol. 241; pp. 159 - 168
• Main Authors: Wei, Xu-Hong, Na, Xiao-Dong, Liao, Guang-Jie, Chen, Qiu-Ying, Cui, Yu, Chen, Feng-Ying, Li, Yong-Yong, Zang, Ying, Liu, Xian-Guo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2013; Elsevier
• Subjects: Activating Transcription Factor 3 - metabolism; Analysis of Variance; Animals; Antibodies; Biological and medical sciences; CD11b Antigen - metabolism; Disease Models, Animal; DRG; Functional Laterality; Hyperalgesia - etiology; Injuries of the nervous system and the skull. Diseases due to physical agents; Interleukin-6; Interleukin-6 - metabolism; L5 ventral root transection; Lectins - metabolism; Male; Medical sciences; Nerve Tissue Proteins - metabolism; Neuralgia - etiology; Neuralgia - pathology; Neurology; Neuropathic pain; Pain Threshold - physiology; Polyradiculopathy - complications; Polyradiculopathy - etiology; Rats; Rats, Sprague-Dawley; Spinal dorsal horn; Spinal Nerve Roots - metabolism; Spinal Nerve Roots - pathology; Spinal Nerves - injuries; Time Factors; TNF-α; Traumas. Diseases due to physical agents; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - physiology; DRG; Spinal dorsal horn; L5 ventral root transection; TNF-α; Interleukin-6; Neuropathic pain; Spinal cord; Nervous system diseases; Cytokine; Central nervous system; Posterior spinal horn; Interleukin 6; Pain; Neuralgia; Neurological disorder; Tumor necrosis factor α
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2012.12.007

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6. ► Motor fiber injury by L5-VRT induces IL-6 up-regulation in DRGs and spinal cord. ► Increased IL-6 located in DRG neurons and spinal glial cells and spinal neurons ► L5-VRT induces the mechanical allodynia in bilateral hindpaws. ► Spinal IL-6 neutralizing antibody delays the induction of allodynia by L5-VRT. ► Inhibition of TNF-α synthesis prevents the IL-6 increase in DRGs following L5-VRT.