Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats
Summary
It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper‐responsiveness of wide dynamic range neurons (WDR) and Toll‐like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post‐injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper‐responsiveness of WDR neurons in CCI rats. The results of this study indicate that post‐injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper‐responsiveness. This study confirms that post‐injury modulation of microglial activity is a new strategy for treating neuropathic pain.
Number of times cited: 6
- SeungHwan Lee, Xiang Qun Shi, Anni Fan, Brian West and Ji Zhang, Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain, Molecular Pain, 14, (174480691876497), (2018).
- H. Zhao, A. Alam, Q. Chen, M. A. Eusman, A. Pal, S. Eguchi, L. Wu and D. Ma, The role of microglia in the pathobiology of neuropathic pain development: what do we know?, BJA: British Journal of Anaesthesia, 10.1093/bja/aex006, 118, 4, (504-516), (2017).
- Young S. Gwak, Claire E. Hulsebosch and Joong Woo Leem, Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury, Neural Plasticity, 10.1155/2017/2480689, 2017, (1-14), (2017).
- Kathleen Meacham, Andrew Shepherd, Durga P. Mohapatra and Simon Haroutounian, Neuropathic Pain: Central vs. Peripheral Mechanisms, Current Pain and Headache Reports, 21, 6, (2017).
- Hua‐Dong Ni, Ming Yao, Bing Huang, Long‐Sheng Xu, Ying Zheng, Yu‐Xia Chu, Han‐Qi Wang, Ming‐Juan Liu, Shi‐Jie Xu and Hong‐Bo Li, Glial activation in the periaqueductal gray promotes descending facilitation of neuropathic pain through the p38 MAPK signaling pathway, Journal of Neuroscience Research, 94, 1, (50-61), (2015).
- Mahboobeh Rahbardar Ghasemzadeh, Bahareh Amin, Soghra Mehri, Seyed Javad Mirnajafi-Zadeh and Hossein Hosseinzadeh, Effect of alcoholic extract of aerial parts of Rosmarinus officinalis L. on pain, inflammation and apoptosis induced by chronic constriction injury (CCI) model of neuropathic pain in rats, Journal of Ethnopharmacology, 194, (117), (2016).
