title: Suppression of MyD88-dependent signaling alleviates neuropathic pain induced by peripheral nerve injury in the rat.
abstract: MyD88 is the adaptor protein of MyD88-dependent signaling pathway of TLRs and IL-1 receptor and regulates innate immune response. However, it was not clear whether and how MyD88 and related signaling pathways in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) are involved in neuropathic pain.
  
  
  
  Chronic constriction injury (CCI) was used to induce neuropathic pain in the rat. The expression of MyD88, TRIF, IBA1, and GFAP was detected with immunofluorescent staining and Western blot. The expression of interleukin-1 beta (IL-1β), high mobility group box 1 (HMGB1), NF-κB-p65, phosphorylated NF-κB-p65, ERK, phosphorylated ERK, and tumor necrosis factor-alpha (TNF-α) was detected with Western blot. Pain-related behavioral effects of MyD88 homodimerization inhibitory peptide (MIP) were accessed up to 3 weeks after intrathecal administration.
  
  
  
  Peripheral nerve injury significantly increased the protein level of MyD88 in the DRG and SDH, but had no effect on TRIF. MyD88 was found partly distributed in the nociceptive neurons in the DRGs and the astrocytes and microglia in the SDH. HMGB1 and IL-1β were also found upregulated in nociceptive pathways of CCI rats. Intrathecal application of MIP significantly alleviated mechanical and thermal hyperalgesia in the CCI rats and also reversed CCI-induced upregulation of MyD88 in both DRG and SDH. Further investigation revealed that suppression of MyD88 protein reduced the release of TNF-α and glial activation in the SDH in the CCI rats.
  
  
  
  MyD88-dependent TIR pathway in the DRG and SDH may play a role in CCI-induced neuropathic pain. MyD88 might serve as a potential therapeutic target for neuropathic pain.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Zhiyao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Yikuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Le
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China. garybeijing@163.com.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. machao@ibms.cams.cn.
authors.forename: Chao
authors.identifier: 0000-0003-1346-6961
authors.initials: C
authors.lastname: Ma
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*
chemical_list: C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88
keywords: CCI; Dorsal root ganglion; MyD88; Neuropathic pain; Spinal dorsal horn; TRIF