Paclitaxel induces acute pain via directly activating toll like receptor 4

Molecular Pain

Han-Rong Weng²  Michael G Bartlett²  Pei Li²  Mei Gao²  Ruchi Yadav²  Dylan W Maixner²  Xisheng Yan¹ 

[1] Department of Cardiovascular Medicine, The Third Hospital of Wuhan, Wuhan 430060, Hubei Province, China;Department of Pharmaceutical and Biomedical Sciences, The University of Georgia College of Pharmacy, 250 West Green Street, Athens 30602, GA, USA

关键词: Burrowing behavior;    EPSC;    Neuroinflammation;    DRG;    Nociception;    Taxol;   

Others  :  1159803
DOI  :  10.1186/s12990-015-0005-6

 received in 2014-11-17, accepted in 2015-02-10,  发布年份 2015

【 摘 要 】

Paclitaxel, a powerful anti-neoplastic drug, often causes pathological pain, which significantly reduces the quality of life in patients. Paclitaxel-induced pain includes pain that occurs immediately after paclitaxel treatment (paclitaxel-associated acute pain syndrome, P-APS) and pain that persists for weeks to years after cessation of paclitaxel treatment (paclitaxel induced chronic neuropathic pain). Mechanisms underlying P-APS remain unknown. In this study, we found that paclitaxel causes acute pain in rodents in a dose-dependent manner. The paclitaxel-induced acute pain occurs within 2 hrs after a single intravenous injection of paclitaxel. This is accompanied by low levels of paclitaxel penetrating into the cerebral spinal fluid and spinal dorsal horn. We demonstrated that an intrathecal injection of paclitaxel induces mechanical allodynia in a dose-dependent manner. Paclitaxel causes activation of toll like receptor 4 (TLR4) in the spinal dorsal horn and dorsal root ganglions. Through activating TLR4, paclitaxel increases glutamatergic synaptic activities and reduces glial glutamate transporter activities in the dorsal horn. Activations of TLR4 are necessary in the genesis of paclitaxel-induced acute pain. The cellular and molecular signaling pathways revealed in this study could provide rationales for the development of analgesics and management strategies for P-APS in patients.

【 授权许可】

   
2015 Yan et al.; licensee BioMed Central.

【 图 表 】

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