Spinal mechanisms underlying acute pain syndrome induced by paclitaxel

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Han-Rong Weng

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Paclitaxel (taxol) is a first-line chemotherapy-drug used to treat many types of cancers. Neuropathic pain and sensory dysfunction are the major toxicities that are dose-limiting and significantly reduce the quality of life in patients. Pathological pain induced by taxol in patients includes pain that occurs immediately after taxol treatment (the so called paclitaxel-associated acute pain syndrome, P-APS), and pain that persists for weeks to years after cessation of paclitaxel treatment (the so called paclitaxel induced chronic neuropathic pain). There is no proven standard of care for the prevention or treatment of P-APS. In this study, we found that paclitaxel causes acute pain in rodents. The paclitaxel-induced acute pain occurs within 2 hrs after a single intravenous injection of paclitaxel (2 mg/kg). This is accompanied with low levels of paclitaxel penetrating into the cerebral spinal fluid and spinal dorsal horn. Paclitaxel directly acts on microglial TLR4 and increases Ca2+ levels in microglia in the spinal dorsal horn, which in turn activates astrocytes through releasing IL-1βIL-1βincreases glutamatergic synaptic activities and reduces glial glutamate transporter activities in the spinal dorsal horn. Activations of TLR4 and IL-1β receptors are critically implicated in the genesis of the paclitaxel-induced acute pain behaviors. The cellular and molecular signaling pathways revealed in this study could provide rationales for the development of analgesics and management of P-APS in patients.