Neuropathic Pain Caused by Vincristine

Experimental models of neuropathic pain caused by repeated systemic treatment of vincristine were established to clarify therapeutic targets and potential therapeutic agents (Authier etal, 1999 Tanner etal, 1998). Studies characterized neuropathic pain caused by vincristine, and indicated that the involvement of inflammatory cytokines was similar to neuropathic pain induced by nerve injury (Kiguchi et al., 2008a,b). 

We focus on the aspects of neuropathic pain caused by vincristine. We refer to the roles of inflammatory cytokines, which may be critical in the development and maintenance of neuropathic pain. 

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INVOLVEMENT OF INFLAMMATORY MEDIATORS IN NEUROPATHIC PAIN CAUSED BY VINCRISTINE... 

Elucidation of the mechanism of neuropathic pain caused by vincristine is required because long-term treatment with this anticancer agent often causes neuropathic pain. We refer to the involvement of inflammatory mediators in vincristine-induced neuropathic pain in this review. 

Immune-modulating agents that prevent activation of immune cells and/or the inhibitory agents of inflammatory cytokines could prevent the neuropathic pain caused by vincristine. These agents could increase the tolerability of vincristine when used for the treatment of leukemia and lymphoma. 

Vincristine, a vinca-alkaloid, prevents proliferation of tumor cells through the inhibition of tubulin polymerization. Vincristine is used as an anticancer agent for leukemia and lymphoma (Himes etal, 1976 Owellen etal., 1976). Clinical use of vincristine is often limited by its adverse effects, which include painful peripheral neuropathy (i.e., neuropathic pain) (Casey et al., 1973 Sandler et al., 1969). Elucidation of the detailed mechanism of neuropathic pain caused by vincristine is needed to improve quality-of-life for patients, and to make vincristine more tolerable for cancer treatment. 

Fig. 1. Peripheral and central mechanism of neuropathic pain caused by vincristine. The upper diagram shows the effect of vincristine on the peripheral nervous system (comprising Schwann cells and the dorsal root ganglion (DRG)) and the involvement of interleukin (IL)-6 derived from infiltrating macrophages in neuropathic pain caused by vincristine. The lower diagram shows the effect of vincristine on the central nervous system, and the involvement of tumor necrosis factor-a (TNF-a) derived from activated microglia and astrocytes in neuropathic pain caused by vincristine.

The detailed molecular mechanism of neuropathic pain caused by repeated systemic injection of vincristine is poorly understood. In general, systemically injected vincristine poorly penetrates into the CNS because of the blood—brain barrier (BBB) (Calabresi and Parks, 1985). It is thought that vincristine may act on... 

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