Spinal CCL2 and microglial activation are involved in paclitaxel-evoked cold hyperalgesia

Up-regulation of CX3CL1 via Nuclear Factor-κB–dependent Histone Acetylation Is Involved in Paclitaxel-induced Peripheral Neuropathy

“…Our results are supported by the recent report that application of paclitaxel up-regulated the chemokine CCL2 expression in the spinal cord. 37 Although it is generally believed that paclitaxel does not penetrate blood-brain barrier, 38,39 low concentrations of paclitaxel can be detected in spinal cord after systemic treatment. 40 It has been reported that paclitaxel can directly impair neuronal activities.…”

Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice

“…TRPV1 (Hara et al, 2013), TRPV4 (AlessandriHaber et al, 2004;Levine and Alessandri-Haber, 2007), TRPA1-and TRPV4-mediated glutathionesensitive mechanisms (Materazzi et al, 2012) might be involved in the development and maintenance of paclitaxel-evoked neuropathic pain, although other molecules, such as sigma-1 receptors (Nieto et al, 2012), cannabinoid receptors (Authier et al, 2009), calcium channels (Authier et al, 2009) and CCL2 chemokines (Pevida et al, 2013), are also considered.…”

Chemotherapy-Induced Peripheral Neuropathy

“…262 Several investigators have also demonstrated an upregulation of chemokine (C-C motif ) ligand 2 (CCL2 or MCP-1) following paclitaxel treatment. 259,263 This increase in chemokine levels was shown to have functional importance, since intrathecal inhibition of the receptor for CCL2, the C-C chemokine receptor type 2 (CCR2), reverses mechanical allodynia, and the degeneration of IENF induced by paclitaxel administration. 263 The signaling pathways by which paclitaxel upregulates CCL2 levels have not been elucidated, but CCL2 is enhanced primarily in small-diameter sensory neurons within the DRG and in astrocytes of the dorsal horn.…”

“…This function is apparent in the dorsal horn of the spinal cord, where a paclitaxel-induced upregulation of CCL2 activates microglia, reversible by intrathecal application of an anti-CCL2 antibody. 259,263 What remains unclear, however, is how paclitaxel-induced activation of the CCL2/CCR2 pathway, which occurs in the entire dorsal column regardless of axonal length, 263 can initiate neuronal sensitivity in a "stocking and glove" distribution. Further investigations into possible interactions between inflammation and axonal damage, both induced by chemotherapeutic treatment, to elicit symptoms of CIPN might uncover additional therapeutic targets to prevent or treat the neuropathy.…”