CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy

Huang, Zhenzhen; Li, Dai; Liu, Cuicui; Chen, Yu; Zhu, He-Quan; Zhang, Wenwen; Li, Yongyong; Xin, Wenjun

doi:10.1016/j.bbi.2014.03.014

Cited by 102 publications

(74 citation statements)

References 52 publications

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“…An emerging body of data suggests that paclitaxel also exerts effects on the immune system by stimulating anti-tumor and anti-autoimmunity effects 11,57 . For example, previous reports showed that a higher dose of paclitaxel than used here (cumulative dose 24 mg/kg, 3 × 8mg/kg) also induced a persistent mechanical allodynia that was accompanied by an infiltration of macrophages into the DRG of rats and this was prevented by co-treatment with minocycline during chemotherapy 44,34 , and application of minocycline, an inhibitor of pro-inflammatory cytokine release, prevents mechanical allodynia and IENF loss induced by paclitaxel using the doses of paclitaxel as in this study 7 . Activation of macrophages has been reported to contribute to experimental neuropathic pain states by releasing potent pro-inflammatory mediators, including tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β), MCP-1, nerve growth factor (NGF), nitric oxide (NO) and prostanoids 52 .…”

Section: Discussionmentioning

confidence: 79%

“…The number of total neurons in the same area was counted. The percentages of positive neurons to total neurons were calculated and statistically compared 33 (Huang et al, 2014a)(Huang et al, 2014a)(Huang et al, 2014a). Intraepidermal nerve fiber (IENF) analysis for PGP/GAP43 was performed on images captured utilizing a Zeiss Axio Imager M2 microscope equipped with standard Zeiss objectives (20×) and fluorescent filters for Cy2, alexa488, and DAPI fluorophores, motorized stage control, and a Hamamatsu ORCA Falsh4.0 digital camera attached to a Dell Precision T3600 PC running Win7 and Neurolucida Software to operate the scope system.…”

Section: Methodsmentioning

confidence: 99%

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Dorsal Root Ganglion Infiltration by Macrophages Contributes to Paclitaxel Chemotherapy-Induced Peripheral Neuropathy

Zhang

Carvalho-Barbosa

et al. 2016

The Journal of Pain

256

225

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Chemotherapy-induced peripheral neuropathy (CIPN) is a disruptive and persistent side-effect of cancer treatment with paclitaxel. Recent reports showed that paclitaxel treatment results in the activation of Toll-like receptor 4 (TLR4) signaling and increased expression of monocyte chemotactic protein 1 (MCP-1) in dorsal root ganglion cells. In this study, we sought to determine whether an important consequence of this signaling and also a key step in the CIPN phenotype was the recruitment and infiltration of macrophages into dorsal root ganglia (DRG). Here, we show that macrophage infiltration does indeed occur in a time course that matches the onset of the behavioral CIPN phenotype in Sprague-Dawley rats. Moreover, depletion of macrophages by systemic administration of liposome-encapsulated clodronate (clophosome) partially reversed behavioral signs of paclitaxel-induced CIPN as well as reduced TNFα expression in DRG. Intrathecal injection of MCP-1 neutralizing antibodies reduced paclitaxel-induced macrophage recruitment into the DRG and also blocked the behavioral signs of CIPN. Intrathecal treatment with the TLR4 antagonist LPS-RS blocked mechanical hypersensitivity, reduced MCP-1 expression, and blocked the infiltration of macrophages into the DRG in paclitaxel treated rats. Finally, the inhibition of macrophage infiltration into DRG following paclitaxel treatment with clodronate or LPS-RS prevented the loss of intra-epidermal nerve fibers (IENFs) observed following paclitaxel treatment alone. Taken altogether, these results are the first to indicate a mechanistic link such that activation of TLR4 by paclitaxel leads to increased expression of MCP-1 by DRG neurons resulting in macrophage infiltration to the DRG that express inflammatory cytokines and the combination of these events results in IENF loss and the development of behavioral signs of CIPN.

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Section: Discussionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Dorsal Root Ganglion Infiltration by Macrophages Contributes to Paclitaxel Chemotherapy-Induced Peripheral Neuropathy

Zhang

Carvalho-Barbosa

et al. 2016

The Journal of Pain

256

225

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“…9,34,35 Our recent results that paclitaxel cause apoptosis and macrophage infiltration in the dorsal root ganglion via CX3CL1-suggested expression of CX3CL1 in dorsal root ganglion are involved in the paclitaxel-induced painful peripheral neuropathy. 36 In addition, Elizabeth reported that CX3CL1/CX3R1 signal in the sciatic nerve participated in the vincristine-induced painful peripheral neuropathy. 11 These research suggested that CX3CL1 in the peripheral nervous system might be a critical molecular in chemotherapeutic drug-induced peripheral neuropathy.…”

Section: Pain Medicinementioning

confidence: 99%

“…Recently, our and peer's studies showed that CX3CL1-induced peripheral axonopathy and ganglionopathy is involved in painful neuropathy after chemotherapeutic drug treatment. 10,11 Although it has been well documented that the CX3CL1/ CX3CR1 signaling regulates the interaction between neuronal-microglia in the spinal cord and thereby mediates the development of neuropathic pain, 6,12 involvement of ABSTRACT Background: Up-regulation of CX3CL1 has been revealed to be involved in the neuropathic pain induced by nerve injury. However, whether CX3CL1 participates in the paclitaxel-induced painful peripheral neuropathy remains unknown.…”

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confidence: 99%

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

Huang

Ling

et al. 2015

Anesthesiology

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“…The platinum and the taxane derivatives are used for treatment of several types of cancer as colorectal cancer, lung cancer or ovarian cancer [39,40]. Their chronic administration causes a peripheral neuropathy characterized by hypersensitivity to cold stimuli [41,42]. These models of neuropathic pain are free from inflammatory components and are characterized by specific molecular alteration of the peripheral and central nervous system [35].…”

Section: Discussionmentioning

confidence: 99%

Effects of a water extract of Lepidium meyenii root in different models of persistent pain in rats

Tenci

Mannelli

Maresca

et al. 2017

Zeitschrift Für Naturforschung C

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Lepidium meyenii (Walp.), commonly called maca, is an Andean crop belonging to the Brassicaceae family. Maca hypocotils are habitually consumed as customary food as well as traditional remedies for pathological conditions such as infertility. Moreover, the characterization of maca extracts revealed the presence of compounds that are able to modulate the nervous system. Aimed to evaluate the efficacy of L. meyenii in persistent pain, the present study analyzed the effects of a commercial root extract from maca in different animal models reproducing the most common causes of chronic painful pathologies. A qualitative characterization of this commercial extract by high performance liquid chromatography-mass spectrometry and tandem mass spectrometry analyses allowed us to confirm the presence of some macamides known as bioactive constituents of this root and the absence of the main aromatic glucosinolates. The acute oral administration of maca extract is able to reduce mechanical hypersensitivity and postural unbalance induced by the intra-articular injection of monoiodoacetate and the chronic-constriction injury of the sciatic nerve. Furthermore, L. meyenii extract reverts pain threshold alterations evoked by oxaliplatin and paclitaxel. A good safety profile in mice and rats was shown. In conclusion, the present maca extract could be considered as a therapeutic opportunity to relieve articular and neuropathic pain.

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CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy

Cited by 102 publications

References 52 publications

Dorsal Root Ganglion Infiltration by Macrophages Contributes to Paclitaxel Chemotherapy-Induced Peripheral Neuropathy

Dorsal Root Ganglion Infiltration by Macrophages Contributes to Paclitaxel Chemotherapy-Induced Peripheral Neuropathy

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

Effects of a water extract of Lepidium meyenii root in different models of persistent pain in rats

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