PMID- 23726937
OWN - NLM
STAT- MEDLINE
DCOM- 20140508
LR  - 20220408
IS  - 1528-8447 (Electronic)
IS  - 1526-5900 (Print)
IS  - 1526-5900 (Linking)
VI  - 14
IP  - 10
DP  - 2013 Oct
TI  - Induction of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 in 
      primary sensory neurons contributes to paclitaxel-induced peripheral neuropathy.
PG  - 1031-44
LID - S1526-5900(13)00961-9 [pii]
LID - 10.1016/j.jpain.2013.03.012 [doi]
AB  - The use of paclitaxel (Taxol), a microtubule stabilizer, for cancer treatment is 
      often limited by its associated peripheral neuropathy (chemotherapy-induced 
      peripheral neuropathy [CIPN]), which predominantly results in sensory 
      dysfunction, including chronic pain. Here we show that paclitaxel CIPN was 
      associated with induction of chemokine monocyte chemoattractant protein-1 (MCP-1) 
      and its cognate receptor CCR2 in primary sensory neurons of dorsal root ganglia. 
      Immunostaining revealed that MCP-1 was mainly expressed in small nociceptive 
      neurons whereas CCR2 was expressed in large and medium-sized myelinated neurons. 
      Direct application of MCP-1 consistently induced intracellular calcium increases 
      in dorsal root ganglia large and medium-sized neurons but not in small neurons 
      mainly dissociated from paclitaxel-treated but not vehicle-treated animals. 
      Paclitaxel also induced increased expression of MCP-1 in spinal astrocytes, but 
      no CCR2 signal was detected in the spinal cord. Local blockade of MCP-1/CCR2 
      signaling by anti-MCP-1 antibody or CCR2 antisense oligodeoxynucleotides 
      significantly attenuated paclitaxel CIPN phenotypes including mechanical 
      hypersensitivity and loss of intraepidermal nerve fibers in hindpaw glabrous 
      skin. These results suggest that activation of paracrine MCP-1/CCR2 signaling 
      between dorsal root ganglion neurons plays a critical role in the development of 
      paclitaxel CIPN, and targeting MCP-1/CCR2 signaling could be a novel therapeutic 
      approach. PERSPECTIVE: CIPN is a severe side effect accompanying paclitaxel 
      chemotherapy and lacks effective treatments. The current study suggests that 
      blocking MCP-1/CCR2 signaling could be a new therapeutic strategy to prevent or 
      reverse paclitaxel CIPN. This preclinical evidence encourages future clinical 
      evaluation of this strategy.
CI  - Copyright (c) 2013 American Pain Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Zhang, Haijun
AU  - Zhang H
AD  - Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. 
      Anderson Cancer Center, Houston, Texas. Electronic address: 
      haijun.zhang@mdanderson.org.
FAU - Boyette-Davis, Jessica A
AU  - Boyette-Davis JA
FAU - Kosturakis, Alyssa K
AU  - Kosturakis AK
FAU - Li, Yan
AU  - Li Y
FAU - Yoon, Seo-Yeon
AU  - Yoon SY
FAU - Walters, Edgar T
AU  - Walters ET
FAU - Dougherty, Patrick M
AU  - Dougherty PM
LA  - eng
GR  - R01 NS046606/NS/NINDS NIH HHS/United States
GR  - P01 CA124787/CA/NCI NIH HHS/United States
GR  - CA12487/CA/NCI NIH HHS/United States
GR  - NS046606/NS/NINDS NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130531
PL  - United States
TA  - J Pain
JT  - The journal of pain
JID - 100898657
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - P88XT4IS4D (Paclitaxel)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*adverse effects
MH  - Calcium/metabolism
MH  - Chemokine CCL2/*drug effects
MH  - Female
MH  - Ganglia, Spinal/drug effects/pathology
MH  - Immunohistochemistry
MH  - Injections, Spinal
MH  - Paclitaxel/*adverse effects
MH  - Pain Threshold/drug effects
MH  - Peripheral Nervous System Diseases/*chemically induced/pathology
MH  - Physical Stimulation
MH  - Posterior Horn Cells/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, CCR2/*drug effects
MH  - Sensory Receptor Cells/*drug effects
PMC - PMC3791166
MID - NIHMS469592
OTO - NOTNLM
OT  - CCR2
OT  - MCP-1
OT  - Paclitaxel
OT  - dorsal root ganglion
OT  - neuropathy
EDAT- 2013/06/04 06:00
MHDA- 2014/05/09 06:00
PMCR- 2014/10/01
CRDT- 2013/06/04 06:00
PHST- 2012/09/23 00:00 [received]
PHST- 2013/01/15 00:00 [revised]
PHST- 2013/03/05 00:00 [accepted]
PHST- 2013/06/04 06:00 [entrez]
PHST- 2013/06/04 06:00 [pubmed]
PHST- 2014/05/09 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - S1526-5900(13)00961-9 [pii]
AID - 10.1016/j.jpain.2013.03.012 [doi]
PST - ppublish
SO  - J Pain. 2013 Oct;14(10):1031-44. doi: 10.1016/j.jpain.2013.03.012. Epub 2013 May 
      31.