title: Peritoneal administration of Met-RANTES attenuates inflammatory and nociceptive responses in a murine neuropathic pain model.
abstract: The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNFα, IL-1β, IL-6, and IFNγ) protein secretion, and enkephalin, β-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model.
  
  
  CONCLUSIONS
  The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model.
authors.affiliation: Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou,Taiwan, ROC.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Liou
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Mao
authors.forename: Daniel
authors.initials: D
authors.lastname: Ching-Wah Sum
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: Lai
authors.forename: Jui-Chin
authors.initials: JC
authors.lastname: Li
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001522:Behavior, Animal / Q000187:drug effects; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004723:Endorphins / Q000096:biosynthesis; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007378:Interleukins / Q000096:biosynthesis; D017254:Leukemic Infiltration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy* / Q000523:psychology; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D016207:Cytokines; D004723:Endorphins; D007378:Interleukins; C108335:RANTES, Met-; D054389:Receptors, CCR1