title: CC-chemokine ligand 4/macrophage inflammatory protein-1β participates in the induction of neuropathic pain after peripheral nerve injury.
abstract: BACKGROUND
  Neuropathic pain is caused by neural damage or dysfunction and neuropathic pain-related symptoms are resistant to conventional analgesics. Neuroinflammation due to the cytokine-chemokine network may play a pivotal role in neuropathic pain. We demonstrate that macrophage inflammatory protein-1β (MIP-1β) participates in neuropathic pain.
  
  
  METHODS
  Mice received partial sciatic nerve ligation (PSL), and tactile allodynia and thermal hyperalgesia were assessed by von Frey test and Hargreaves test, respectively. Agents were administered into the region surrounding the sciatic nerve (SCN).
  
  
  RESULTS
  Using reverse transcription polymerase chain reaction, the mRNA expressions of MIP-1β and its receptor (CC-chemokine receptor 5; CCR5) in the injured SCN were up-regulated after PSL. MIP-1β immunoreactivity was localized in macrophages and Schwann cells and increased in the injured SCN on day 1. PSL-induced tactile allodynia on days 4 to 7 was prevented by the administration of MIP-1β neutralizing antibody (anti-MIP-1β; on days 0, 3 and 6). PSL-induced up-regulations of inflammatory cytokine-chemokine mRNAs in the injured SCN were suppressed with anti-MIP-1β treatment on day 7. Administration of CCR5 antagonist, D-ala-peptide T-amide (on days 0, 3 and 6) prevented tactile allodynia and thermal hyperalgesia on days 4 to 14. Single administration of recombinant mouse MIP-1β (rmMIP-1β) elicited tactile allodynia. Moreover, rmMIP-1β increased the mRNA expression of inflammatory mediators in the SCN on day 1 after administration.
  
  
  CONCLUSIONS
  These results suggest that MIP-1β is a novel key mediator, and the peripheral MIP-1β-CCR5 axis contributes to neuropathic pain. Therefore, investigation of this cascade might be a validated approach for the elucidation of neuropathic pain mechanisms.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Saika
authors.forename: N
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: S
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4 / Q000378:metabolism* / Q000494:pharmacology; D006930:Hyperalgesia / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009437:Neuralgia / Q000378:metabolism; D015717:Peptide T / Q000494:pharmacology; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D019713:Receptors, CCR5 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D020426:Sciatic Neuropathy / Q000209:etiology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D012333:RNA, Messenger; D019713:Receptors, CCR5; D015717:Peptide T; C055175:peptide T amide