PMID- 26820818
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20170406
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 30
IP  - 3
DP  - 2016 Jun
TI  - Analgesic effects evoked by a CCR2 antagonist or an anti-CCL2 antibody in 
      inflamed mice.
PG  - 235-47
LID - 10.1111/fcp.12182 [doi]
AB  - Chemokine CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), is a 
      molecule that in addition to its well-established role in chemotaxis can also act 
      as nociceptor sensitizer. The upregulation of this chemokine in inflamed tissues 
      could suggest its involvement in inflammatory hypernociception. Thus, we have 
      measured CCL2 levels in mice with acute or chronic inflammation due to the 
      intraplantar (i.pl.) injection of carrageenan or complete Freund's adjuvant 
      (CFA), respectively, and we have studied whether inflammatory hyperalgesia or 
      allodynia could be attenuated by blocking CCR2 receptors or neutralizing CCL2 
      with an anti-CCL2 antibody. A remarkable increase in CCL2 concentration was 
      detected by ELISA in paw homogenates coming from carrageenan- or CFA-inflamed 
      mice, being its expression mainly localized in macrophages, as shown by 
      immunohistochemical assays. The s.c. (0.3-3 mg/kg) or i.pl. (0.3-3 mug) 
      administration of the CCR2 antagonist, RS 504393, dose dependently inhibited 
      thermal hyperalgesia measured in acutely or chronically inflamed mice, whereas 
      s.c. administration of this drug did not reduce inflammatory mechanical 
      allodynia. Furthermore, the inhibition of inflammatory hyperalgesia after the 
      administration of an anti-CCL2 antibody (0.1-1 mug; i.pl.) suggests that CCL2 
      could be the endogenous chemokine responsible for CCR2-mediated hyperalgesic 
      effects. Besides, the acute administration of the highest antihyperalgesic dose 
      of RS 504393 assayed did not reduce paw tumefaction or modify the presence of 
      inflammatory cells. These results indicate that the blockade of the CCL2/CCR2 
      system can counteract inflammatory hyperalgesia, being this antinociceptive 
      effect unrelated to a decrease in the inflammatory reaction.
CI  - (c) 2016 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Llorian-Salvador, Maria
AU  - Llorian-Salvador M
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Pevida, Marta
AU  - Pevida M
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Gonzalez-Rodriguez, Sara
AU  - Gonzalez-Rodriguez S
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Lastra, Ana
AU  - Lastra A
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Fernandez-Garcia, Maria-Teresa
AU  - Fernandez-Garcia MT
AD  - Unidad de Histopatologia Molecular en Modelos Animales de Cancer, IUOPA, 
      Universidad de Oviedo, C/Julian Claveria 6, 33006, Oviedo, Spain.
FAU - Hidalgo, Agustin
AU  - Hidalgo A
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Baamonde, Ana
AU  - Baamonde A
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
FAU - Menendez, Luis
AU  - Menendez L
AD  - Facultad de Medicina, Laboratorio de Farmacologia, Instituto Universitario de 
      Oncologia del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julian 
      Claveria 6, 33006, Oviedo, Spain.
LA  - eng
PT  - Journal Article
DEP - 20160217
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Analgesics)
RN  - 0 (Benzoxazines)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RS 504393)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Spiro Compounds)
SB  - IM
MH  - Analgesics/pharmacology/*therapeutic use
MH  - Animals
MH  - Benzoxazines/pharmacology/*therapeutic use
MH  - Chemokine CCL2/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Hyperalgesia/*drug therapy/metabolism
MH  - Inflammation/drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Pain Threshold/drug effects/physiology
MH  - Receptors, CCR2/*antagonists & inhibitors/metabolism
MH  - Spiro Compounds/pharmacology/*therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - CCL2
OT  - CCR2
OT  - carrageenan
OT  - chemokines
OT  - complete Freund's adjuvant
OT  - inflammation
OT  - mouse
EDAT- 2016/01/29 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/01/29 06:00
PHST- 2015/07/24 00:00 [received]
PHST- 2015/12/22 00:00 [revised]
PHST- 2016/01/25 00:00 [accepted]
PHST- 2016/01/29 06:00 [entrez]
PHST- 2016/01/29 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
AID - 10.1111/fcp.12182 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2016 Jun;30(3):235-47. doi: 10.1111/fcp.12182. Epub 2016 
      Feb 17.