PMID- 21599960
OWN - NLM
STAT- MEDLINE
DCOM- 20110912
LR  - 20211020
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 7
DP  - 2011 May 20
TI  - Monosodium iodoacetate-induced joint pain is associated with increased 
      phosphorylation of mitogen activated protein kinases in the rat spinal cord.
PG  - 39
LID - 10.1186/1744-8069-7-39 [doi]
AB  - BACKGROUND: Intra-articular injection of monosodium iodoacetate (MIA) in the knee 
      joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration 
      and subsequent nociceptive behavior that has been described as a model of 
      osteoarthritis (OA) pain. Central sensitization through activation of mitogen 
      activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in 
      chronic pain. In the present studies, induction of central sensitization as 
      indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 
      phosphorylation, was assessed in the MIA-OA model. RESULTS: Behaviorally, 
      MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks 
      post-MIA treatment. In the same animals, activation of phospho ERK1/2 was 
      gradually increased, reaching a significant level at post injection week 3. 
      Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection 
      week 1 and decreased, but remained elevated, thereafter. Double labeling from 
      3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In 
      contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but 
      not astrocytes. Additionally, there was increased ipsilateral expression of 
      microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased 
      MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to 
      the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal 
      injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force 
      and pERK1/2 induction in MIA-OA rats. CONCLUSION: Results of these studies 
      support the role of MAPK activation in the progression and maintenance of central 
      sensitization in the MIA-OA experimental pain model.
FAU - Lee, Younglim
AU  - Lee Y
AD  - Neuroscience Research, Global Pharmaceutical Research and Development, Abbott 
      Laboratories, Abbott Park, IL 60064, USA. younglim.lee@abbott.com
FAU - Pai, Madhavi
AU  - Pai M
FAU - Brederson, Jill-Desiree
AU  - Brederson JD
FAU - Wilcox, Denise
AU  - Wilcox D
FAU - Hsieh, Gin
AU  - Hsieh G
FAU - Jarvis, Michael F
AU  - Jarvis MF
FAU - Bitner, Robert S
AU  - Bitner RS
LA  - eng
PT  - Journal Article
DEP - 20110520
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Flavonoids)
RN  - 0 (Iodoacetates)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Flavonoids/pharmacology
MH  - Hyperalgesia/complications/pathology
MH  - Immunohistochemistry
MH  - Injections, Intra-Articular
MH  - Iodoacetates/administration & dosage
MH  - Joints/drug effects/*pathology
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neuroglia/enzymology/pathology
MH  - Nociceptors/drug effects/metabolism/pathology
MH  - Osteoarthritis/complications/enzymology/pathology
MH  - Pain/chemically induced/complications/*enzymology/*pathology
MH  - Phenotype
MH  - Phosphorylation/drug effects
MH  - Posterior Horn Cells/drug effects/enzymology/pathology
MH  - Rats
MH  - Spinal Cord/drug effects/*enzymology/*pathology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3120677
EDAT- 2011/05/24 06:00
MHDA- 2011/09/13 06:00
PMCR- 2011/05/20
CRDT- 2011/05/24 06:00
PHST- 2010/12/14 00:00 [received]
PHST- 2011/05/20 00:00 [accepted]
PHST- 2011/05/24 06:00 [entrez]
PHST- 2011/05/24 06:00 [pubmed]
PHST- 2011/09/13 06:00 [medline]
PHST- 2011/05/20 00:00 [pmc-release]
AID - 1744-8069-7-39 [pii]
AID - 10.1186/1744-8069-7-39 [doi]
PST - epublish
SO  - Mol Pain. 2011 May 20;7:39. doi: 10.1186/1744-8069-7-39.