Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord.

Abstract

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.

• Authors: Younglim Lee, Madhavi Pai, Jill-Desiree Brederson, Denise Wilcox, Gin Hsieh, Michael F Jarvis, Robert S Bitner
• Journal: Molecular pain (Mol Pain) Vol. 7 Pg. 39 (May 20 2011) ISSN: 1744-8069 [Electronic] United States
• PMID: 21599960 (Publication Type: Journal Article)

Chemical References

• Flavonoids
• Iodoacetates
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 1
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Behavior, Animal (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flavonoids (pharmacology)
• Hyperalgesia (complications, pathology)
• Immunohistochemistry
• Injections, Intra-Articular
• Iodoacetates (administration & dosage)
• Joints (drug effects, pathology)
• MAP Kinase Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Neuroglia (enzymology, pathology)
• Nociceptors (drug effects, metabolism, pathology)
• Osteoarthritis (complications, enzymology, pathology)
• Pain (chemically induced, complications, enzymology, pathology)
• Phenotype
• Phosphorylation (drug effects)
• Posterior Horn Cells (drug effects, enzymology, pathology)
• Rats
• Spinal Cord (drug effects, enzymology, pathology)
• p38 Mitogen-Activated Protein Kinases (metabolism)