title: 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.
  
  
  CONCLUSIONS
  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: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. younglim.lee@abbott.com
authors: Younglim
authors: Y
authors: Lee
authors: Madhavi
authors: M
authors: Pai
authors: Jill-Desiree
authors: JD
authors: Brederson
authors: Denise
authors: D
authors: Wilcox
authors: Gin
authors: G
authors: Hsieh
authors: Michael F
authors: MF
authors: Jarvis
authors: Robert S
authors: RS
authors: Bitner
references: Osteoarthritis Cartilage. 2003 Nov;11(11):821-30
references: 14609535
references: Expert Opin Investig Drugs. 2008 May;17(5):619-40
references: 18447590
references: Brain Res Rev. 2009 Apr;60(1):135-48
references: 19150373
references: Pain. 2005 Aug;116(3):411-419
references: 15979799
references: Neurosci Lett. 2004 Nov 11;370(2-3):236-40
references: 15488329
references: Baillieres Best Pract Res Clin Rheumatol. 2000 Dec;14(4):797-811
references: 11092803
references: Pain. 2004 Nov;112(1-2):83-93
references: 15494188
references: Arthritis Res Ther. 2007;9(1):R14
references: 17284318
references: FASEB J. 1995 Jun;9(9):726-35
references: 7601337
references: Pain. 2002 Sep;99(1-2):175-84
references: 12237195
references: Ann N Y Acad Sci. 2002 Jun;966:343-54
references: 12114291
references: Pain. 1993 Oct;55(1):5-54
references: 8278210
references: Neurochem Res. 2008 Oct;33(10):1970-8
references: 18427980
references: Neurosci Lett. 1983 Apr 11;36(2):139-43
references: 6306518
references: Arthritis Rheum. 1997 Sep;40(9):1670-9
references: 9324022
references: Physiol Behav. 1976 Dec;17(6):1031-6
references: 14677603
references: Arthritis Rheum. 1998 May;41(5):778-99
references: 9588729
references: Eur J Pharmacol. 2009 Jun 24;613(1-3):39-45
references: 19376109
references: J Neurosci. 2003 May 15;23(10):4017-22
references: 12764087
references: Trends Neurosci. 1999 Mar;22(3):122-7
references: 10199637
references: J Neurosci Methods. 1994 Jul;53(1):55-63
references: 7990513
references: Pain. 2010 Feb;148(2):309-319
references: 20022176
references: J Vet Med Sci. 2003 Nov;65(11):1195-9
references: 14665748
references: J Musculoskelet Neuronal Interact. 2008 Oct-Dec;8(4):303-6
references: 19147949
references: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1322-9
references: 17618720
references: Pain. 2005 Mar;114(1-2):149-59
references: 15733640
references: Brain Res. 2006 Sep 7;1108(1):28-38
references: 16863646
references: Pain. 2007 Apr;128(3):272-282
references: 17276007
references: Br J Pharmacol. 2003 Mar;138(5):751-6
references: 12642375
references: Annu Rev Pharmacol Toxicol. 1980;20:441-62
references: 7387124
references: J Musculoskelet Neuronal Interact. 2001 Jun;1(4):363-76
references: 15758487
references: Physiol Rev. 1999 Jan;79(1):143-80
references: 9922370
references: Arthritis Res Ther. 2009;11(3):227
references: 19519925
references: Glia. 2004 Jan 1;45(1):89-95
references: 14648549