Participation of microglial p38 MAPK in formalin-induced temporomandibular joint nociception in rats

J Orofac Pain. 2012 Spring;26(2):132-41.


Aims: To investigate nociceptive behavior and the immunoreactivity of microglia and phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) following intracisternal administration of SB203580, a p38 MAPK inhibitor, or minocycline, a microglia inhibitor, in rats with temporomandibular joint (TMJ) inflammation.

Methods: The number of nociceptive behavioral responses was recorded for nine successive 5-minute intervals following formalin injections into the left TMJ. SB203580 or minocycline was administered intracisternally 2 hours prior to the formalin injection. Statistical analysis used one-way analysis of variance followed by least significant difference post-hoc analysis.

Results: The intra-articular injection of formalin increased the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn. Most of the p-p38 MAPK co-localized with OX42, a microglial marker, but not with GFAP, an astrocyte marker. Intracisternal injections of SB203580 (0.5, 1, or 5 Μg) attenuated the number of nociceptive behavioral responses and the expression of p-p38 MAPK in the medullary dorsal horn. Intracisternal injections of minocycline (25 or 50 Μg) also attenuated the responses and the expression of OX42 and p-p38 MAPK in the medullary dorsal horn.

Conclusion: These findings suggest that p38 MAPK in microglia plays an important role in the central processing of inflammatory TMJ nociception in rats. The data further indicate that a targeted blockade of the microglial p38 MAPK pathway is a potentially important new treatment strategy for inflammatory TMJ nociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Arthralgia / enzymology*
  • Cisterna Magna / drug effects
  • Endpoint Determination
  • Formaldehyde / administration & dosage
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology
  • Injections, Intra-Articular
  • Male
  • Microglia / drug effects
  • Microglia / enzymology*
  • Minocycline / administration & dosage
  • Minocycline / pharmacology
  • Motor Activity / drug effects
  • Nociception / drug effects*
  • Phosphorylation
  • Posterior Horn Cells / enzymology
  • Protease Inhibitors / administration & dosage
  • Protease Inhibitors / pharmacology
  • Pyridines / administration & dosage
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Temporomandibular Joint / innervation
  • Temporomandibular Joint Disorders / chemically induced
  • Temporomandibular Joint Disorders / enzymology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Imidazoles
  • Protease Inhibitors
  • Pyridines
  • Formaldehyde
  • p38 Mitogen-Activated Protein Kinases
  • Minocycline
  • SB 203580