Blockade of microglial activation reduces mechanical allodynia in rats with compression of the trigeminal ganglion

Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):52-9. doi: 10.1016/j.pnpbp.2011.10.007. Epub 2011 Oct 13.

Abstract

The present study investigated the role of microglia and p38 MAPK in the development of mechanical allodynia in rats with compression of the trigeminal ganglion. Male Sprague-Dawley rats weighing 250-260 g were used. Under pentobarbital sodium anesthesia, the animals were mounted onto a stereotaxic frame and given injections of 4% agar solution (10 μL) to compress the trigeminal ganglion. The air-puff thresholds significantly decreased after compression of the trigeminal ganglion. On postoperative day 14, immunoreactivity to both OX-42 and p-p38 MAPK was up-regulated in the medullary dorsal horn as compared to the sham group. P-p38 MAPK was found to be co-localized with OX-42, but not with NeuN, a neuronal cell marker, or with GFAP, an astroglial cell marker. Intracisternal administration of 100 μg of minocycline significantly inhibited both mechanical allodynia and activation of microglia produced by compression of the trigeminal ganglion. Intracisternal administration of 0.1, 1, or 10 μg of SB203580, a p38 MAPK inhibitor, also significantly decreased mechanical allodynia and p38 MAPK activation in the trigeminal ganglion-compressed group. These results suggest that activation of p38 MAPK in the microglia is an important step in the development of mechanical allodynia in rats with compression of the trigeminal ganglion and that the targeted blockade of microglial p38 MAPK pathway is a potentially important new treatment strategy for trigeminal neuralgia-like nociception.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / enzymology
  • Imidazoles / pharmacology
  • Male
  • Microglia* / drug effects
  • Microglia* / enzymology
  • Microglia* / metabolism
  • Nerve Compression Syndromes* / drug therapy
  • Nerve Compression Syndromes* / enzymology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Trigeminal Ganglion* / drug effects
  • Trigeminal Ganglion* / enzymology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / biosynthesis

Substances

  • Imidazoles
  • Pyridines
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580