Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat.

Abstract

BACKGROUND:

The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain.

RESULTS:

In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP.

CONCLUSIONS:

These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

• Authors: Hiroshi Ikeda, Takaki Kiritoshi, Kazuyuki Murase
• Journal: Molecular pain (Mol Pain) Vol. 8 Pg. 43 (Jun 15 2012) ISSN: 1744-8069 [Electronic] United States
• PMID: 22703840 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium

Topics

• Animals
• Astrocytes (metabolism)
• Calcium (metabolism)
• Central Nervous System Sensitization
• Female
• Ganglia, Spinal (metabolism)
• Inflammation (metabolism)
• Male
• Microglia (metabolism)
• Neuralgia (metabolism)
• Rats
• Rats, Wistar
• Spinal Nerve Roots (metabolism)