Contribution of Microglia and Astrocytes to the Central Sensitization, Inflammatory and Neuropathic Pain in the Juvenile Rat

Molecular Pain - Tập 8 - 2012
Hiroshi Ikeda1, Takaki Kiritoshi1, Kazuyuki Murase1
1Department of Human and Artificial Intelligence Systems, Graduate School of Engineering; Research and Education Program for Life Science, University of Fukui, 3-9-1 Bunkyo, Fukui, 910-8507, Japan

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1016/j.tins.2003.09.017

10.1007/978-1-4419-0226-9_10

10.1016/j.neuron.2009.09.033

10.1038/nrn2533

10.1038/nn1992

10.1016/j.pain.2005.02.009

10.1016/j.ejphar.2009.09.030

10.1124/jpet.103.052407

10.1111/j.1471-4159.2010.06946.x

10.1016/j.brainresbull.2009.01.009

10.1016/j.brainresrev.2008.12.011

10.1002/glia.20623

10.1523/JNEUROSCI.3512-08.2008

10.1016/j.tins.2004.12.002

10.1002/glia.20648

10.1016/j.brainresrev.2009.11.003

10.1016/j.pharmthera.2005.07.001

10.1016/j.pharmthera.2010.01.002

10.1038/nature04223

10.1523/JNEUROSCI.5714-08.2009

10.1016/S0006-8993(98)00928-7

10.1523/JNEUROSCI.2608-04.2004

10.1111/j.1460-9568.2007.05386.x

10.1016/j.jpain.2004.06.006

Charles A, 1998, Intercellular calcium waves in glia. Glia, 24, 39

10.1523/JNEUROSCI.23-17-06728.2003

10.1111/j.1460-9568.2004.03514.x

10.1016/j.ejpain.2006.02.003

10.1016/S0304-3959(02)00097-0

10.1016/j.pain.2009.11.017

10.1126/science.1080659

10.1126/science.1127233

10.1097/00001756-200210070-00017

10.1016/j.neuropharm.2006.05.024

10.1523/JNEUROSCI.23-07-02517.2003

10.1523/JNEUROSCI.5290-05.2006

10.1016/0166-2236(96)10046-1

10.2174/1876386301003010123

10.1007/s12035-007-0033-y

10.1111/j.1460-9568.2005.04451.x

10.1097/00000542-200602000-00021

10.1016/j.bbi.2006.10.007

10.1016/0165-0270(94)90144-9

Thông tin
Thông tin xuất bản

Molecular Pain

Tập 8

Thông tin tác giả