Differential activation of spinal microglial and astroglial cells in a mouse model of peripheral neuropathic pain.
The pharmacological attenuation of glial activation represents a novel approach for controlling neuropathic pain, but the role of microglial and astroglial cells is not well established. To better understand the potential role of two types of glial cells, microglia and astrocytes, in the pathogenesis of neuropathic pain, we examined markers associated with them by quantitative RT-PCR, western blot and immunohistochemical analyses in the dorsal horn of the lumbar spinal cord 7days after chronic constriction injury (CCI) to the sciatic nerve in mice. The mRNA and protein of microglial cells were labeled with C1q and OX42(CD11b/c), respectively. The mRNA and protein of astrocytes were labeled with GFAP. The RT-PCR results indicated an increase in C1q mRNA that was more pronounced than the increased expression of GFAP mRNA ipsilateral to the injury in the dorsal spinal cord. Similarly, western blot and immunohistochemical analyses demonstrated an ipsilateral upregulation of OX42-positive cells (72 and 20%, respectively) and no or little (8% upregulation) change in GFAP-positive cells in the ipsilateral dorsal lumbar spinal cord. We also found that chronic intraperitoneal injection of the minocycline (microglial inhibitor) and pentoxifylline (cytokine inhibitor) attenuated CCI-induced activation of microglia, and both, but not fluorocitrate (astroglial inhibitor), diminished neuropathic pain symptoms and tactile and cold sensitivity. Our findings indicate that spinal microglia are more activated than astrocytes in peripheral injury-induced neuropathic pain. These findings implicate a glial regulation of the pain response and suggest that pharmacologically targeting microglia could effectively prevent clinical pain syndromes in programmed and/or anticipated injury.
Mika
Joanna
J
Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Osikowicz
Maria
M
Rojewska
Ewelina
E
Korostynski
Michal
M
Wawrzczak-Bargiela
Agnieszka
A
Przewlocki
Ryszard
R
Przewlocka
Barbara
B
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002951:Citrates / Q000627:therapeutic use; D015922:Complement C1q / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000502:physiology*; D008911:Minocycline / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects*; D009928:Organ Specificity; D010147:Pain Measurement; D010431:Pentoxifylline / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D013116:Spinal Cord / Q000166:cytology*
D000700:Analgesics; D015415:Biomarkers; D002951:Citrates; D005904:Glial Fibrillary Acidic Protein; D016177:Macrophage-1 Antigen; D010726:Phosphodiesterase Inhibitors; C007744:fluorocitrate; D015922:Complement C1q; D008911:Minocycline; D010431:Pentoxifylline