Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injury.
In this study, we examined the relationship between astrocyte activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. In addition, we also examined the effects of pre-emptive treatment with a number of drugs on astrocyte activation and hypersensitivity development in this model. Using immunohistochemistry and immunoblotting, little glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity was detected in the CN of the normal rats. As early as 3 days after CCI, there was a significant increase in GFAP immunoreactivity in the lesion side of CN, and this reached a maximum at 7 days, and was followed by a decline. Counting of GFAP-immunoreactive astrocytes revealed that astrocytic hypertrophy, but not proliferation, contributes to increased GFAP immunoreactivity. Furthermore, microinjection of the glial activation inhibitor, fluorocitrate, into the CN at 3 days after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. These results suggest that median nerve injury-induced astrocytic activation in the CN modulated the development of behavioral hypersensitivity. Animals received MK-801 (glutamate N-methyl-d-aspartate (NMDA) receptor antagonist), clonidine (alpha(2)-adrenoreceptor agonist), tetrodotoxin (TTX, sodium channel blocker) or lidocaine (local anesthetic) 30 min prior to median nerve CCI. Pre-treatment with MK-801, TTX, and 2% lidocaine, but not clonidine, attenuated GFAP immunoreactivity and behavioral hypersensitivity following median nerve injury. In conclusion, suppressing reactions to injury, such as the generation of ectopic discharges and activation of NMDA receptors, can decrease astrocyte activation in the CN and attenuate neuropathic pain sensations.
Chen
Jiann-Jy
JJ
Department of Medical Research, Tao-Yuan General Hospital, Taoyuan, Taiwan Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Br., Yunlin, Taiwan Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan School of Medicine, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan.
Lue
June-Horng
JH
Lin
Lung-Huang
LH
Huang
Chun-Ta
CT
Chiang
Rayleigh Ping-Ying
RP
Chen
Chih-Li
CL
Tsai
Yi-Ju
YJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D008012:Lidocaine; D008297:Male; D020423:Median Neuropathy / Q000188:drug therapy / Q000473:pathology*; D008526:Medulla Oblongata / Q000187:drug effects / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D002951:Citrates; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D026941:Sodium Channel Blockers; C007744:fluorocitrate; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D008012:Lidocaine; D003000:Clonidine