Inhibition of GAP-43 by propentofylline in a rat model of neuropathic pain.
Neural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. The relation of growth-associated protein-43 (GAP-43), a protein involved in the nerve fiber growth and sprouting, to pain hypersensitivity has been investigated. Glial activation and inflammatory cytokines released by microglia and astrocytes are considered to be involved in the neural sprouting and plasticity. In the present study, the anti-nociception effect of propentofylline, a glial modulating agent, was investigated in a rat chronic constriction injury (CCI) model aiming to explore the role of GAP-43 expression. Our results demonstrated that propentofylline could attenuate the CCI-induced mechanical allodynia and thermal hyperalgesia and inhibit the astrocyte activation and production of IL-1β. GAP-43 expression was also down-regulated by intrathecal propentofylline. These findings suggest that astrocyte activation is involved in the regulation of GAP-43 expression and propentofylline might be used in the treatment of neuropathic pain.
Department of Anesthesiology, Eastern Hepatobiliary Hospital, the Second Military Medical University, No. 225 Changhai Road, Shanghai 200433, China.
Feixiang
F
Wu
Xuerong
X
Miao
Jiaying
J
Chen
Zhiqiang
Z
Liu
Yong
Y
Tao
Weifeng
W
Yu
Yuming
Y
Sun
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology*
D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D014970:Xanthines; C032114:propentofylline
Astrocytes; growth-associated protein-43; interleukin 1β; neuropathic pain