Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain.
A mouse model of neuropathic pain consisting of chronic constriction injury (CCI) of the sciatic nerve was used to examine the involvement of reactive oxygen species (ROS) in early spinal cord pro-apoptotic gene over-expression during the development of neuropathic pain. RT-PCR analysis showed increased expression of bax, apoptotic protease-activating factor-1 (apaf-1), and caspase-9 in the dorsal horn spinal cord 3 days after chronic constriction injury of sciatic nerve. Consistent with biomolecular data, a marked increase in TUNEL-positive and caspase-3 active form was observed by 3 days CCI. Administration of phenyl-N-tert-butylnitrone (PBN), a potent ROS scavenger, reduced the development of thermal hyperalgesia and mechanical allodynia at 1 and 3 days post-CCI, and decreased the mRNA levels of bax, apaf-1, and caspase-9. PBN also reduced apoptotic and active Caspase-3 positive profiles in the superficial laminae (I-III) of the spinal cord. This study provides evidence that PBN inhibits over-expression of pro-apoptotic genes and neural apoptosis in the spinal cord dorsal horn induced by early-CCI of the sciatic nerve. These findings suggest that ROS regulate expression of some apoptotic genes which might play a role in the onset of neuropathic pain.
Siniscalco
Dario
D
Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, via S. Maria di Costantinopoli, 16, 80138 Napoli, Italy.
Fuccio
Carlo
C
Giordano
Catia
C
Ferraraccio
Franca
F
Palazzo
Enza
E
Luongo
Livio
L
Rossi
Francesco
F
Roth
Kevin A
KA
Maione
Sabatino
S
de Novellis
Vito
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020426:Sciatic Neuropathy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C029217:phenyl-N-tert-butylnitrone; D012313:RNA