Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection.
Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO). In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS) in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT). Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test) and allodynia (von Frey hair test). Control animals did not present any alteration (sham-animals). The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 microg in 50 microL), blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30) in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed's lamina X) and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%). Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%), reaching the greatest increase (60%) 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.
Chacur
M
M
Departamento de Fisiologia e Biofísica, Universidade de São Paulo, São Paulo, SP, Brasil. chacurm@icb.usp.br
Matos
R J B
RJ
Alves
A S
AS
Rodrigues
A C
AC
Gutierrez
V
V
Cury
Y
Y
Britto
L R G
LR
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006930:Hyperalgesia / Q000201:enzymology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries*; D012585:Sciatica / Q000201:enzymology* / Q000503:physiopathology
D012333:RNA, Messenger; D052248:Nitric Oxide Synthase Type I