Effect of intrathecal NG-nitro-L-arginine methyl ester administration on Fos expression in the spinal dorsal horn in rats following sciatic nerve ligation.
BACKGROUND
In the available literature, the pro- or antinociceptive role of nitric oxide (NO) is warmly disputed. As a marker of neuronal activation of the central nervous system, Fos expression has been widely used to assess the change in central neuronal activity evoked by peripheral input. In this study, we examined the effect of intrathecal L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, on nociceptive behavior and spinal Fos expression in rats following chronic constriction injury (CCI) of sciatic nerve, a model of neuropathic pain similar to that observed in clinical setting.


METHODS
Eighty adult male SD rats showing no neurological deficiency a week after intrathecal catheterization were used in this study. L-NAME 250 microg of 10 microl (an equivalent or 0.9% saline) was injected intrathecally 15 min prior to CCI or sham operation. In addition to examination of thermal hyperalgesia by paw withdrawal latency (PWL), measurement of Fos protein staining neurons in the lumbar spinal cord using an immunohistochemistry technique were made at 1, 3, 7 and 14 days after operation.


RESULTS
As compared with untreated animals, both CCI and sham operations evoked an early and long-term Fos expression, whereas a significant decrease in PWL was demonstrated only in rats receiving CCI. On days 3, 7 and 14 after CCI, the number of FLI neurons in the spinal dorsal horn ipsilateral to the injury decreased by 54%, 57% and 43%, respectively, in CCI-L-NAME group when compared with CCI-saline group, corresponding to the significant attenuation of thermal hyperalgesia. However, intrathecal L-NAME preadministration had no effect on the spinal Fos expression evoked by sham operation.


CONCLUSIONS
Spinal Fos expression could be induced by different mechanisms, and it should not regarded as a reliable marker of pain sensation disorders. NO plays an important role in the development of nociception and spinal Fos expression through central sensitization mediated by peripheral nerve injury.
Li
Ping
P
Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Xue
Fu-Shan
FS
Li
Cheng-Wen
CW
Liu
Kun-Peng
KP
Liu
Yi
Y
Xu
Ya-Chao
YC
Yang
Quan-Yong
QY
D000818:Animals; D004285:Dogs; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry; D007278:Injections, Spinal; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000502:physiology; D020671:Posterior Horn Cells / Q000737:chemistry*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000503:physiopathology
D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester