Spinal immunohistochemical NOS positive neurons and hyperalgesia model in rats.

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Nitric oxide is regarded as a potent, atypical neuromodulator that is produced from L-arginine by nitric oxide synthase. Neuronal nitric oxide synthase is localized not only in the brain but also in the spinal cord. Recent data indicate that nitric oxide in the spinal cord may play a role in the pathphysiology of pain following nerve injury. We therefore determined the relationship between pain bethavior and alterations in the number of neuronal nitric oxide synthase-positive neurons in the spinal cord in rat models of nerve injury. A model of neuropathic pain (left L5, L6 spinal nerve ligations) was compared to models of spinal nerve (L5, L6) avulsion or crush injuries. Sham controls inculuded rats where the spinal nerves were exposed but not manipulated. After institutional approval 76 male Sprague-Dawley rats were included in this study. They were divided into 5 groups ; Ligation (n=18), Avulsion (n=17), Crush (n=17), Sham Control (n=18), and Normal Control (n=6) groups. Paw withdra … More wal thresholds and frequency of responses to mechanical stimuli were determined and nNOS immunohistochemical staining of the spinal cord sections at the T1, L1, L5 and L6 levels were performed at 4 days, 1 week, and 3weeks after surgery. The number of neuronal nitric oxide synthase-positive neurons at dorsal horus, central canal, and intermediolateral cell columns were correlated with the paw withdrawal responses to mechanical stimulation of left hind paw. The Ligation group rats showed overt mechanical hyperalgesia while the Avulsion and Crush groups of rats were anesthetic in the sciatic distribution. The quantitative histochemical analysis of neuronal nitric oxide synthase-positive neurons revealsd that the Ligation group developed increased number of neuronal nitric oxide synthase-positive neurons in the left (ipsilateral) dorsal horn 4 days through 3 weeks after surgery at the L1, L5 and L6 levels and those in left intermediolateral cell column 1 and 3 weeks after surgery at the L1 level. In contrast, Avulsion and Crush groups demonstrated a decreased number of neuronal nitric oxide synthase-positive neurons in the left dorsal horn 1 and 3 weeks after surgery at the L1, L5 and L6 levels. There were significant correlations between the decrease in paw withdraw threshold ; i.e., mechanical hyperalgesia, and the number of neuronal nitric oxide synthase-positive neurons in the left dorsal horn at L1, L5 and L6 levels in the Ligation group. The results of this study indicate that nitric oxide may be involved in the mechanism of neuropathic pain that results from partial nerve injuries. Less