Effects Of Intrathecal PSD-93 Antisense Oligonucleotide On Neuropathic Pain Of Rats After C7 Spinal Nerve Compression

Objective To investigate the role of spinal PSD-93 and Neuronal nitric oxide synthase (nNOS) in the development of rats' neuropathic pain induced by C7 spinal nerve compression (C7SNC), observe the effects produced by intrathecal(IT) PSD-93 antisense oligonucleotides(AS ODN), and explore a novel way to manage neuropathic pain.Methods Sixty male SD rats were randomly divided into 5 groups (n=12 each): group C sham surgery + NS 10ul; group N C7SNC + NS 10ul; group M C7SNC + Missense oligonucleotide ( MS ODN) 10μg; group A1 C7SNC + AS ODN 5μg; group A2 C7SNC + AS ODN 10μg. C7SNC was produced by placing a microvascular clamp, which has a magnitude of 60 grams, on the right C7spinal nerve of rat for 15 minutes. All of rats were performed cervical IT intubation immediately after C7SNC. After finishing the surgery, normal saline or AS ODN or MS ODN was injected IT once a day for 4 consecutive days. Threshold to noxious thermal and mechanical stimuli was measured before surgery (baseline) and on the 1st, 3rd, 5th and 7th day after surgery. On the 3rd or 7th day after surgery, six rats of each group were killed and the C7 spinal cord was removed for determination of the PSD -93 protein and nNOS expression by the method of immunohistochemistry. Results1. During the 1st to the 7th day after surgery, the threshold to mechanical and thermal stimuli on the surgery side was significantly higher in group N and M than in group C. On the 1st and 3rd day or during the 1st to the 7th day after surgery respectively, the threshold to mechanical and thermal stimuli on the surgery side were significantly higher in group A1 or A2 than in group N and M.2. On the 3rd and 7th day after surgery, the expression of spinal PSD-93 or nNOS was higher in group N and M than in group C, but lower in group A2 than in group N and M. On the 3rd day, the expression of spinal PSD-93 or nNOS was lower in group A1 than in group N and M. On the 3rd and 7th day, the expression of spinal PSD-93 or nNOS was lower in group A2 than in group A1.3. PSD-93 and nNOS positive cells were similar in the distribution and shape on the dorsal hall of spinal cord.. On the 3rd and 7th day aider surgery, respectively, the immunohistochemical scales of PSD-93 and nNOS were correlated with each other. On the 3rdday, r=0.937, p＜0.001; on the 7th day, r=0.819, p＜0.001。Conclusion1. Increased expression of spinal PSD-93 and nNOS may contribute to the development of neuropathic pain induced by C7SNC. 2. Spinal PSD-93 may modulate nNOS during the development of neuropathic pain.3. IT PSD-93 AS ODN can reduced the neuropathic pain probably through inhibition of spinal PSD-93 and nNOS, and the effects of PSD-93 ASOND were dose dependent, i.e. 10μg is better than 5μg.