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. 2021 Mar 26;15:593654. doi: 10.3389/fnins.2021.593654

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Copyright © 2021 Huang, Jiao, Zhu, Xiong, Lu, Ai, Yang, Zhao and Xu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The expression of spinal NO in the rats subjected or not subjected to chronic RS and effect of L-NAME on the nociceptive behavior and spinal NO in the rat models of RS. (A) The expression of spinal NO in the rats subjected or not subjected to chronic RS, P < 0.001. (B) Effects of either DAHP or BH4 intrathecal administration on spinal NO in rats subjected to chronic RS. Chronic RS rats received chronic intrathecal treatment with either DAHP (6 mg/kg) or BH4 (1 μg/ml, 10 μl) from the first day of establishing chronic RS until the end of the experiment, F_2,15 = 67.94, P < 0.001. (C–E) Effect of L-NAME intrathecal administration on nociceptive behavior in rats subjected to chronic RS; chronic RS rats that received chronic intrathecal treatment with L-NAME (30 μg/μl, 10 μl) 30 min prior to BH4 (1 μg/ml, 10 μl), L-NAME (30 μg/μl, 10 μl), and BH4 (1 μg/ml, 10 μl) treatment. Nociceptive behavior tests including PWMT (treatment: F_3,33 = 47.94, P < 0.001; observation intervals: F_3,99 = 49.132, P < 0.001; interaction: F_9,99 = 16.453, P < 0.0001), PWTL (treatment: F_3,33 = 34.594, P < 0.001, observation intervals: F_2,66 = 1.131, P = 0.329; interaction: F_6,66 = 3.15, P = 0.009), and TFL (treatment: F_3,33 = 22.943, P < 0.001; observation intervals: F_2,66 = 1.598, P = 0.21; interaction: F_6,66 = 2.904, P = 0.014). (F) Effect of intrathecal administration of L-NAME on the expression of spinal NO, F_3,20 = 51.906, P < 0.001. *Significant difference with respect to control or vehicle groups (two-way ANOVA with repeated measures). *P < 0.05 and ***P < 0.001. NO, nitric oxide; RS, restraint stress; L-NAME, N^ω-nitro-L-arginine methyl ester; NO, nitric oxide; BH4, tetrahydrobiopterin; PWMT, paw withdrawal mechanical threshold; PWTL, paw withdrawal thermal latency; TFL, tail-flick latency.