Role of HDAC6 in spinal dorsal horn in dexmedetomidine-induced reduction of neuropathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in spinal dorsal horn in dexmedetomidine-induced reduction of neuropathic pain (NP) in rats.Methods:Forty clean-grade healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 190-240 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), sham operation group (group SH), group NP, dexmedetomidine group (group D), and specific HDAC6 inhibitor ACY-1215 plus dexmedetomidine group (group AD). The animals were commonly fed without any treatment in group C. The sciatic nerve was only isolated but not ligated in group SH.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI). The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1-mm intervals with 4-0 silk thread in NP and D groups.In group D, dexmedetomidine 40 μg/kg was intraperitoneally injected once a day starting from the end of operation until the animals were sacrificed.In group AD, ACY-1215 25 mg/kg was intraperitoneally injected every day immediately before CCI, and dexmedetomidine 40 μg/kg was intraperitoneally injected daily after CCI until 15 days after CCI.The equal volume of solvent was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (baseline, T 0) and 3, 6, 9, 12 and 15 days after CCI (T 1-5). The rats were then sacrificed, and the dorsal horn tissues of L 4-6 spinal cord were obtained for determination of the expression of myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) p65 by Western blot. Results:Compared with group C and group SH, the MWT was significantly decreased, and the TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was up-regulated in NP, D and AD groups ( P<0.05). Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T 1-5, the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was down-regulated in group D ( P<0.05), and no significant change was found in the parameters mentioned above in group AD ( P>0.05). Compared with group D, MWT was significantly decreased, and TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 was up-regulated in the dorsal horn of the spinal cord in group AD ( P<0.05). Conclusion:HDAC6 in spinal dorsal horn is involved in dexmedetomidine-induced reduction of NP in rats, which is related to inhibiting MyD88/NF-κB signaling pathway.