Role of HDAC6 in maintanence of neuropathic pain in rats: relationship with MyD88/NF-κB signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in the maintanence of neuropathic pain (NP) and the relationship with myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway in the rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-260 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), sham operation group (group S), NP group and NP plus HDAC6 inhibitor ACY-1215 group (group NP+ ACY). The rat model of NP was established by ligating the L 5 spinal nerve in anesthetized rats.The L 5 spinal nerve was only exposed without ligation in group S. In NP+ ACY group, ACY-1215 25 mg/kg was intraperitoneally injected daily for 21 days after the end of model establishing.The equal volume of solvent was intraperitoneally injected in S and NP groups, and group C was reared normally.The mechanical paw withdrawal threshold (MWT) was measured on 3 days before establishing the model (T 0), the day before establishing the model (T 1) and 1, 3, 7, 10, 14 and 21 days after establishing the model (T 2-7). The rats were sacrificed after measurement of MWT on day 21 after ligation, and the spinal dorsal horn tissues of L 4-6 were removed for determination of the expression of MyD88, NF-κB and phosphorylated NF-κB (p-NF-κB) (by Western blot) and expression of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) mRNA (by real-time polymerase chain reaction). Results:Compared with C and S groups, the MWT was significantly decreased at T 2-7, and the expression of MyD88, NF-κB, p-NF-κB, TNF-α mRNA and IL-1β mRNA was up-regulated in NP and NP+ ACY groups ( P<0.05). Compared with group NP, the MWT was significantly increased at T 5-7, and the expression of MyD88, NF-κB, p-NF-κB, TNF-α mRNA and IL-1β mRNA was down-regulated in group SNL+ ACY ( P<0.05). Conclusion:HDAC6 activation is involved in the maintanence of NP, which is related to activating MyD88/NF-κB signaling pathway in the rats.