Relationship between pathomechanism of neuropathic pain-induced depression and autophagy in cortex of frontal lobe in rats

Abstract

Objective To evaluate the relationship between the pathomechanism of neuropathic pain(NP)-inducced depression and autophagy in the cortex of the frontal lobe in rats. Methods Forty healthy male Sprague-Dawley rats in which IT catheters were successfully placed, aged 8-10 weeks, weighing 200-220 g, were divided into 4 groups(n=10 each) using a random number table method: sham operation group(group S), group NP, NP plus dimethyl sulfoxide group(group ND) and NP plus autophagy inducer rapamycin group(group NR). The neuropathic pain model was established by ligation of the left fifth spinal nerve of anesthetized rats in NP, ND and NR groups. Rapamycin 0.1 μg was intrathecally injected via the intrathecal catheter immediately after ligation of the spinal nerve and every day after ligation once a day for 21 consecutive days in group NR. The equal volume of dimethyl sulfoxide was intrathecally injected instead of rapamycin in group ND. The mechanical paw withdrawal threshold(MWT) was measured before ligation and at 1, 3, 7, 10, 14 and 21 days after ligation. The forced swimming test was performed at 3 days before ligation and 14 and 21 days after ligation. The rats were sacrificed after the last measurement of the behaviour testing, and the prefrontal cortex was removed for determination of the expression of microtubule-associated protein light chain 3 Ⅰ(LC3Ⅰ) and LC3Ⅱ, Beclin-1 and p62(by Western blot). The ratio of LC3Ⅱ/LC3Ⅰ was calculated. Results Compared with group S, the MWT was significantly decreased after ligation, the time of immobility was prolonged, the expression of LC3Ⅰ was down-regulated, the expression of LC3Ⅱ, Beclin-1 and p62 was up-regulated, and the LC3Ⅱ/LC3Ⅰ ratio was increased in NP and ND groups(P<0.05). Compared with group NP, the MWT was significantly increased after ligation, the time of immobility was shortened, the expression of LC3Ⅰ and p62 was down-regulated, the expression of LC3Ⅱ and Beclin-1 was up-regulated, and the LC3Ⅱ/LC3Ⅰ ratio was increased in group NR(P<0.05). Conclusion Enhanced autophagy in the cortex of the frontal lobe is involved in the endogenous antidepressant mechanism in rats with NP. Key words: Neuralgia; Autophagy; Frontal lobe; Depression