Relationship between BIP and Na v1.8 in peripheral nerve in a rat model of neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between immunoglobulin heavy chain-binding protein (BIP) and Na v1.8 in peripheral nerve in a rat model of neuropathic pain. Methods:Forty-four SPF healthy male Sprague-Dawley rats, weighing 210-260 g, were used in this study.Neuropathic pain was induced by chronic constriction injury (CCI) in anesthetized rats.The experiment was performed in two parts.Experiment Ⅰ Twenty rats were divided into 2 groups ( n=10 each) using a random number table method: sham operation group (group Sham) and group CCI.Experiment Ⅱ Twenty-four rats were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group Sham), CCI plus normal saline group (group CCI+ NS) and CCI plus BIP inhibitor HA15 group (group CCI+ H). Starting from 4th day after surgery, 0.9% normal saline 1 ml was intraperitoneally injected in group CCI+ NS, and HA15 0.7 mg/kg was intraperitoneally injected in group H, once a day for 3 consecutive days.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before surgery and 3, 5 and 7 days after surgery (T 0-T 4), and the expression of BIP and Na v1.8 in dorsal root ganglion (DRG) and sciatic nerve was detected by Western blot on 7th day after completion of behavioral testing in two groups.The expression and colocalization of BIP and Na v1.8 in DRG and sciatic nerve were determined by immunofluorescence on 7th day after completion of behavioral testing in group Ⅰ, and the interaction between BIP and Na v1.8 was evaluated by co-immuno-precipitation. Results:Experiment Ⅰ Compared with group Sham, the MWT was significantly decreased, and TWL was shortened at T 1-T 4, the expression of Na v1.8 in DRG was down-regulated, the expression of BIP was up-regulated, and the expression of Na v1.8 and BIP in sciatic nerve was up-regulated in group CCI ( P<0.05), and BIP and Na v1.8 on the sciatic nerve were co-localized, BIP could co-precipitate Na v1.8 from DRG, and Na v1.8 could also coprecipitate BIP in group CCI.Experiment Ⅱ Compared with group Sham, the MWT was significantly decreased, and TWL was shortened at T 1-T 4, the expression of Na v1.8 in DRG was down-regulated, the expression of BIP was up-regulated, and the expression of Na v1.8 and BIP in sciatic nerve was up-regulated in group CCI+ NS ( P<0.05). Compared with group CCI+ NS, the MWT was significantly increased, and TWL was prolonged at T 3, 4, and the expression of Na v1.8 in DRG was down-regulated in group CCI+ H ( P<0.05). Conclusion:BIP can mediate the redistribution of Na v1.8 in peripheral nerve and is involved in the pathophysiological mechanism of neuropathic pain in rats.