Effect of compound K on spinal Toll-like receptor 4 expression during morphine-induced hyperalgesia in rats

Abstract

Objective To evaluate the effect of compound K (CK) on spinal Toll-like receptor 4 (TLR4) expression during morphine-induced hyperalgesia in rats. Methods Thirty-six healthy male Sprague-Dawley rats in which intrathecal catheters were successfully implanted were randomly divided into 3 groups (n=12 each) using a random number table: control group (group C), morphine-induced hyperalgesia group (group M), and morphine + CK group (group M+ CK). Starting from 5 days after successful implantation, normal saline 10 μl, morphine 10 μg, and morphine 10 μg + CK 10 μg were injected intrathecally twice a day for 7 consecutive days.Tail-flick latency (TFL) to a thermal nociceptive stimulus was measured at 1 day before administration (T0, baseline) and at 30 min after the initial administration on 1st, 3rd, 5th and 7th days (T1-4), and the percentage of maximum possible effect (MPE) was calculated.The rats were sacrificed after the last measurement of tail-flick latency, and the lumbar segment (L3-5) of the spinal cord was removed for determination of the expression of TLR4 by Western blot. Results MPE was significantly lower at T3, 4 than at T1 in M and M+ CK groups (P<0.05). Compared with group C, MPE was significantly lower at T2-4, and the expression of TLR4 was up-regulated in M and M+ CK groups (P<0.05). Compared with group M, MPE was significantly increased at T1-4, and the expression of TLR4 was down-regulated in group M+ CK (P<0.05). Conclusion The mechanism by which CK alleviates morphine-induced hyperalgesia is associated with down-regulation of TLR4 expression in rats. Key words: GINSENOSIDE; Morphine; Hyperalgesia; Toll-like receptor 4; Spinal cord