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BACKGROUND: The pathogenesis of chronic pathological pain is yet unknown. Some studies have shown that after spinal cord injury, CCL21 can activate microglia in the central nervous system and is expressed only in damaged neurons, promoting the formation of chronic pathological pain. OBJECTIVE: To investigate whether the anterior cingulate cortex is involved in the formation of chronic pathological pain after inferior orbital nerve ligation in rats, and whether blocking chemokine CCL21 in the anterior cingulate cortex can reduce the chronic neuropathic pain. METHODS: A total of 80 male Sprague-Dawley rats were randomly divided into 4 groups with 20 rats in each group. In the sham group, only the infraorbital nerve of the rats was exposed; in the model group, the left infraorbital nerve was ligated; in the anti-CCL21 group, CCL21 neutralizing antibodies was administered to the anterior cingulate cortex of the rats on the 7th day after surgery; and in the PBS control group, PBS solution was given into the anterior cingulate cortex of rats on the 7th day after surgery. Rats in the sham and model groups were subjected to behavioral tests on the 3rd, 5th, 7th, and 14th days after surgery, and those in the anti-CCL21 and PBS control groups were subjected to the behavioral test at 6 hours after administration. All rats were sacrificed under anesthesia after behavioral tests. The cortical tissues were taken from the anterior cingulate, and the protein content of CCL21 was determined by western blot and immunofluorescence. RESULTS AND CONCLUSION: The pain threshold of the rats in the model group was lower than that in the sham group, and the expression of CCL21 in the anterior cingulate cortex was significantly higher in the model group than the sham group. After the administration of CCL21 neutralizing antibody, the expression of CCL21 was reduced to some extents, and the rat pain threshold was increased accordingly. These findings reveal that the anterior cingulate cortex of rats may be involved in the production of chronic pathological pain, and the administration of CCL21 neutralizing antibody can relief the pain.
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Aim To investigate the antagonistic effect of resveratrol on neuropathic pain and its underlying mechanism. Methods Neuropathic pain was induced by ligation of L5 spinal nerve (SNL) in rats. 90 male Sprague-Dawley rats, fit with intrathecal catheters were divided randomly into six groups ( n = 15 ): naive group; sham group; SNL group; high dosage of res-veratrol group (300μg);middle dosage of resveratrol group ( 30μg ) and low dosage of resveratrol group (3μg). The naive group did not make any process. In sham group, the L5 spinal nerve was only exposed without ligation. Other groups received SNL. Different dosages of resveratrol dissolved in 10μL 100% DMSO were administered by intrathecal injections once a day for 4 days, starting on day 4 after SNL. Paw withdraw-al latency (PWL) was measured on day 1,3,5,7,9, 11,14 days after surgery separately. On day 7 after be-havioral testing, the lumbar segments of the spinal cord were removed to measure the level of SIRT1 and acety-lated-p65(Ac-p65) for western blot. The activation of NF-κB was determined through calculating the percent-age of NF-κB-immunofluorescence positive staining cells in this study. Results Compared with sham groups,the SNL group showed an obvious decrease(P< 0. 05) of PWL and SIRT1 after surgery,whereas Ac-p65 and actived NF-κB significantly increased ( P <0. 05) in the spinal cord. Administration with high and middle dosages of resveratrol markedly attenuated(P <0. 05) SNL-induced thermal hyperalgesia and down-regulation of SIRT1 and blocked (P < 0. 05) the SNL-induced up-regulation of Ac-p65 and actived NF-κB in the spinal cord. Conclusion Intrathecal resveratrol can inhibit the development of neuropathic pain and suppress the activation of NF-κB signaling in SNL rats . The analgesic effect of resveratrol is implemented partly via increasing the level of SIRT1 and deacetylat-ing p65.
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Objective To explore the effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinolon on hyperalgesia in a rat model of L5 spinal nerve ligation and its underlying mechanism. Methods After lumber intrathecal catheters implanted,90 male Sprague-Dawley rats (40-50 d,weighing 180-220 g)were randomly divided into six groups (n=15 each):Naive group (group N),Sham operation group (group S),SNL group (group C)and three Garcinol treatment groups (group H:500μg/kg,group M:100μg/kg,group L:20μg/kg).Group N did not receive any operation in rats.In group S,the L5 spinal nerve was only exposed without ligation.Other four groups all received spinal nerve ligation (SNL).Group N,group S and group SNL were administrated intrathcelly with 100% DMSO (10 μl)within 3 to 6 days after SNL surgery.Other three groups were treated with Garcinol 500μg/kg (group H),100μg/kg (group M),20 μg/kg (group L)at the same points respectively.Behaviorally,thermal withdrawal latency (TWL) were measured at 1 day (T0 )before and on days 1(T1 ),3(T2 ),5(T3 ),7(T4 ),9(T5 ),11(T6 ),14(T7 )after surgery separately.On the 7th day after behavioral testing,the lumber segment of the spinal cord was removed to test the level of p300 and acetyl-p65 by western blot,while NF-κB was detected with immunofluorescence. Results Compared with group N,TWL was significantly shortened in group C,L,M and H,the levels of ace-tyl-p65 and p300 in group C,L,M and H were markedly increased,the expression of NF-κB in group C,L,M and H was markedly increased(P<0.05).Compared with group C,TWL was significantly prolonged in group M and group H,the levels of acetyl-p65 and p300 in group M and group H were dramatically decreased,the expression of NF-κB in group H was obviously decreased(P <0.05).Conclusion The acetyltransferase p300 inhibitor Garcinol imposes protective effect in SNL-induced neuropathic pain.Mechanisms are probably associ-ated with decreasing acetyl-p65 protein expression level in the NF-κB pathway.
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Objective Controversies remain as to the recovery time, recovery quality, and incidence of peri-recovery adverse reactions of the patient receiving general anesthesia with remifentanil and sufentanil.This study aimed to systematically assess the qual-ity of recovery from general anesthesia with remifentanil and sufentanil. Methods Randomized controlled trials ( RCTs) were re-trieved from The Cochrane Library, PubMed, MEDLINE, EMbase, Ovid, Springer, Web of Science, CNKI, CBM, VIP, and Wan-Fang Data.According to the modified Jadad quality scale, the literature retrieved was screened and subjected to quality evaluation and meta-analysis was performed on the included studies using the RevMan 5.1 software. Results Thirty-three RCTs involving 2175 pa-tients were finally included.The results of meta-analysis showed no significant differences between the remifentanil and sufentanil groups undergoing thyroid surgery either in the recovery time to spontaneous breathing ( T1) and eye-opening ( T2) and endortracheal extubation time ( T3 ) ( P >0.05 ) or in the incidence rate of postoperative nausea and vomiting (PONV) (P>0.05).T1, T2 and T3 were significantly shorter in the sufentanil than in the remifentanil group in other types of surgery (P<0.05).The patients with level-1 Ramsay score were remarkably more in the remifentanil than in the sufentanil group ( MD =13.67, 95% CI 2.67 -69.91 ) ( P <0.05), and the VAS scores were markedly higher in the former than in the latter group at 30 minutes (MD=3.37, 95% CI 3.28-3.46) and 1 hour after extubation (MD=2.53, 95% CI 2.43 -2.63) (P<0.05). Conclusion Compared with sufentanil, remifentanil provides a quicker recovery but a weaker analgesia effect and a higher rate of post-operative agitation.However, sufentanil produces a better pain relief and a higher quality of recovery after operation.