Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats.

Purpose: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca2+)-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α2) adrenoreceptor agonist that mediates intracellular Ca2+ levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG). Methods: The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Results: Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors. Conclusion: The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG.

Effect of dexmedetomidine anesthesia on perioperative levels of TNF-α and IL-6 in patients with ovarian cancer.

Effect of continuous use of dexmedetomidine during general anesthesia on perioperative levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients undergoing radical resection of ovarian cancer was investigated. The initial treatment of ovarian cancer is mainly radical surgery. Most patients with ovarian cancer radical surgery can achieve good results, but the use of improper anesthetic drugs in radical surgery can easily lead to unstable patient vital signs. Therefore, the selection of appropriate anesthetic drugs has become the key to radical ovarian cancer surgery. There are few reports on the use of dexmedetomidine in anesthesia for ovarian cancer radical surgery. This study was performed to retrospectively analyze the case data of patients undergoing laparoscopic ovarian cancer radical surgery, and to compare the hemodynamics of dexmedetomidine anesthesia with midazolam anesthesia and the concentrations of TNF-α and IL-6, to provide reference for clinical implementation of ovarian cancer radical surgery. The hemodynamics of patients in the dexmedetomidine group were stable compared with the midazolam group. Serum TNF-α and IL-6 levels were significantly lower in the dexmedetomidine group than that in the midazolam group. If dexmedetomidine were continuously used during general anesthesia, the perioperative serum levels of TNF-α and IL-6 could be effectively reduced in patients undergoing radical resection of ovarian cancer, and the perioperative stress response was suppressed.

Effects of flurbiprofen on serum level of interleukin-6, prostacyclin and corticosteroid A2 in patients with bone metastases of cancer.

The present study aimed to investigate the effects of flurbiprofen on serum level of interleukin-6 (IL-6), prostacyclin (PGI2) and corticosteroid A2 (TXA2) in patients with bone metastases of cancer. A total of 210 patients with bone metastasis of cancer were randomly divided into two groups: Flurbiprofen axetil analgesia group (group A) and dezocine analgesia group (group B), 105 cases in each group. The analgesic effect was evaluated using visual analogue scale (VAS) scoring system at 1, 12, 24 and 48 h after treatment. Serum levels of IL-6, PGI2 and TXA2 at 12 and 24 h after treatment were detected using double-antibody sandwich enzyme-linked immunosorbent assay. No significant differences in VAS scores were found between the two groups at 1, 12, 24 and 48 h after treatment, and no gastrointestinal adverse events and abnormal bleeding were observed. No significant differences in the serum levels of IL-6 were found between the two groups at 12 and 24 h after treatment. Significantly lower serum levels of TXA2 and PGI2 were found in group A compared to group B at 12 and 24 h after treatment (P<0.05). Serum level of PGI2 was positively correlated with serum level of TXA2 (r=0.7212, P<0.05) and VAS score (r=0.7159, P<0.05). Serum level of IL-6 was positively correlated with VAS score (r=0.7997, P<0.05). The results show that flurbiprofen axetil can effectively relieve pain in patients with bone metastases of cancer, can inhibit platelet activation, adhesion and aggregation, and reduce the formation of deep vein thrombosis, and can inhibit stress response and inflammatory response in the body.

Structure-based rational design of self-inhibitory peptides to disrupt the intermolecular interaction between the troponin subunits C and I in neuropathic pain.

The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC-TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders. Molecular dynamics simulation and binding free energy analysis suggests that the switch peptide can interact with TnC in a structurally and energetically independent manner. Terminal truncation of the peptide results in a number of potent TnC binders with considerably simplified structure and moderately decreased activity relative to the native switch. We also employ fluorescence polarization assays to substantiate the computational findings; it is found that the rationally designed peptides exhibit moderate or high affinity to TnC with dissociation constants KD at micromolar level.

Correlations of O3 therapeutic targets and imaging localization in lumbar intervertebral disc protrusion.

OBJECTIVE: This study aims to investigate correlations between the effects of O3 target-injection treatment and imaging localization in lumbar intervertebral disc protrusion (LIDP). METHODS: 164 LIDP patients were divided into 3 groups: group A, the protrusion located at level I-III, region 1-2, domain a-b; group B, the protrusion located at level I-III, region 1-2, domain c-d; group C: the protrusion located at level I-III, region 3-4, domain a-b. The patients were treated with LIDP O3-target treatment + blocking therapy with epidural anti-inflammatory analgesic liquid. RESULTS: Among the 164 LIDP patients, 95 patients (57.93%) exhibited the significant effectiveness after the treatment; 64 cases (39.02%) exhibited the effectiveness. The results of functional improvements revealed that 50 cases (53.76%) of sagittal plane and 54 cases of horizontal plane (55.67%) in the group A, 33 cases (35.48%) and 31 cases (31.96%) in the group C respectively were significantly better than those in the group B (10 cases, 10.75%; 12 cases, 12.37%) (P < 0.05). The visual analogue scale (VAS) scores 1 week and 1 month after the treatment in the three groups were significantly decreased than those before the treatment (P < 0.05). The intergroup comparison revealed that the A group (1 week 2.28 ± 0.85, 1 month 1.21 ± 0.27) and C (2.79 ± 0.98, 1.38 ± 0.55) were significantly better than the B group (3.92 ± 1.14, 2.53 ± 0.51) (P < 0.05). CONCLUSIONS: The O3 target-injection treatment exhibited the best effects in treating the LIDP patients with the protrusion located at level I-III, region 1-2, domain a-b.

CGRP 4218T/C polymorphism correlated with postoperative analgesic effect of fentanyl.

PURPOSE: Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. METHODS: 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. RESULTS: The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (P<0.05). Meanwhile, the fentanyl consumption of the C/C group was much higher than the T/T group (P<0.05) at the 12th hour and the 24th hour. Besides, the fentanyl consumption of the C/C group was more than the T/C group (P<0.05) at the 24th hour. The differences in NRS scores, Ramsey scores, and postoperative adverse reactions between each group at all time points were not statistically significant. CONCLUSIONS: CGRP 4218T/C polymorphism may be associated with the postoperative fentanyl consumption for analgesia.