miR-98 acts as an inhibitor in chronic constriction injury-induced neuropathic pain via downregulation of high-mobility group AT-hook 2.

Neuropathic pain, resulting from somatosensory nervous system dysfunction, remains a serious public health problem worldwide. microRNAs are involved in the physiological processes of neuropathic pain. However, the biological roles of miR-98 in neuropathic pain development have not been investigated. Therefore, in our current study, we focused on the effects of miR-98 in neuropathic pain. It was shown that miR-98 was significantly downregulated in chronic sciatic nerve injury (CCI) rat models. In addition, high mobility group A2 (HMGA2) was obviously upregulated in CCI rats. Overexpression of miR-98 inhibited neuropathic pain progression, including mechanical and thermal hyperalgesia. By a bioinformatics analysis, HMGA2 was predicted as a direct target of miR-98. The negative correlation between miR-98 and HMGA2 was validated in our present study. Furthermore, overexpression of miR-98 dramatically repressed HMGA2 protein and messenger RNA (mRNA) expression. Neuroinflammation participates in neural-immune interactions, which can contribute to the neuropathic pain development. Meanwhile, we found that inflammatory cytokine (interleukin [IL]-6, IL-1ß, and COX-2) protein expression in rats infected with LV-miR-98 was greatly suppressed. Taking these results together, we concluded that miR-98 might depress neuropathic pain development through modulating HMGA2.

miR-124-3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2.

Emerging evidence has suggested that microRNAs play a critical role in neuropathic pain development. However, the biological role of miRNAs in regulating neuropathic pain remains barely known. In our present study, we found that miR-124-3p was significantly downregulated in rats after chronic sciatic nerve injury (CCI). In addition, it was showed that overexpression of miR-124-3p obviously repressed mechanical allodynia and heat hyperalgesia. Meanwhile, it has been reported that neuroinflammation can contribute a lot to neuropathic pain progression. Here, we found that inflammatory cytokine (IL-6, IL-1ß, and TNF-⍺) protein expression in rats after CCI greatly increased and miR-124-3p mimics depressed inflammation cytokine levels. Consistently, miR-124-3p alleviated inflammation production in lipopolysaccharide-incubated spinal microglial cells. Bioinformatics analysis revealed that EZH2 acted as a direct target of miR-124-3p, which participated in the miR-124-3p-modulated effects on neuropathic pain development and neuroinflammation. We observed that miR-124-3p was able to promote neuroinflammation and neuropathic pain through targeting EZH2. The direct correlation between them was validated in our current study using dual-luciferase reporter assays. Subsequently, it was manifested that EZH2 abrogated the inhibitory role of miR-124-3p on neuropathic pain progression in CCI rats. Taken these together, our findings highlighted a novel contribution of miR-124-3p to neuropathic pain and indicated the possibilities for developing novel therapeutic options for neuropathic pain.

Effects of miR-26a-5p on neuropathic pain development by targeting MAPK6 in in CCI rat models.

MicroRNA are emerging as significant regulators of neuropathic pain progression. In addition, neuroinflammation contributes a lot to neuropathic pain. miR-26a-5p has been identified as an inflammation-associated miRNA in multiple pathological processes. However, little is known about the biological role of miR-26a-5p in neuroinflammation and neuropathic pain development. Therefore, we aimed to investigate the function of miR-26a-5p in neuropathic pain by establishing a rat model using chronic sciatic nerve injury (CCI). A significant decrease of miR-26a-5p expression was observed in the spinal cord tissues form the CCI rats compared to the control group. Moreover, overexpression of miR-26a-5p significantly repressed neuropathic pain and neuroinflammation in CCI rats. MAPK6 was identified as a direct downstream target gene of miR-26a-5p and confirmed by dual-luciferase reporter assays. As displayed, overexpression of miR-26a-5p greatly reduced MAPK6 levels in vitro and in vivo. Meanwhile, MAPK6 expression and miR-26a-5p were oppositely correlated in CCI rats. Furthermore, up-regulation of MAPK6 obviously reversed the suppressive effect of miR-26a-5p on neuroinflammation and neuropathic pain progression. Taken these together, our results implied that miR-26a-5p could act as a negative regulator of neuropathic pain development through targeting MAPK6, which indicated that miR-26a-5p might serve as a potential therapeutic target for neuropathic pain.

Comparison of the morphine-sparing effect of intraoperative dexmedetomidine with and without loading dose following general anesthesia in multiple-fracture patients: A prospective, randomized, controlled clinical trial.

Intraoperative dexmedetomidine (DEX) with or without loading dose both promote morphine-sparing effect in patient-controlled analgesia on postoperative acute pain. However, the contribution of the loading dose to this effect is largely unknown, especially in long-lasting surgeries. The present study was designed to investigate the role of a loading dose of DEX in this morphine-sparing effect in multiple-fracture patients following general anesthesia.Eighty-six patients scheduled multiple-fracture surgeries under general anesthesia were allocated into 3 groups which were maintained with propofol/remifentanil/Ringer solution (PRR), propofol/remifentanil/DEX with (PRDw), or without (PRDo) DEX loading dose before induction, respectively. Time to first morphine request and 24-hour morphine consumption was monitored. Pain intensity was evaluated with visual analog scale.During the first 24 hours following surgery, patients in the PRDw/o group showed increased time to first request of postoperative morphine and decreased total morphine consumption as compared with PRR patients. There was no significant difference with respect to these parameters between patients from the PRDw and PRDo groups. More patients from the PRDw groups experienced intraoperative bradycardia when compared to those from the PRR or PRDo group.This randomized controlled trial indicates that the morphine-sparing effect of intraoperative DEX was not affected by a loading dose in long-time surgeries.

Sex Differences in the Morphine-Sparing Effects of Intraoperative Dexmedetomidine in Patient-Controlled Analgesia Following General Anesthesia: A Consort-Prospective, Randomized, Controlled Clinical Trial.

Previous studies have reported that intraoperative dexmedetomidine has morphine-sparing effects in patient-controlled analgesia (PCA). The present study was designed to investigate the possible sex differences in the morphine-sparing effects of intraoperative dexmedetomidine following general anesthesia. A total of 223 patients scheduled for surgeries under general anesthesia were divided into female and male groups. Each group was then subdivided into 2 subgroups that were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During the first 24 hours postsurgery, both female and male PRD patients had lower scores on a visual analog scale (VAS) (fPRS vs fPRD, P < 0.05 or P < 0.01; mPRS mPRD, P < 0.05, P < 0.01, or P < 0.001) and consumed less morphine than their controls from the PRS group (fPRS vs fPRD, P = 0.0392; mPRS vs mPRD, P = 0.0041). Interestingly, the female PRD patients had similar VAS scores (fPRD vs mPRD, P > 0.05) and consumed comparable morphine compared to the male PRD patients (fPRD vs mPRD, P = 0.4238). However, when normalized to body weight, they consumed much more morphine than male PRD patients (fPRD vs mPRD, P < 0.001), and this effect was not seen in the PRS patients. Intraoperative administration of dexmedetomidine appeared to have a stronger morphine-sparing effect in controlling postoperative acute pain in male patients than in female patients.

Intraoperative Dexmedetomidine Promotes Postoperative Analgesia and Recovery in Patients after Abdominal Hysterectomy: a Double-Blind, Randomized Clinical Trial.

Surgery-induced acute postoperative pain and stress response can lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia and recovery following abdominal hysterectomy surgeries. Sixty-four patients scheduled for abdominal hysterectomy under general anesthesia were divided into two groups that were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score immediately after extubation than patients in the PRS group. During the first 24 hours post-surgery, PRD patients consumed less morphine with patient-controlled analgesia (PCA) and had lower scores on a visual analogue scale (VAS) than their controls from the PRS group. The global 40-item quality of recovery questionnaire and 9-question fatigue severity score both showed higher recovery scores from day 3 after surgery in the PRD group. with the data are considered together, intraoperative administration of dexmedetomidine appeared to promote the analgesic properties of morphine-based PCA and to expedite recovery following surgery in patients undergoing abdominal hysterectomy.

Intraoperative Dexmedetomidine Promotes Postoperative Analgesia and Recovery in Patients after Abdominal Colectomy: A CONSORT-Prospective, Randomized, Controlled Clinical Trial.

Surgery-induced acute postoperative pain and stress response may lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia and recovery after abdominal colectomy surgeries.Sixty-seven patients scheduled for abdominal colectomy under general anesthesia were divided into two groups, which were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS).During surgery, patients in the PRD group had a lower bispectral index value, which indicated a deeper anesthetic state and a higher sedation score right after extubation, than patients in the PRS group. During the first 24 hours after surgery, PRD patients consumed less morphine in patient-controlled analgesia, and had a lower score in visual analog scale, than their controls from the PRS group. The global 40-item quality of recovery questionnaire and 9-question fatigue severity score both showed a higher recovery score from day 3 after surgery in the PRD group.Intraoperative administration of dexmedetomidine seems to promote the analgesic property of morphine-based patient-controlled analgesia, and speed recovery from surgery in patients after abdominal colectomy.

Intraoperative Dexmedetomidine Promotes Postoperative Analgesia in Patients After Abdominal Colectomy: A Consort-Prospective, Randomized, Controlled Clinical Trial.

Surgery-induced acute postoperative pain may lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia following abdominal colectomy surgeries. Eighty patients scheduled for abdominal colectomy surgery under general anesthesia were divided into 2 groups, which were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score right after extubation than patients in the PRS group. During the first 24 hours post surgery, PRD patients consumed less morphine in patient-controlled analgesia (PCA) and had a lower score in the visual analog scale (VAS) testing than their controls from the PRS group. Intraoperative administration of dexmedetomidine appears to promote the analgesic property of morphine-based PCA in patients after abdominal colectomy.