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Background Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K+ channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Methods Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. Results We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Conclusion Taken together, these findings indicate that KCNQ channel plays a significant role in controlling cold sensitivity and is a therapeutic target for alleviating trigeminal neuropathic pain that manifests orofacial cold hyperalgesia.

Remimazolam's benefits for patients undergoing painless flexible fiberoptic bronchoscopy remain uncertain. We aimed to compare the efficacy and safety of remimazolam and dexmedetomidine in flexible fiberoptic bronchoscopy (FFB). Randomized controlled trial. University hospital. Between April 2021 and September 2022, patients undergoing painless flexible fiberoptic bronchoscopy were recruited. The patients were randomly assigned with a 1:1 ratio to remimazolam-remifentanil group (RR group) or dexmedetomidine-remifentanil group (DR group). The primary outcome was the procedure interruption rate during bronchoscopy. Secondary outcomes were hemodynamic changes, resuscitation time, rescue medication usage rate and dose, satisfaction scores of patients and bronchoscopists, operation-related complications, and adverse events. A total of 363 patients were included for final analysis. The interruption rates of bronchoscopy were 8.2 % in the RR group and 39.2 % in the DR group (P < 0.05). The rescue medication usage rate (4.4 % vs. 38.7 %, P < 0.05) and dose (1.51 ± 8.15 mg vs. 13.17 ± 18.86 mg, P < 0.05) were lower in the RR group compared with the DR group. The incidence of oxygen desaturation was significantly lower in the RR group than in the DR group (14.3 % vs. 44.2 %, P < 0.05). Hemodynamic changes in patients in the DR group were significant, with longer recovery time and lower satisfaction scores for both inpatients and bronchoscopists (P < 0.05), compared with the RR group. However, there were no significant differences between groups in terms of operation-related complications (P > 0.05) except for postoperative dizziness, which was more common in the DR group (P < 0.05). Remimazolam is effective and safe in painless flexible fiberoptic bronchoscopy. It allows a lower procedure interruption rate and incidence of oxygen desaturation, providing better hemodynamic stability compared to dexmedetomidine. •Remimazolam, an ultra-short-acting benzodiazepine, induced better sedation during bronchoscopy than dexmedetomidine.•Remimazolam had a better safety profile than that of dexmedetomidine.•Remimazolam anesthesia had higher bronchoscopist and patient satisfaction score.

Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

Purpose: To explore the efficacy of nimodipine, nifedipine, and edaravone (EDA) combined with Nao-Xue-Shu in patients with hypertensive intracerebral hemorrhage (HICH) and to determine the best western medicine combined with Nao-Xue-Shu for treating HICH patients using a ranking method. Methods: After a comprehensive search of the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP information database, Chinese Biomedical Database (CBM), PubMed, Embase, and Cochrane Library database from the database establishment 31 December 2021, data extraction and quality assessment were conducted for the included articles. The primary outcome measure was the effectiveness after treatment. Secondary outcome measures were after-treatment the National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume, perihematoma edema volume, and inflammatory factor expression levels. Statistical analyses were performed using Stata 16.0 and RevMan 5.3.0 software. Results: We included 19 randomized controlled trials (RCTs) and six non-RCTs. The effective rate after treatment was ranked from the best to the worst as follows: routine cure measure (RCM) + nifedipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA, and RCM. The post-treatment NHISS scores from lowest to highest were as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + EDA, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment hematoma volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment perihematoma edema volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM. For inflammatory factor expression levels after treatment, IL-6 concentration levels after treatment from lowest to highest wasas follows: RCM + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, and RCM. TNF-α concentration levels after treatment from lowest to highest was as follow: RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM. Conclusion: Nao-Xue-Shu combined with nifedipine showed better effectiveness after treatment in HICH patients compared with the other combinations. Nao-Xue-Shu combined with EDA was more effective for improving neurological function and reducing both hematoma and edema volumes around the hematoma compared with the other combinations. However, Nao-Xue-Shu alone or Nao-Xue-Shu combined with nimodipine may be more effective for reducing proinflammatory factor expression.

Study designSystematic review with network meta-analysis.ObjectiveWe explored the efficacy and safety of different drug treatments in patients with spinal-cord injury (SCI)-related neuropathic pain. We investigated which treatment is most suitable for such patients by judging the efficacy and safety of these drugs.MethodsWe searched the PubMed, Medline, Embase and Cochrane databases from inception to 31 August 2020. The quality of the included studies was assessed. We selected the proportion of patients whose pain was reduced by ≥50% and the prevalence of adverse effects as the outcome indicators of efficacy and safety, respectively.ResultsWe included 15 randomized controlled clinical trials involving five interventions (anticonvulsants, antidepressants, anesthetics, opioids and botulinum toxin A). Based on the proportion of patients with pain reduction ≥50%, the order (from highest to lowest) was anticonvulsants > anesthetics > antidepressants > botulinum toxin A > opioids > placebo. With regard to the prevalence of adverse effects, the order of safety (from highest to lowest) was placebo > antidepressants > botulinum toxin A > anticonvulsants > opioids > anesthetics. Analyzes of efficacy and safety revealed that anticonvulsant, antidepressant and botulinum toxin A have good efficacy and safety.ConclusionThe efficacy of anticonvulsants, anesthetics, antidepressants, opioids and botulinum toxin A was greater than that of placebo for treatment of SCI-related neuropathic pain. However, the prevalence of adverse effects associated with use of these drugs was also higher than that of placebo. Further analyses based on efficacy and safety revealed anticonvulsants to be more suitable for such patients. In addition, antidepressant and botulinum toxin A may be promising treatments for SCI-related neuropathic pain, however, their effects still need to be further explored due to the small sample size.