Pharmacology/Drug Development

Sufentanil, a potent opioid, serves as the first option for perioperative analgesia owing to its analgesic effect, long duration and stable hemodynamics, whereas its side effects frequently blunt its application. The intravenous (IV) injection of sufentanil during anesthesia induction has high incidence of choking or bucking reaction, which is defined as sufentanil-induced cough (SIC). Moreover, postoperative nausea and vomiting (PONV) is a common and stressful complication, which is also related to the usage of opioid. High incidence of PONV is reported in the patients with SIC. Hence, we sought to determine whether naloxone, an opioid antagonist, at low dose would decrease the incidences of SIC and PONV. 216 female patients undergoing gynecological laparoscopic operation (<2 h) under general anesthesia were recruited in this study, and randomly assigned into two groups: Group N (patients receiving naloxone and Group C (patients receiving vehicle). Sufentanil (0.5 μg/kg within 5 s) was given in anesthesia induction, and low-dose naloxone (1.25 μg/kg) or identical vehicle was initially injected 5 min prior to induction, with the incidence and severity of SIC estimated. Subsequently, naloxone or vehicle was continuously infused at the rate of 0.5 μg/kg/h in the initiation of operation until the end of the operation, and the transverse abdominal fascia block (TAP) was performed for postoperative analgesia. The PONV profiles such as incidence and the severity, grading, and the frequencies of antiemetic usage within 24 h were evaluated, with VAS scores and remedial measures for analgesia during the first 24 h postoperatively were recorded. Our results revealed that one bolus of low-dose naloxone prior to the induction significantly mitigated the incidence of SIC, and intraoperative continuous infusion of low-dose naloxone reduced the incidence and the severity of PONV, so that the postoperative VAS scores and further remedial analgesia were not altered. These results not only provide clinical solutions for prophylaxis of SIC and PONV, but also suggests that opioids may act as a key role in both SIC and PONV, whereas opioid antagonist may hit two tasks with one stone. Moreover, further investigations are required to address the underlying mechanism of SIC and PONV. : [www.chictr.org.cn], identifier [ChiCTR2200064865].

The multi-functional neuropeptide calcitonin gene-related peptide (CGRP) plays a major role in the pathophysiology of migraine. The detection of elevated CGRP levels during acute migraine headache was the first evidence of the importance of the peptide. Since then, elevated CGRP levels have been detected not only during spontaneous and experimentally induced migraine attacks but also interictally. However, the detection of CGRP in peripheral blood shows conflicting results. In this respect, alternative detection methods are needed and have been already proposed. This article summarizes what we have learned from studies investigating CGRP in jugular and peripheral blood and reviews the latest state of research concerning the detection of CGRP in saliva and tear fluid as well as their contribution to our understanding of migraine pathophysiology.

Intervertebral disc degeneration is a progressive and chronic disease, usually manifesting as low back pain. This study aimed to screen effective biomarkers for medical practice as well as figuring out immune infiltration situations between circulation and intervertebral discs. Gene expression profiles of GSE124272 was included for differentially analysis, WGCNA and immune infiltration analysis from GEO database, and other GSE series were used as validation datasets. A series of validation methods were conducted to verify the robustness of hub genes, such as principal component analysis, machine learning models, and expression verification. Lastly, nomogram was established for medical practice. 10 genes were commonly screened combination of DEGs, WGCNA analysis and lipid metabolism related genes. Furthermore, 3 hub gens CYP27A1, FAR2, CYP1B1 were chosen for subsequent analysis based on validation of different methods. GSEA analysis discovered that neutrophil extracellular traps formation and NOD-like receptor signaling pathway was activated during IDD. Immune infiltration analysis demonstrated that the imbalance of neutrophils and γδT cells were significantly correlated with IDD progression. Nomogram was established based on CYP27A1, FAR2, CYP1B1 and age, the calibration plot confirmed the stability of our model. CYP27A1, FAR2, CYP1B1 were considered as hub lipid metabolism related genes (LMRGs) in the development of IDD, which were regarded as candidate diagnostic biomarkers especially in circulation. The effects are worth expected in the early diagnosis of IDD through detecting these genes in blood.

Cervical epidural steroid injections have long been utilized to treat intraspinal inflammation causing cervicalgia and/or cervical radiculopathy, and much has been written about safety and efficacy. There are published opinions, without evidence basis, that these injections should not be performed above C7-T1 for fear of dural puncture, spinal cord injury, and other complications that might occur more frequently at higher spinal levels. However, many experienced interventional pain physicians believe that epidural injections targeted to the level of spinal inflammation may be more effective. Although medication injected at the lowest cervical level C7-T1 may ascend to higher spinal levels, it often does not since inflammation and swelling at the cervical level of pathology may increase epidural pressure causing the injectate to move caudally down the path of least resistance.

A high prevalence of patients with spinal cord injury (SCI) suffer from chronic neuropathic pain. Unfortunately, the precise pathophysiological mechanisms underlying this phenomenon have yet to be clearly elucidated and targeted treatments are largely lacking. As an unfortunate consequence, neuropathic pain in the population with SCI is refractory to standard of care treatments and represents a significant contributor to morbidity and suffering. In recent years, advances from SCI-specific animal studies and translational models have furthered our understanding of the neuronal excitability, glial dysregulation, and chronic inflammation processes that facilitate neuropathic pain. These developments have served advantageously to facilitate exploration into the use of neuromodulation as a treatment modality. The use of intrathecal drug delivery (IDD), with novel pharmacotherapies, to treat chronic neuropathic pain has gained particular attention in both pre-clinical and clinical contexts. In this evidence-based narrative review, we provide a comprehensive exploration into the emerging evidence for the pathogenesis of neuropathic pain following SCI, the evidence basis for IDD as a therapeutic strategy, and novel pharmacologics across impactful animal and clinical studies.

No disease-modifying treatments are currently available for osteoarthritis (OA). While many therapeutic approaches are now being investigated it is ethical to resort to alternative solutions as that we already possess. There are many reasons for thinking that, at sufficiently high doses, glucosamine (GlcN) sulphate possesses a clinically relevant effect on OA pain. Wide inter-individual variations in the symptomatic effects of GlcN are explained by the extreme variability of its bioavailability. In studies evaluating its structure-modifying effect, GlcN was more effective than placebo in reducing the rate of joint space narrowing in patients with knee OA. More recent data suggest that GlcN may be effective in the primary prevention of OA in sportsmen. There is no controversy concerning the safety of GlcN which does not differ to that of placebo. Several studies have recently revealed an unexpected effect of GlcN on cardiovascular mortality. After adjusting for confounding factors, the regular consumption of GlcN correlated with a 27% reduction in mortality and a 58% reduction in deaths from cardiovascular causes. These data confirm animal studies demonstrating a protective effect of GlcN against cancer and cardiovascular diseases due to modulation of the O-GlcNAcylation pathway. Disorders in O-GlcNAcylation are involved in diabetes, obesity and cancers, which all feature chronic low-grade inflammation (CLGI). By regulating CLGI, GlcN may be beneficial to the symptoms of OA, its outcome and to that of the concomitant chronic pathologies, making GlcN as a valuable candidate for the treatment of OA in patients with metabolic syndrome, diabetes or cardiovascular diseases.