Pharmacology/Drug Development

Many new first-in-class drugs for neuroscience indications have been introduced in the past decade including new treatments for migraine, amyotrophic lateral sclerosis, depression, and multiple sclerosis. However, significant unmet patient needs remain in areas such as chronic pain, neurodegeneration, psychiatric diseases, and epilepsy. This review summarizes some of the advanced clinical compounds for these indications. Additionally, current opportunities and challenges that remain with respect to genetic validation, biomarkers, and translational models are discussed.

Degeneration of the intervertebral disc is considered to be central in pain pathogenesis in patients suffering from chronic low back pain (LBP). In recent years, the injection of mesenchymal stromal cells (MSCs) into the disc to arrest or reverse the degenerative process has been proposed as an alternative therapy. The aim of the present study was to investigate the feasibility of using iron-labeled MSCs for intradiscal injection in patients with long-standing LBP.

A common expectation for patients after elective spine surgery is that the procedure will result in pain reduction and minimize the need for pain medication. Most studies report changes in pain and function after spine surgery, but few report the extent of opioid use after surgery. This systematic review aims to identify the rates of opioid use after lumbar spine fusion.

At present, the mechanism of siSCN9A in Vincristine (VCR)-induced neuropathic pain (NP) is still unclear. This study aimed to explore the analgesic mechanism of lentivirus-siSCN9A (LV-siSCN9A) infected neurons against NP. 40 male Sprague-Dawley (SD) rats were divided into a control group (injected with normal saline), a model group (VCR-induced NP model), a LV-SC group (NP model mice were injected with LV-SC-infected dorsal root ganglia (DRG) neuron cells under the microscope), and a LV-siSCN9A group (NP model mice were injected with LV-siSCN9A-infected DRG neuron cells under the microscope, with 10 rats in each group. The changes of mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats in different groups were detected by behavior testing, the Nav1.7 changes in each group were detected by immunofluorescence double standard and Western-blot method. It was found that compared with the control group, the MWT and TWL of the rats in model group were significantly decreased ( < 0.05), and the expression levels of Nav1.7 messenger ribonucleic acid (mRNA) and proteins were significantly increased ( < 0.05). Compared with LV-SC group, the MWT and TWL of rats in LV-siSCN9A group were significantly increased ( < 0.05), the expression levels of Nav1.7 mRNA and proteins were significantly decreased ( < 0.05), and the CGRP expression of spinal dorsal horn was significantly decreased. It was concluded that the LV-siSCN9A infected neurons could play an analgesic role by down-regulating Nav1.7 expression induced by VCR in NP model.

We describe here results for the synthesis and synthetic application of 4-amino-3-(arylselanyl)benzenesulfonamides, and preliminary evaluation of antioxidant, anti-edematogenic and antinociceptive properties. This class of compounds was synthesized in good yields by a reaction of commercially available sulfanilamide and diorganyl diselenides in the presence of 10 mol% of I 2 . Furthermore, the synthesized compound 3a was evaluated on complete Freund's adjuvant (CFA)-induced acute inflammatory pain. Dose and time-response curves of antinociceptive effect of compound 3a were performed using this experimental model. Also, compound 3a effect was tested in hot-plate test to evaluate the acute non-inflammatory antinociception. The open field test was performed to evaluate the locomotor and exploratory behaviors of mice. Oxidative stress markers, such as glutathione peroxidase activity; reactive species, non-protein thiols, and lipid peroxidation levels were performed to investigate the antioxidant action of compound 3a . Our findings suggest that the antioxidant effect of compound 3a may contribute to reducing the nociception and suppress the signaling pathways of inflammation on the local injury induced by CFA. Thus, compound 3a reduced the paw edema as well as the hyperalgesic behavior in mice, being a promising therapeutic agent for the treatment of painful conditions.

The current study was designed to test the hypothesis that BmK AGAP (AGAP) potentiates the analgesic effect of lidocaine. The chronic constrictive injury was performed on 72 rats to induce a rapid onset and long-lasting pain. The rats were randomly assigned to one of six groups; Group A (n = 12) received an intrathecal administration of saline, Group B (n = 12) received an intrathecal injection of lidocaine, Group C (n = 12) received an intrathecal administration of AGAP, Group D, E, and F (n = 12 each) received an intrathecal administration of lidocaine 0.005 mg/ml + AGAP 25, 50, 100 μg/kg respectively. The von Frey filaments were used to assess mechanical allodynia. Nav1.7 and TRPV1 currents were recorded by the whole-cell aspiration patch-clamp technique, and KCNQ2/3 currents were recorded by the whole-cell drilling patch-clamp technique. The whole-cell aspiration patch-clamp technique showed that AGAP inhibited TRPV1and KCNQ2/3 currents and increased the analgesic effect of lidocaine. AGAP may have a synergistic effect with lidocaine which demonstrates a potential therapeutic approach for optimizing post-operative analgesia.