Pharmacology/Drug Development

Acute low back pain (LBP) is a common condition that can be chronic if not properly treated. Aceclofenac and eperisone hydrochloride are commonly prescribed drugs for acute LBP and muscle spasms. Therefore, NVP-1203, a fixed-dose combination of 100 mg aceclofenac and 75 mg eperisone hydrochloride, is being developed. This study aimed to evaluate the efficacy and safety of NVP-1203 compared to those of a single administration of 100 mg aceclofenac in patients with acute LBP and muscle spasms.

Corporations across sectors engage in the conduct, sponsorship, and dissemination of scientific research. Industry sponsorship of research, however, is associated with research agendas, outcomes, and conclusions that are favourable to the sponsor. The legalization of cannabis in Canada provides a useful case study to understand the nature and extent of the nascent cannabis industry's involvement in the production of scientific evidence as well as broader impacts on equity-oriented research agendas. We conducted a cross-sectional, descriptive, meta-research study to describe the characteristics of research that reports funding from, or author conflicts of interest with, Canadian cannabis companies. From May to August 2021, we sampled licensed, prominent Canadian cannabis companies, identified their subsidiaries, and searched each company name in the PubMed conflict of interest statement search interface. Authors of included articles disclosed research support from, or conflicts of interest with, Canadian cannabis companies. We included 156 articles: 82% included at least one author with a conflict of interest and 1/3 reported study support from a Canadian cannabis company. More than half of the sampled articles were not cannabis focused, however, a cannabis company was listed amongst other biomedical companies in the author disclosure statement. For articles with a cannabis focus, prevalent topics included cannabis as a treatment for a range of conditions (15/72, 21%), particularly chronic pain (6/72, 8%); as a tool in harm reduction related to other substance use (10/72, 14%); product safety (10/72, 14%); and preclinical animal studies (6/72, 8%). Demographics were underreported in empirical studies with human participants, but most included adults (76/84, 90%) and, where reported, predominantly white (32/39, 82%) and male (49/83, 59%) participants. The cannabis company-funded studies included people who used drugs (37%) and people prescribed medical cannabis (22%). Canadian cannabis companies may be analogous to peer industries such as pharmaceuticals, alcohol, tobacco, and food in the following three ways: sponsoring research related to product development, expanding indications of use, and supporting key opinion leaders. Given the recent legalization of cannabis in Canada, there is ample opportunity to create a policy climate that can mitigate the harms of criminalization as well as impacts of the "funding effect" on research integrity, research agendas, and the evidence base available for decision-making, while promoting high-priority and equity-oriented independent research.

To describe patient characteristics, treatment patterns, and the burden of illness among adult migraine patients in Canada prescribed migraine prophylactics. Little is known about the relative persistence of treatments in the real-world setting and the impact of migraine prophylactic therapy on patients. As a result, migraine care in Canada continues to inadequately serve patients suffering from frequent headache days, reflecting a large unmet need.

The κ-opioid receptor (KOR) has recently emerged as an alternative therapeutic target for the development of pain medications, without deleterious side effects associated with the μ-opioid receptor (MOR). However, modulation of KOR is currently under investigation for the treatment of depression, mood disorders, psychiatric comorbidity, and specific drug addictions. However, KOR agonists also trigger adverse effects including sedation, dysphoria, and hallucinations. In this respect, there is currently much debate on alternative paradigms. Recent effort has been devoted in search of biased ligands capable of selectively activating favorable signaling over signaling associated with unwanted side effects. On the other hand, the use of partial agonists is expected to allow the analgesia to be produced at dosages lower than those required to produce the adverse effects. More empirically, the unwanted central effects can be also avoided by using peripherally restricted agonists. In this review, we discuss the more recent trends in the design of KOR-selective, biased or partial, and finally, peripherally acting agonists. Special emphasis is given on the discussion of the most recent approaches for controlling functional selectivity of KOR-specific ligands.

Migraine is a chronic neurological disorder that affects approximately 12% of the population. The cause of migraine headaches is not yet known, however, when the trigeminal system is activated, neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP) are released, which cause neurogenic inflammation and sensitization. Advances in the understanding of migraine pathophysiology have identified new potential pharmacological targets. In recent years, transient receptor potential (TRP) channels have been the focus of attention in the pathophysiology of various pain disorders, including primary headaches. Genetic and pharmacological data suggest the role of TRP channels in pain sensation and the activation and sensitization of dural afferents. In addition, TRP channels are widely expressed in the trigeminal system and brain regions which are associated with the pathophysiology of migraine and furthermore, co-localize several neuropeptides that are implicated in the development of migraine attacks. Moreover, there are several migraine trigger agents known to activate TRP channels. Based on these, TRP channels have an essential role in migraine pain and associated symptoms, such as hyperalgesia and allodynia. In this review, we discuss the role of the certain TRP channels in migraine pathophysiology and their therapeutic applicability.

To perform a systematic review of real-world outcomes for anti-CGRP-mAbs.

Endometriosis is a chronic inflammatory disease associated with pelvic pain, infertility, and increased cardiovascular risk. Recent studies suggest a possible role of aldosterone as a pro-inflammatory hormone in the pathogenesis of the disease. Cortisol is also an important mediator of stress reaction, but its role is controversial in endometriosis. The aim of this study was to evaluate aldosterone and cortisol levels and blood pressure values in women with endometriosis. We measured blood pressure, plasma aldosterone, renin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) in 20 women with untreated minimal or mild pelvic endometriosis compared with 20 healthy controls matched for age and body mass index. Aldosterone values were similar in the two groups, while renin was significantly lower and the aldosterone to renin ratio was significantly higher in patients with endometriosis than in controls. Systolic blood pressure was in the normal range, but significantly higher in patients with endometriosis. Morning plasma cortisol was normal, but significantly lower in patients with endometriosis compared with controls, while DHEAS to cortisol ratio was similar in the two groups. These preliminary results are evidence of increased biological aldosterone activity and dysregulation of the hypothalamic-pituitary-adrenal axis in early stages of endometriosis. These alterations could play a role in disease development, suggesting new therapeutic targets for aldosterone receptor blockers.

The management of orofacial pain to alleviate the quality of life of affected patients is becoming increasingly challenging for scientific research and healthcare professionals. From this perspective, in addition to conventional therapies, new alternatives are being sought, increasingly looking at the use of both natural and synthetic products. L. represents an interesting source of bioactive compounds, including non-psychoactive cannabinoids, flavonoids, and terpenes, many of which are effective in improving pain intensity. Here, we aim to analyze the possible mechanisms of action of the bioactive natural and synthetic hemp-derived compounds responsible for the modulatory effects on pain-related pathways. The ability of these compounds to act on multiple mechanisms through a synergistic effect, reducing both the release of inflammatory mediators and regulating the response of the endocannabinoid system, makes them interesting agents for alternative formulations to be used in orofacial pain.