Pharmacology/Drug Development

Increasing attention has been attracted to the development of bifunctional compounds to minimize the side effects of opioid analgesics. Pharmacological studies have verified the functional interaction between opioid and cannabinoid systems in pain management, suggesting that coactivation of the opioid and cannabinoid receptors may provide synergistic analgesia with fewer adverse reactions. Herein, we developed and characterized a novel bifunctional compound containing the pharmacophores of the mu-opioid receptor agonist DALDA and the cannabinoid peptide VD-Hpα-NH2, named OCP002.

Tissue injuries, including burns, are major causes of death and morbidity worldwide. These injuries result in the release of intracellular molecules and subsequent inflammatory reactions, changing the tissues' chemical milieu and leading to the development of persistent pain through activating pain-sensing primary sensory neurons. However, the majority of pain-inducing agents in injured tissues are unknown. Here, we report that, amongst other important metabolite changes, lysophosphatidylcholines (LPCs) including 18:0 LPC exhibit significant and consistent local burn injury-induced changes in concentration. 18:0 LPC induces immediate pain and the development of hypersensitivities to mechanical and heat stimuli through molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1, and member 2 at least partly via increasing lateral pressure in the membrane. As levels of LPCs including 18:0 LPC increase in other tissue injuries, our data reveal a novel role for these lipids in injury-associated pain. These findings have high potential to improve patient care.

The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain.

Patients with life-limiting cancers are commonly prescribed opioids to manage pain, dyspnea, and cough. Proper prescription opioid disposal is essential to prevent poisonings and deaths. We examined opioid disposal practices of patients referred to a Canadian outpatient palliative care clinic (OPCC). The primary objective was to determine the prevalence of OPCC patients who did not routinely dispose their opioids. The secondary objectives were to examine their methods of opioid disposal and to identify patient characteristics associated with routine disposal of opioids. This cross-sectional study involved a retrospective chart review of new, adult patients who were seen in a Canadian OPCC (September 2018-August 2019) and completed a survey about opioid-related constructs: source of prescriptions, use, storage, disposal, and knowledge about associated harms. Among the 122 study participants, half (58/111, 52.3%) reported that they did not routinely dispose their opioids. The most common method of disposal was by giving them to pharmacists (69/88, 78.4%). Cannabis use (odds ratio [OR]: 3.7, 95% confidence interval [CI]: 1.1-11.8) and neuropathic medication use (OR: 3.0, 95% CI: 1.2-7.2) were positively associated with routine disposal of opioids. Conversely, reports of an increased amount of opioid use in the past six months were negatively associated with routine disposal of opioids (OR: 0.38, 95% CI: 0.16-0.88). The high prevalence of people with life-limiting illnesses who do not routinely dispose their opioids requires increased attention. Interventions, such as education, are needed to reduce medication waste and opioid-related harms.

To assess long-term safety, tolerability, and efficacy of once-daily oral atogepant 60 mg in adults with migraine.

Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.

Cannabinoids represent a promising therapeutic avenue for chronic pain, however clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition of voltage-gated calcium channels is one mechanism through which cannabinoids may produce analgesia. We hypothesized that cannabinoids and cannabinoid receptor agonists target different types of voltage gated calcium channels through distinct mechanisms.

and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS). Whereas the analgesic effect of PAP has been attributed to a local effect on the mucosa of the lower urinary tract (LUT), the molecular targets of PAP remain unknown. We investigated the effect of PAP on pain-related Transient Receptor Potential (TRP) channels expressed in sensory neurons that innervate the bladder wall.

Expectations of patients influence the perception and neuronal processing of acute and chronic pain and modulate the effectiveness of analgesic treatment. The expectation of treatment is not only the most important determinant of placebo analgesia. Expectations of treatment also influence the efficacy and tolerability of "active" pharmacological and non-pharmacological treatment of pain. Recent insights into the psychological and neurobiological mechanisms underlying the clinically relevant effects of treatment expectations enable and call for the systematic integration and modulation of treatment expectations into analgesic treatment concepts. Such a strategy promises to optimize analgesic treatment and to prevent or reduce the burden of unwanted side effects and the misuse of analgesics, particularly of opioids. This review highlights the current concepts, recent achievements and also challenges and key open research questions.

A wastewater-based epidemiology (WBE) method is presented to estimate analgesic consumption and assess the burden of treated pain in Australian communities. Wastewater influent samples from 60 communities, representing ∼52% of Australia's population, were analyzed to quantify the concentration of analgesics used to treat pain and converted to estimates of the amount of drug consumed per day per 1000 inhabitants using pharmacokinetics and WBE data. Consumption was standardized to the defined daily dose per day per 1000 people. The population burden of pain treatment was classified as mild to moderate pain (for non-opioid analgesics) and strong to severe pain (for opioid analgesics). The mean per capita weighted total DDD of non-opioid analgesics was 0.029 DDD/day/person, and that of opioid-based analgesics was 0.037 DDD/day/person across Australia. A greater burden of pain (mild to moderate or strong to severe pain index) was observed at regional and remote sites. The correlation analysis of pain indices with different socioeconomic descriptors revealed that pain affects populations from high to low socioeconomic groups. Australians spent an estimated US $3.5 (AU $5) per day on analgesics. Our findings suggest that WBE could be an effective surveillance tool for estimating the consumption of analgesics at a population scale and assessing the total treated pain burden in communities.