Articles: analgesics.
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Opioid analgesics are commonly used to treat acute and chronic pain following traumatic injury. Psychiatric comorbidity has been reported to be associated with increased pain and persistent opioid use. Our aims were to determine the extent of post-injury opioid use and assess whether pre-injury antidepressant, benzodiazepine, and z-hypnotic drug use is associated with increased post-injury opioid use. ⋯ This large registry-based study adds to the body of knowledge on opioid use beyond in-hospital care in patients having sustained traumatic injury, a field which is scarcely investigated and not yet fully understood. It suggests that both previous drug therapy and the nature of opioid treatment initiation may affect outcome. This will help guide clinicians in selecting the appropriate pain management in this patient group.
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Voltage-gated sodium (Na v ) channels present untapped therapeutic value for better and safer pain medications. The Na v 1.8 channel isoform is of particular interest because of its location on peripheral pain fibers and demonstrated role in rodent preclinical pain and neurophysiological assays. To-date, no inhibitors of this channel have been approved as drugs for treating painful conditions in human, possibly because of challenges in developing a sufficiently selective drug-like molecule with necessary potency not only in human but also across preclinical species critical to the preclinical development path of drug discovery. ⋯ In this report, we have leveraged numerous physiological end points in nonhuman primates to evaluate the analgesic and pharmacodynamic activity of a novel, potent, and selective Na v 1.8 inhibitor compound, MSD199. These pharmacodynamic biomarkers provide important confirmation of the in vivo impact of Na v 1.8 inhibition on peripheral pain fibers in primates and have high translational potential to the clinical setting. These findings may thus greatly improve success of translational drug discovery efforts toward better and safer pain medications, as well as the understanding of primate biology of Na v 1.8 inhibition broadly.
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The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of G i/o -coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. ⋯ Consistent with this mechanism of action, we confirmed that TRPA1-mediated colonic contractions evoked by SP release were abolished by CS pretreatment in a GPR35-dependent manner. Our data demonstrate that GPR35 agonists prevent the activation and sensitisation of colonic nociceptors through the inhibition of TRPA1-mediated SP release. These findings highlight the potential of GPR35 agonists to deliver nonopioid analgesia for the treatment of abdominal pain.
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To evaluate the impact of persistent opioid use (POU) following surgery or trauma on health outcomes using linked data. ⋯ Among opioid-naive patients who received opioids after surgery or trauma, POU was associated with worse outcomes, including increased mortality. Further investigation is warranted to understand the reasons for continued opioid use beyond 90 days and mechanisms associated with harm.
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Pain is common during pregnancy yet there are few contemporary studies of opioid utilisation in pregnancy. We aimed to describe prescription analgesic opioid use during pregnancy across four regions: Oceania [New South Wales (Australia), New Zealand], North America [Ontario (Canada), United States (US)], Northern Europe [Denmark, Finland, Iceland, Norway, Sweden, United Kingdom (UK)], and East Asia (Hong Kong, South Korea, Taiwan). ⋯ In this large multinational study, we observed wide global variation in prevalence of analgesic opioid use in pregnancy, yet patterns of use by sociodemographic- and pregnancy characteristics were relatively consistent. Analgesic opioid use remained stable or downward trending over time in most, but not all, countries.