Articles: analgesics.
-
High-impact chronic pain (HICP), defined as chronic pain with a significant impact on daily function, affects approximately 8% of the Western population. In Denmark, HICP still remains to be described at the population level. Some patients with HICP are referred to the Danish pain centres, where they are registered with a procedural code. We conducted a nationwide registry-based study of all Danish patients registered with a visit to a pain centre from January 2005 to March 2022, to explore time trends in the prescription of analgesics and sedatives in this HICP subpopulation. Furthermore, data on socioeconomics and hospital diagnoses are reported. ⋯ This nationwide study of 66,577 Danish patients with high-impact chronic pain reveals a significant decrease in filled opioid prescriptions over the past 15 years, with a simultaneous rise in gabapentinoid use before referral to pain centres. These findings suggest a shift in clinical practice towards alternative pain management strategies. The study underscores the need for continued research into the long-term effects of these changes and their impact on patient outcomes.
-
Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. ⋯ Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups.
-
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.
-
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.
-
Randomized Controlled Trial
The effect of stretching intensity on pain sensitivity: A randomized crossover study on healthy adults.
Stretching exercises have effects on local and widespread pain sensitivity. A dose-response relationship may exist between the analgesic effect and the intensity of stretching, such that a higher intensity of stretching may generate a larger reduction in analgesic response, but this remains to be studied. This study aimed to examine the dose-response relationship between stretching intensity and the analgesic effect. ⋯ The study showed a significant acute hypoalgesic effect of stretching exercises regardless of stretching intensity. This may have appropriate clinical implications for patients with musculoskeletal and nociplastic pain.