Pain
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As the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. ⋯ Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain.
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Nav1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Nav1.9, SCN11a, that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Nav1.9 has been learned through the study of rodent sensory neurons, and there is only 76% identity between human and rodent homologs of SCN11a, there is reason to suggest that there may be differences in the biophysical properties of the channels in human and rodent sensory neurons, and consequently, the contribution of these channels to the control of sensory neuron excitability, if not pain. Thus, the purpose of this study was to characterize Nav1.9 currents in human sensory neurons and compare the properties of these currents with those in rat sensory neurons recorded under identical conditions. ⋯ However, we noted a number of potentially important differences between the currents in human and rat sensory neurons including a lower threshold for activation, higher threshold for inactivation, slower deactivation, and faster recovery from slow inactivation. Human Nav1.9 was inhibited by inflammatory mediators, whereas rat Nav1.9 was potentiated. Our results may have implications for the role of Nav1.9 in sensory, if not nociceptive signaling.
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Chronic postoperative pain is present in approximately 20% of patients undergoing total knee arthroplasty. Studies indicate that pain mechanisms are associated with development and maintenance of chronic postoperative pain. The current study assessed pain sensitivity, inflammation, microRNAs, and psychological factors and combined these in a network to describe chronic postoperative pain. ⋯ The reduction of the number of parameters stabilized the models and reduced the explanatory value to 69% and 51%. This is the first study to use the DIABLO model for chronic postoperative pain and to demonstrate how different pain mechanisms form a pain mechanistic network. The complex model explained 81% of the variability of clinical pain intensity, whereas the less complex model explained 51% of the variability of clinical pain intensity.
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Chronic postsurgical pain (CPSP) is a highly prevalent condition. To improve CPSP management, we aimed to develop and internally validate generalizable point-of-care risk tools for preoperative and postoperative prediction of CPSP 3 months after surgery. A multicentre, prospective, cohort study in adult patients undergoing elective surgery was conducted between May 2021 and May 2023. ⋯ These models demonstrated good calibration and clinical utility. The primary CPSP model demonstrated fair predictive performance including 2 significant predictors. Derivation of a generalizable risk tool with point-of-care predictors was possible for the threshold-based CPSP models but requires independent validation.