Pain
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Chronic pain is common among children and adolescents; however, the diagnoses in the newly developed 11th revision of the International Classification of Diseases (ICD-11) chronic pain chapter are based on adult criteria, overlooking pediatric neurodevelopmental differences. The chronic pain diagnoses have demonstrated good clinical applicability in adults, but to date, no field study has examined these diagnoses to the most specific diagnostic level in a pediatric sample. The current study aimed to explore pediatric representation within the ICD-11, with focus on chronic primary pain. ⋯ The latter also exhibited the lowest agreement between HCPs and algorithm. The current study underscores the need for evidence-based improvements to the ICD-11 diagnostic criteria in pediatrics. Developing pediatric coding notes could improve the visibility of patients internationally and improve the likelihood of receiving reimbursement for necessary treatments through accurate coding.
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Translational models of the sensitized pain system are needed to progress the understanding of involved mechanisms. In this study, long-term potentiation was used to develop a mechanism-based large-animal pain model. Event-related potentials to electrical stimulation of the ulnar nerve were recorded by intracranial recordings in pigs, 3 weeks before, immediately before and after, and 3 weeks after peripheral high-frequency stimulation (HFS) applied to the ulnar nerve in the right forelimb (7 pigs) or in control animals (5 pigs). ⋯ The relative increase in N1 30 minutes after HFS and the degree of mechanical hyperalgesia 2 weeks post-HFS was correlated ( P < 0.033). These results show for the first time that the pig HFS model resembles the human HFS model closely where the profile of sensitization is comparable. Interestingly, the degree of sensitization was associated with the cortical signs of hyperexcitability at HFS induction.
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Na v 1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Na v 1.9, SCN11a , that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Na v 1.9 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 Na v 1.9 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 Na v 1.9 was inhibited by inflammatory mediators, whereas rat Na v 1.9 was potentiated. Our results may have implications for the role of Na v 1.9 in sensory, if not nociceptive signaling.
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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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Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). ⋯ Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.