Mutations within the SCN11A gene which encodes the voltage-gated sodium channel Na1.9 mainly expressed in small fiber sensory neurons have been associated with neuropathic disorders; however, suitable medications have not been fully investigated. To develop drug therapies against Na1.9-related neuropathic pain, we aimed to establish a novel model using mice carrying the Scn11a p.R222S mutation initially identified in patients with familial episodic limb pain that is characterized by paroxysmal pain induced by fatigue or bad weather conditions. We investigated the influence of cold exposure (4 °C, overnight) on the behavioral and biochemical phenotypes of Scn11a p.R222S mutant (R222S) and wild type C57BL/6N (WT) mice. We also tested the effects of acetaminophen (125, 250 mg/kg, perorally, p.o.) and traditional Japanese medicine, goshajinkigan (0.5 or 1.0 g/kg, p.o.), which are analgesic drugs prescribed to patients with neuropathic pain, in this model of cold-induced mechanical allodynia in R222S mice.Cold-exposed R222S mice exhibited enhanced mechanical allodynia and thermal hypersensitivity compared with WT mice. The decrease of the mechanical withdrawal threshold in R222S mice was reversible 24 h after housing at room temperature. There was no significant change in the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, or interferon-γ in the plasma or spinal cords of WT and R222S mice after cold exposure. Both acetaminophen (250 mg/kg) and goshajinkigan (1.0 g/kg) significantly attenuated mechanical allodynia in R222S mice. The model of cold-induced mechanical allodynia in mice with the Scn11a p.R222S mutation is novel and useful for evaluating analgesic drugs for intractable neuropathies related to Na1.9.
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http://dx.doi.org/10.1007/s00210-020-01978-z | DOI Listing |
CNS Neurosci Ther
January 2025
School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Aims: N-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.
Methods: We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models.
Sci Rep
January 2025
Department of Biosciences, Universidade Estadual de Campinas (UNICAMP), Faculdade de Odontologia de Piracicaba (FOP), Piracicaba, Brazil.
This study compared the degree of secondary hyperalgesia and somatosensory threshold changes induced by topical capsaicin between spinal and trigeminal innervation. This crossover clinical trial included 40 healthy individuals in which 0.25 g of 1% capsaicin cream was randomly applied for 45 minutes to a circular area of 2 cm to the skin covering the masseter muscle and forearm in 2 different sessions, separated by at least 24 hours and no more than 72 hours (washout period).
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China.
Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients' quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we present a spatially confined conduit strategy, designed to enhance the self-organization of regenerating nerves after truncation.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Pharmacy, International Institute of Science, Arts, and Technology (IISAT), Gujranwala, Pakistan.
Background: Cancer remains a predominant cause of death worldwide. The advent of effective chemotherapy has enormously decreased the mortality rate and increased the life expectancy of cancer patients. However, the adverse effects allied with chemotherapy contribute to the development of neurotoxicity, anxiety, and depression.
View Article and Find Full Text PDFKorean J Pain
January 2025
Department of Anesthesiology and Pain Medicine and Anesthesia & Pain Research Institute, Yonsei University Medical College, Seoul, Korea.
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