AI Article Synopsis

  • Mutations in the SCN11A gene, linked to neuropathic pain, have led to the creation of a mouse model (R222S) to study drug therapies for pain management.
  • The study focused on how cold exposure affects pain sensitivity in R222S mice compared to normal mice, revealing increased pain responses in the mutant strain.
  • Both acetaminophen and a traditional Japanese medicine, goshajinkigan, were found to effectively reduce pain in the R222S mice, indicating potential therapies for treating neuropathic pain related to the Na1.9 channel.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835175PMC
http://dx.doi.org/10.1007/s00210-020-01978-zDOI Listing

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