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Papers of the Week

Papers: 19 Sep 2020 - 25 Sep 2020

Animal Studies

2020 Sep 24

Naunyn Schmiedebergs Arch Pharmacol

Mechanical allodynia triggered by cold exposure in mice with the Scn11a p.R222S mutation: a novel model of drug therapy for neuropathic pain related to Na1.9.


Matsubara Y, Okuda H, Harada KH, Youssefian S, Koizumi A
Naunyn Schmiedebergs Arch Pharmacol. 2020 Sep 24.
PMID: 32970203.


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.