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Papers of the Week


Papers: 20 Jun 2020 - 26 Jun 2020


Animal Studies


2020 Jun 15


Pain

Loss of SLC9A6/NHE6 impairs nociception in a mouse model of Christianson Syndrome.

Authors

Petitjean H, Fatima T, Mouchbahani-Constance S, Davidova A, Ferland CE, Orlowski J, Sharif-Naeini R
Pain. 2020 Jun 15.
PMID: 32569089.

Abstract

Children diagnosed with Christianson Syndrome (CS), a rare X-linked neurodevelopmental disorder characterized by intellectual disability, epilepsy, ataxia and mutism, also suffer from hyposensitivity to pain. This places them at risk of sustaining serious injuries that often go unattended. CS is caused by mutations in the alkali cation/proton exchanger SLC9A6/NHE6 that regulates recycling endosomal pH homeostasis and trafficking. Yet it remains unclear how defects in this transporter lead to altered somatosensory functions. In this study, we validated a Nhe6 knockout (KO) mouse as a model of CS and used it to identify the cellular mechanisms underlying the elevated pain tolerance observed in CS patients. Within the central nervous system, NHE6 immunolabelling is detected in a small percentage of cortical neurons involved in pain processing, including those within the primary somatosensory and the anterior cingulate cortices as well as the periaqueductal grey. Interestingly, it is expressed in a larger percentage of nociceptors. Behaviourally, Nhe6 KO mice have decreased nocifensive responses to acute noxious thermal, mechanical and chemical (i.e., capsaicin) stimuli. The reduced capsaicin-sensitivity in the KO mice correlates with a decreased expression of the transient receptor potential channel TRPV1 at the plasma membrane and capsaicin-induced Ca influx in primary cultures of nociceptors. These data indicate that NHE6 is a significant determinant of nociceptor function and pain behaviours, vital sensory processes that are impaired in CS.