Impaired sensitivity to pain stimuli in plasma membrane calcium Atpase 2 (PMCA2) heterozygous mice: A possible modality- and sex-specific role for PMCA2 in nociception

Veronika Khariv, Li Ni, Ayomi Ratnayake, Sujitha Sampath, Brianna M. Lutz, Xuan Xiang Tao, Robert F. Heary, Stella Elkabes

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Plasma membrane calcium A TPase 2 (PMCA2) is a calcium pump that plays important roles in neuronal function. Although it is expressed in pain-associated regions of the CNS, including in the dorsal horn (DH), its contribution to pain remains undefined. The present study assessed the role of PMCA2 in pain responsiveness and the link between PMCA2 and glutamate receptors, GABA receptors (GABARs), and glutamate transporters that have been implicated in pain processing in the DH of adult female and male PMCA2+/+ and PMCA2+/- mice. Behavioral assays evaluated mechanical and thermal pain responsiveness. Mechanical sensitivity was significantly increased by 52% and heat sensitivity was reduced by 29% in female, but not male, PMCA2+/- mice compared with PMCA2+/+ controls. There were female-specific changes in metabotropic glutamate receptor 1,NMDA receptor 2A, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunitGluR1,GABABR1, and GABABR2 levels, whereas metabotropic glutamate receptor 5, NMDA receptor 2B, GluR2, and GABAARaα2 levels were not altered. Glutamate aspartate transporter levelswere higher and glial glutamate transporter 1 levels were lower in the DH of female, but not male, PMCA2+/- mice. These findings indicate a novel role for PMCA2 in modality- and sex-dependent pain responsiveness. Female-specific molecular changes potentially account for the altered pain responses.-Khariv, V.,Ni, L., Ratnayake, A.,Sampath, S., Lutz, B.M.,Tao, X.-X., Heary, R. F.,Elkabes, S. Impaired sensitivity to pain stimuli in plasma membrane calcium A TPase 2 (PMCA2) heterozygous mice: a possible modality and sex-specific role for PMCA2 in nociception.

Original languageEnglish (US)
Pages (from-to)224-237
Number of pages14
JournalFASEB Journal
Volume31
Issue number1
DOIs
StatePublished - Jan 2017

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Keywords

  • ATP2b2
  • GABA
  • Glutamate
  • Sensory function
  • Spinal cord

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