title: 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.
abstract: Plasma membrane calcium ATPase 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, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1, GABABR1, and GABABR2 levels, whereas metabotropic glutamate receptor 5, NMDA receptor 2B, GluR2, and GABAARα2 levels were not altered. Glutamate aspartate transporter levels were 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 ATPase 2 (PMCA2) heterozygous mice: a possible modality- and sex-specific role for PMCA2 in nociception.
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.|Graduate School of Biomedical Sciences, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Khariv
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Ayomi
authors.initials: A
authors.lastname: Ratnayake
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Sujitha
authors.initials: S
authors.lastname: Sampath
authors.affiliation: Graduate School of Biomedical Sciences, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.|Department of Anesthesiology, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA; and.
authors.forename: Brianna M
authors.initials: BM
authors.lastname: Lutz
authors.affiliation: Department of Anesthesiology, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA; and.
authors.forename: Xuan-Xiang
authors.initials: XX
authors.lastname: Tao
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Heary
authors.affiliation: Department of Neurological Surgery, The Reynolds Family Spine Laboratory, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA; elkabest@njms.rutgers.edu.
authors.forename: Stella
authors.initials: S
authors.lastname: Elkabes
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D020886:Somatosensory Disorders / Q000235:genetics / Q000378:metabolism*
chemical_list: D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse
keywords: ATP2b2; GABA; glutamate; sensory function; spinal cord