Painful nerve injury increases plasma membrane Ca2+-ATPase activity in axotomized sensory neurons

Geza Gemes, Katherine D. Oyster, Bin Pan, Hsiang En Wu, Madhavi Latha Y. Bangaru, Qingbo Tang, Quinn H. Hogan

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Background: The plasma membrane Ca2+-ATPase (PMCA) is the principal means by which sensory neurons expel Ca2+ and thereby regulate the concentration of cytoplasmic Ca2+ and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca2+ levels and activity-induced cytoplasmic Ca2+ accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain.Results: PMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca2+ sequestration with thapsigargin, and cytoplasmic Ca2+ concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca2+ transients resolved was increased in axotomized neurons after spinal nerve ligation, indicating accelerated PMCA function. Electrophysiological recordings showed that blockade of PMCA by vanadate prolonged the action potential afterhyperpolarization, and also decreased the rate at which neurons could fire repetitively.Conclusion: We found that PMCA function is elevated in axotomized sensory neurons, which contributes to neuronal hyperexcitability. Accelerated PMCA function in the primary sensory neuron may contribute to the generation of neuropathic pain, and thus its modulation could provide a new pathway for peripheral treatment of post-traumatic neuropathic pain.

Original languageEnglish (US)
Article number46
JournalMolecular pain
Volume8
DOIs
StatePublished - Jun 19 2012
Externally publishedYes

Keywords

  • Calcium
  • Dorsal root ganglion
  • Nerve injury
  • Neuron
  • PMCA

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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