Painful nerve injury increases plasma membrane Ca2 -ATPase activity in axotomized sensory neuronsReport as inadecuate




Painful nerve injury increases plasma membrane Ca2 -ATPase activity in axotomized sensory neurons - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 8:46

First Online: 19 June 2012Received: 05 April 2012Accepted: 13 June 2012

Abstract

BackgroundThe plasma membrane Ca-ATPase PMCA is the principal means by which sensory neurons expel Ca and thereby regulate the concentration of cytoplasmic Ca and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca levels and activity-induced cytoplasmic Ca accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain.

ResultsPMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca sequestration with thapsigargin, and cytoplasmic Ca concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca 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.

ConclusionWe 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.

KeywordsPMCA Dorsal root ganglion Neuron Calcium Nerve injury Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-46 contains supplementary material, which is available to authorized users.

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Author: Geza Gemes - Katherine D Oyster - Bin Pan - Hsiang-En Wu - Madhavi Latha Yadav Bangaru - Qingbo Tang - Quinn H Hogan

Source: https://link.springer.com/







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