Painful nerve injury increases plasma membrane Ca(2+)-ATPase activity in axotomized sensory neurons

BACKGROUND: The plasma membrane Ca(2+)-ATPase (PMCA) is the principal means by which sensory neurons expel Ca(2+) and thereby regulate the concentration of cytoplasmic Ca(2+) and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca(2+) levels and activity-induced cytoplasmic Ca(2+) 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 Ca(2+) sequestration with thapsigargin, and cytoplasmic Ca(2+) concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca(2+) 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.