Faculty Collaboration Database

Axotomy depletes intracellular calcium stores in primary sensory neurons. Anesthesiology 2009 Aug;111(2):381-92

Date

07/16/2009

Pubmed ID

19602958

Pubmed Central ID

PMC2891519

DOI

10.1097/ALN.0b013e3181ae6212

Scopus ID

2-s2.0-68249154947 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

BACKGROUND: The cellular mechanisms of neuropathic pain are inadequately understood. Previous investigations have revealed disrupted Ca signaling in primary sensory neurons after injury. The authors examined the effect of injury on intracellular Ca stores of the endoplasmic reticulum, which critically regulate the Ca signal and neuronal function.

METHODS: Intracellular Ca levels were measured with Fura-2 or mag-Fura-2 microfluorometry in axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent L4 neurons isolated from hyperalgesic rats after L5 spinal nerve ligation, compared to neurons from control animals.

RESULTS: Endoplasmic reticulum Ca stores released by the ryanodine-receptor agonist caffeine decreased by 46% in axotomized small neurons. This effect persisted in Ca-free bath solution, which removes the contribution of store-operated membrane Ca channels, and after blockade of the mitochondrial, sarco-endoplasmic Ca-ATPase and the plasma membrane Ca ATPase pathways. Ca released by the sarco-endoplasmic Ca-ATPase blocker thapsigargin and by the Ca-ionophore ionomycin was also diminished by 25% and 41%, respectively. In contrast to control neurons, Ca stores in axotomized neurons were not expanded by neuronal activation by K depolarization, and the proportionate rate of refilling by sarco-endoplasmic Ca-ATPase was normal. Luminal Ca concentration was also reduced by 38% in axotomized neurons in permeabilized neurons. The adjacent neurons of the L4 dorsal root ganglia showed modest and inconsistent changes after L5 spinal nerve ligation.

CONCLUSIONS: Painful nerve injury leads to diminished releasable endoplasmic reticulum Ca stores and a reduced luminal Ca concentration. Depletion of Ca stores may contribute to the pathogenesis of neuropathic pain.

Author List

Rigaud M, Gemes G, Weyker PD, Cruikshank JM, Kawano T, Wu HE, Hogan QH

Author

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Axons
Axotomy
Caffeine
Calcium
Calcium Signaling
Capsaicin
Cells, Cultured
Central Nervous System Stimulants
Endoplasmic Reticulum
Hyperalgesia
Ionomycin
Ligation
Male
Nerve Degeneration
Pain Measurement
Rats
Rats, Sprague-Dawley
Ryanodine Receptor Calcium Release Channel
Sciatic Nerve
Sensory Receptor Cells
Spinal Nerves
Thapsigargin