Download Calcium is a universal second messenger, and changes in

Calcium signaling in nociceptive neurons in normal and pathological conditions.
Dr. Nana Voitenko
Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology,
Kiev, Ukraine
Calcium is a universal second messenger, and changes in the intracellular cytosolic Ca2+
concentration ([Ca2+]i) triggers a wide spectrum of cellular responses including a long-lasting
modification of synaptic transmission and changes in cellular excitability and gene expression that
may lead to changes in the transmission of nociceptive stimuli. The intracellular calcium stores,
such as ER and mitochondria together with plasma membrane calcium regulating systems, play a
key role in shaping neuronal calcium signalling. It is also becoming clear that Ca2+ might play a
signalling role not only in cytoplasm but also in the ER where it regulates synthesis of proteins,
their chaperoning and activation of calcium influx via capacitative calcium entry. What seems to be
even more important is that recent evidence suggests an extreme importance of the ER as a calcium
store and sink in fast processes occurring during synaptic transmission as well as in plasticity of the
transmission in central nervous system. Thus, it is becoming apparent that impaired calcium
homeostasis both in the cytosol and lumen of the ER could be a common step in many
neurodegenerative disorders leading to changes in nociceptive signalling.
In most neuronal cells in central and peripheral nervous systems, calcium signaling is
initiated by the activation of plasma membrane calcium channels or calcium-releasing channels
(inositoltrisphosphate and ryanodine receptors) located in the membrane of the ER. An abnormal
activity of plasma membrane calcium channel and the ER calcium regulation has been described in
primary and secondary sensory neurons, and has been already implicated in the pathogenesis of
neuropathic and inflammatory disorders.
It has been shown in recent works originating from different laboratories (including ours)
that experimental pain conditions (including peripheral inflammation, nerve injury and diabetic
neuropathy) do induce significant changes in cytosolic [Ca2+]i homeostasis in both dorsal root
ganglion (DRG) and dorsal horn (DH) neurons - neurons participating in transmission of
nociceptive signals. These changes include a steady-state increase in resting cytosolic Ca2+
concentration, a decrease in the amplitude of depolarization- and neuromediator-induced [Ca2+]i
signals, prolongation of the recovery time of [Ca2+]i transients, up- and down-regulation of Ca2+
entry via plasma membrane calcium channels, considerable changes in the efficacy of functioning
of intracellular calcium stores such as mitochondria and the ER. Results of several recent studies
prove that diabetic neuropathy leads to a significant decrease of Ca2+ release from intracellular
stores both in DRG and DH neurons suggesting altered ER Ca2+ handling and possible reduction in
the amount of releasable Ca2+ within the ER lumen.
Thus, changes in [Ca2+]i regulation in primary and secondary sensory neurons may be a
common basis for abnormal nociceptive signalling during various types of diseases and pain
syndromes.