Abstract
The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord. This function of nociceptors relies on the coordinated operation of a variety of ion channels. In this review, we summarize how members of nine different families of ion channels expressed in sensory neurons contribute to nociception. Furthermore, data on 35 different types of G protein coupled receptors are presented, activation of which controls the gating of the aforementioned ion channels. These receptors are not only targeted by more than 20 separate endogenous modulators, but can also be affected by pharmacotherapeutic agents. Thereby, this review provides information on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.
Highlights
Nociception refers to “neural processes of encoding and processing noxious stimuli” as defined by the International Association for the Study of Pain
The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord
The present review summarizes signaling mechanisms that link an activation of G protein-coupled receptor (GPCR) to changes in ion channel function in nociceptors
Summary
Nociception refers to “neural processes of encoding and processing noxious stimuli” as defined by the International Association for the Study of Pain. Apart from acting directly on nociceptors, such injurious impact may lead to inflammation, as do infections This pathologic response is characterized by the release of a plethora of mediators from various types of cells including, amongst others, macrophages, mast cells, immune cells, platelets and the nociceptive neurons themselves [2]. Constituents of the inflammatory soup comprise protons, nucleotides and nucleosides, enzymes (proteases), fatty acid derivatives (prostanglandins), biogenic amines (histamine, noradrenaline, and serotonin), cytokines, chemokines, neurotrophins and other peptides (bradykinin, endothelin, and tachykinins) [3] These multifarious endogenous agents influence nociceptor signaling through a variety of different receptors:. Sensitization means that this transformation of noxious stimuli into action potentials is facilitated, and this may occur through one of two possible mechanisms: reduction in the action potential threshold or increased responses to suprathreshold stimuli In principle, these two pathophysiological alternatives underlie the clinical phenomena of allodynia and hyperalgesia, respectively [1]. For the sake of comprehensiveness, such inhibitory receptors are considered as well
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