Acid-Sensing Ion Channels (ASICs): Pharmacology and implication in pain

被引:238
作者
Deval, Emmanuel [1 ]
Gasull, Xavier [1 ,2 ]
Noel, Jacques [1 ]
Salinas, Miguel [1 ]
Baron, Anne [1 ]
Diochot, Sylvie [1 ]
Lingueglia, Eric [1 ]
机构
[1] Univ Nice Sophia Antipolis UNS, CNRS, UMR 6097, IPMC, F-06560 Valbonne, France
[2] Univ Barcelona, IDIBAPS, Fac Med, Neurophysiol Lab, E-08036 Barcelona, Spain
关键词
Pain; Nociception; Acid; Ion channels; ASIC; Neurons; DORSAL-ROOT GANGLIA; GATED CATION CHANNEL; TARANTULA TOXIN PSALMOTOXIN-1; EXPERIMENTAL TISSUE ACIDOSIS; SENSORY NEURON EXCITABILITY; BRAIN NA+ CHANNEL; INFLAMMATORY PAIN; SODIUM-CHANNEL; SENSITIVE CHANNELS; CAPSAICIN RECEPTOR;
D O I
10.1016/j.pharmthera.2010.08.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tissue acidosis is a common feature of many painful conditions. Protons are indeed among the first factors released by injured tissues, inducing a local pH fall that depolarizes peripheral free terminals of nociceptors and leads to pain. ASICs are excitatory cation channels directly gated by extracellular protons that are expressed in the nervous system. In sensory neurons, they act as "chemo-electrical" transducers and are involved in somatic and visceral nociception. Two highly specific inhibitory peptides isolated from animal venoms have considerably helped in the understanding of the physiological roles of these channels in pain. At the peripheral level, ASIC3 is important for inflammatory pain. Its expression and its activity are potentiated by several pain mediators present in the "inflammatory soup" that sensitize nociceptors. ASICs have also been involved in some aspects of mechanosensation and mechanonociception, notably in the gastrointestinal tract, but the underlying mechanisms remain to be determined. At the central level, ASIC1a is largely expressed in spinal cord neurons where it has been proposed to participate in the processing of noxious stimuli and in central sensitization. Blocking ASIC1a in the spinal cord also produces a potent analgesia in a broad range of pain conditions through activation of the opiate system. Targeting ASIC channels at different levels of the nervous system could therefore be an interesting strategy for the relief of pain. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:549 / 558
页数:10
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