Acid-Sensing Ion Channels in Postoperative Pain

Deval, Emmanuel; Noël, Jacques; Gasull, Xavier; Delaunay, A; Alloui, Abdelkrim; Friend, Valérie; Eschalier, Alain; Lazdunski, Michel; Lingueglia, Éric

doi:10.1523/jneurosci.5266-10.2011

Cited by 154 publications

(158 citation statements)

References 46 publications

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“…The use of APETx2 in vivo has been key in establishing the role of ASIC3 as a sensor of acid-induced and post-operative pain (Deval et al, 2011), and demonstrating its involvement in inflammatory pathways (Deval et al, 2008). In agreement with this, several independent labs have reported that APETx2 is analgesic in rat models of inflammatory and osteoarthritic pain (Deval et al, 2008;Ikeuchi et al, 2009;Karczewski et al, 2010).…”

Section: Apetx2 In Peripheral Painmentioning

confidence: 80%

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Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms

Cristofori-Armstrong

Rash

2017

Neuropharmacology

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Please cite this article as: Cristofori-Armstrong, B., Rash, L.D., Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms, Neuropharmacology (2017), doi: 10.1016/j.neuropharm.2017.04.042. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT2 ABSTRACT Acid-sensing ion channels (ASICs) are proton-activated cation channels that are expressed in a variety of neuronal and non-neuronal tissues. As proton-gated channels, they have been implicated in many pathophysiological conditions where pH is perturbed. Venom derived compounds represent the most potent and selective modulators of ASICs described to date, and thus have been invaluable as pharmacological tools to study ASIC structure, function, and biological roles. There are now ten ASIC modulators described from animal venoms, with those from snakes and spiders favouring ASIC1, while the sea anemones preferentially target ASIC3. Some modulators, such as the prototypical ASIC1 modulator PcTx1 have been studied in great detail, while some of the newer members of the club remain largely unstudied. Here we review the current state of knowledge on venom derived ASIC modulators, with a particular focus on their molecular interaction with ASICs, what they have taught us about channel structure, and what they might still reveal about ASIC function and pathophysiological roles.

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Section: Apetx2 In Peripheral Painmentioning

confidence: 80%

“…The peptide is slightly less potent on the human ASIC3 subtype with an IC 50 of 175 nM. APETx2 inhibits the typical transient acid-induced current and the pH 7.0 evoked window (sustained) current of ASIC3 (Deval et al, 2011), as M A N U S C R I P T…”

Section: The First Selective Asic3 Inhibitormentioning

confidence: 99%

Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms

Cristofori-Armstrong

Rash

2017

Neuropharmacology

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“…The results demonstrated that gabapentinoids might significantly attenuate the neuropathic pain behaviour in both animal models of peripheral neuropathy. The mechanisms of post-incisional nociception are distinct from those of other pain conditions [16]. Acute gabapentin (60 mg/kg) treatment was found to markedly alleviate thermal hyperalgesia in incision model of postoperative pain in diabetic rats.…”

Section: Experimental Neuropathic Pain In Ratsmentioning

confidence: 91%

Preclinic and clinic effectiveness of gabapentin and pregabalin for treatment of neuropathic pain in rats and diabetic patients

Surcheva

Todorova

Maslarov

et al. 2017

Biotechnology & Biotechnological Equipment

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Pregabalin and gabapentin are amino-acid derivatives of gamma-aminobutyric acid. They have a high affinity to the a2d protein in the central nervous system and both have been shown to be effective for neuropathic pain disorder. The aim of this study was to investigate the efficacy of gabapentin and pregabalin in animal models of neuropathic pain, and to correlate with clinical outcomes in patients with diabetic neuropathy. Gabapentin (60 mg/kg) and pregabalin (30 mg/kg) attenuate mechanical, tactile and heat hypersensitivity in rats with chronic constriction injury of the sciatic nerve and streptozotocin (STZ)-induced diabetes. There is no evidence that one of the drugs is superior to another at the different rat models and tests. In the incisional pain model, there was partial efficacy of gabapentin. Our clinical data suggest that relative to the baseline pain score, the treatment with pregabalin at doses of 300 mg/day or gabapentin at doses of 900 mg/day would be effective and well tolerated in patients diagnosed with moderate diabetic polyneuropathy. The study suggested that pregabalin may provide better analgesic outcomes than gabapentin on the sixth month of treatment. In conclusion, the comparative effects of gabapentinoids in animal models of neuropathic pain and neuropathic patients are suggestive of similar pathophysiological mechanisms being involved, but successful outcome is determined by a patient's individuality and the drug nature as well as the drug tolerability.

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“…All these properties have been proposed to be important for the role of ASIC3 in pain (16,20,21). Peripheral ASIC3-containing channels have been shown (i) to participate to acidic, inflammatory, and postoperative pain (16,22,23); (ii) to contribute to primary and/or secondary mechanical hyperalgesia in muscles and joints after inflammation or injury (3,24,25); (iii) to be involved in cutaneous and visceral mechano-sensation and mechano-nociception (24,26,27,28); and (iv) to support acid sensing in gastroesophageal afferents (29).…”

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confidence: 99%

Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions

Delaunay

Gasull

Salinas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particularly important sensor of nonadaptive pain associated with tissue acidosis. However, little is known about the human ASIC3 channel, which includes three splice variants differing in their C-terminal domain (hASIC3a, hASIC3b, and hASIC3c). hASIC3a transcripts represent the main mRNAs expressed in both peripheral and central neuronal tissues (dorsal root ganglia [DRG], spinal cord, and brain), where a small proportion of hASIC3c transcripts is also detected. We show that hASIC3 channels (hASIC3a, hASIC3b, or hASIC3c) are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0), an original and inducible property yet unknown. When the external pH decreases, hASIC3 display a transient acid mode with brief activation that is relevant to the classical ASIC currents, as previously described. On the other hand, an external pH increase activates a sustained alkaline mode leading to a constitutive activity at resting pH. Both modes are inhibited by the APETx2 toxin, an ASIC3-type channel inhibitor. The alkaline sensitivity of hASIC3 is an intrinsic property of the channel, which is supported by the extracellular loop and involves two arginines (R68 and R83) only present in the human clone. hASIC3 is thus able to sense the extracellular pH in both directions and therefore to dynamically adapt its activity between pH 5.0 and 8.0, a property likely to participate in the fine tuning of neuronal membrane potential and to neuron sensitization in various pH environments. sodium channels | nociception A cid-sensing ion channels (ASICs) are depolarizing cationic channels gated by extracellular protons (1-3). Four genes encoding at least six subunits (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4) have been identified so far in rodents. Functional channels have been proposed to result from the trimeric association of subunits (4), leading to homomeric or heteromeric channels. ASICs are largely expressed in neurons, both in central and peripheral nervous systems. Whereas ASIC1a and ASIC2 are widely present in the rodent nervous system, the expression of ASIC1b and ASIC3 is primarily restricted to sensory neurons (5-7). The ASIC3 subunit is highly expressed in rat nociceptive neurons (8, 9). The expression pattern of ASIC subunits is less well documented in humans, where ASIC3 (10-12) has three variants differing in their C-termini (2). The physiological relevance and properties of these human variants have so far never been studied.Several physiological and/or physiopathological conditions, such as synaptic transmission, bone resorption, ischemia, inflammation, tumor development, or tissue incisions, are accompanied by extracellular acidifications. Moreover, tissue acidosis is well known to be painful (13) and inhibition of ASICs in healthy human volunteers (14, 15) has revealed the important role of these channels in sensing acid-induced pain provoked by c...

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Acid-Sensing Ion Channels in Postoperative Pain

Cited by 154 publications

References 46 publications

Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms

Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms

Preclinic and clinic effectiveness of gabapentin and pregabalin for treatment of neuropathic pain in rats and diabetic patients

Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions

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