Sensing acidosis: nociception or sngception?

Lin, Ji-Ping; Hung, Chih-Hsien; Han, Der‐Sheng; Chen, Shih Ting; Lee, Cheng‐Han; Sun, Wei; Chen, Chih‐Cheng

doi:10.1186/s12929-018-0486-5

Cited by 29 publications

(38 citation statements)

References 58 publications

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“…These ASIC1b-expressing DRG neurons with I ASIC were medium- to large-sized neurons with diameters ranging from 30 to 55 μm. The heterogeneity of the ASIC1b-expressing DRG neurons suggest that they might play multiple roles in different physiological and pathological contexts, because ASICs are proposed as dual-function proteins for acid- and mechanosensing (Cheng et al, 2018; Chuang et al, 2018; Lin et al, 2018). Especially, the expression of ASIC1b in large-diameter DRG neurons might implicate its role in proprioception similar to ASIC3 (Lin et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Because ASICs can be activated in physiological pH ranges, ASICs seem to be the fine acid sensors involved in acidosis-induced muscle pain (Immke and McCleskey, 2001; Birdsong et al, 2010; Reimers et al, 2017). Reduced pH value in muscle tissue elicited by ischemic myalgia, inflammation, lesions, tumors or fatiguing exercise results in ASIC activation and nociceptive transduction (Cheng et al, 2018; Lin et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Acid-Sensing Ion Channel 1b in the Development of Acid-Induced Chronic Muscle Pain

et al. 2019

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Acid-sensing ion channels (ASICs) are important acid sensors involved in neural modulation in the central nervous system and pain-associated tissue acidosis in the peripheral system. Among ASIC subtypes, ASIC1b is the most selectively expressed in peripheral sensory neurons. However, the role of ASIC1b is still elusive in terms of its functions and expression profile. In this study, we probed the role of ASIC1b in acid-induced muscle pain in Asic1b-knockout (Asic1b–/–) and Asic1b-Cre transgenic (Asic1bCre) mice. We tested the effect of ASIC1b knockout in a mouse model of fibromyalgia induced by dual intramuscular acid injections. In this model, a unilateral acid injection to the gastrocnemius muscle induced transient bilateral hyperalgesia in wild-type (Asic1b+/+) but not Asic1b–/– mice; a second acid injection, spaced 1 or 5 days apart, to the same muscle induced chronic hyperalgesia lasting for 4 weeks in Asic1b+/+ mice, but the duration of hyperalgesia was significantly shortened in Asic1b–/– mice. Mambalgin-1, an ASIC1b-containing channel inhibitor that was mixed with acid saline at the first injection, dose-dependently blocked the acid-induced transient and chronic hyperalgesia in Asic1b+/+ mice. In contrast, psalmotoxin 1 (PcTx1), an ASIC1a-selective antagonist, had no effect on acid-induced transient or chronic hyperalgesia. We used whole-cell patch clamp recording to study the properties of acid-induced currents in ASIC1b-expressing dorsal root ganglia (DRG) neurons from Asic1bCre-TdTomato reporter mice. Medium- to large-sized ASIC1b-expressing DRG neurons mainly exhibited an amiloride-sensitive ASIC-like biphasic current (IASIC) in response to acid stimulation, whereas small- to medium-sized ASIC1b-expressing DRG neurons predominantly exhibited an amiloride-insensitive sustained current. Specifically, mambalgin-1 selectively inhibited the IASIC in most ASIC1b-expressing DRG neurons. However, PcTx1 or APETx2 (an ASIC3-selective antagonist) had only a mild inhibitory effect on IASIC in about half of the ASIC1b-expressing DRG neurons. In situ hybridization revealed that ASIC1b-positive DRG neurons co-expressed highly with ASIC1a and ASIC2a mRNA and partially with ASIC3 and ASIC2b. Thus, ASIC1b might form a wide variety of heteromeric channels. ASIC1b-containing heteromeric channels might be promising targets for the therapeutic treatment of acid-induced chronic muscle pain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of Acid-Sensing Ion Channel 1b in the Development of Acid-Induced Chronic Muscle Pain

et al. 2019

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“…ASIC3 is a voltage-independent sodium channel activated by the extracellular protons. It has been found as a molecular determinant involved in pain-associated tissue acidosis [58,59]. As well, a recent study showed that ASIC3 can detect extracellular acidification and also respond to mechanical stimuli [60,61].…”

Section: Sp-mediated Anti-nociception In Musclementioning

confidence: 99%

Ion Channels Involved in Substance P-Mediated Nociception and Antinociception

Chang

Jiang

Chen

2019

IJMS

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Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.

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“…This effect is associated with opioid receptors activation [26]. There are also evidences that SP influences decrease of pain sensations in muscles by alterations in ion channels activity [27]. Our findings may suggest that increase of SP concentration contributes to pain sensations decrease, however further studies are necessary to verify this effect.…”

Section: Discussionmentioning

confidence: 50%