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

Deval, Emmanuel; Gasull, Xavier; Noël, Jacques; Salinas, Miguel; Baron, Anne; Diochot, Sylvie; Lingueglia, Éric

doi:10.1016/j.pharmthera.2010.08.006

Cited by 285 publications

(230 citation statements)

References 163 publications

Supporting

Mentioning

224

Contrasting

Unclassified

Order By: Relevance

“…112 Alternative drugs or ASIC blockers are amiloride, A-317567, metallic ions (Gd 3+ , Pb 2+ , Ni 2+ , Cd 2+ and Cu 2+ ) and divalent cations (Ca 2+ , Mg 2+ and Zn 2+ ). 113 In peripheral inflammation models, the administration of amiloride and benzamil also inhibits ASIC channels and produces, thus, a decrease in pain responses. 114 A second therapeutic strategy against neuropathic pain lies in reducing hyperexcitability of the injured nociceptive somatosensory system by 'modulation of voltage-dependent and/or ligand-gated ion channels'.…”

Section: Therapeutic Approaches In Neuropathic Pain Based On the Neurmentioning

confidence: 99%

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

et al. 2016

View full text Add to dashboard Cite

Study design: This is a narrative review of the literature. Objectives: This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. Setting: This study was conducted in Girona, Catalonia, Spain. Methods: A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. Results and conclusion: Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltagegated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness than classical drug treatments. Although research efforts have already focused on these aspects, additional research may be necessary to further explore the potential therapeutic targets in neuropathic pain involved in the neuroplasticity changes of neuropathological pathways from the injured somatosensory system.

show abstract

Section: Therapeutic Approaches In Neuropathic Pain Based On the Neurmentioning

confidence: 99%

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For example, intracranial self-stimulation (ICSS) is an operant procedure in which subjects emit a learned response such as a lever press to earn pulses of electrical stimulation to brain reward areas (Carlezon and Chartoff, 2007;Olds and Milner, 1954). Tissue acidosis is a cardinal component of inflammation that contributes to nociception and pain (Bray et al, 2013;Deval et al, 2013), and intraperitoneal (i.p.) administration of exogenous acid functions as one type of physiologically relevant noxious visceral stimulus that depresses ICSS (Pereira Do Carmo et al, 2009;Negus, 2013).…”

Section: Introductionmentioning

confidence: 99%

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

Leitl

Onvani

Bowers

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This study tested the hypothesis that pain-related behavioral depression is mediated by activation of endogenous k-opioid systems and subsequent depression of mesolimbic dopamine release. Adult male Sprague-Dawley rats were implanted with electrodes targeting the medial forebrain bundle (for behavior studies of intracranial self-stimulation (ICSS)) or with cannulae for microdialysis measures of nucleus accumbens dopamine (NAc DA). Changes in ICSS and NAc DA were examined after treatment with a visceral noxious stimulus (intraperitoneal injection of dilute lactic acid) or an exogenous k-agonist (U69593). Additional studies examined the sensitivity of acid and U69593 effects to blockade by two analgesics (the nonsteroidal antiinflammatory drug ketoprofen and the m-opioid agonist morphine) or by the k-antagonist norbinaltorphimine (norBNI). The effects of acid were also examined on mRNA expression for prodynorphin (PDYN) and k-opioid receptors (KORs) in mesocorticolimbic brain regions. Both acid and U69593 depressed ICSS and extracellular levels of NAc DA. Pain-related acid effects were blocked by ketoprofen and morphine but not by norBNI. The U69593 effects were blocked by norBNI but not by ketoprofen, and were only attenuated by morphine. Acid did not significantly alter PDYN or KOR in NAc, but it produced a delayed increase in PDYN in prefrontal cortex. These results support a key role for the mesolimbic DA system, but a more nuanced role for endogenous k-opioid systems, in mediating acute pain-related behavioral depression in rats.

show abstract

“…ASICs are Na + -permeable and, to a lesser extent, Ca 2+ -permeable channels that are activated by extracellular acidosis (13)(14)(15)(16)(17)(18)(19). In the brain, ASICs consist of homotrimeric and heterotrimeric complexes of ASIC1a, ASIC2a, and ASIC2b.…”

mentioning

confidence: 99%

Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala

Reznikov²,

Price³

et al. 2014

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

229

339

View full text Add to dashboard Cite

Stimulating presynaptic terminals can increase the proton concentration in synapses. Potential receptors for protons are acidsensing ion channels (ASICs), Na + -and Ca 2+ -permeable channels that are activated by extracellular acidosis. Those observations suggest that protons might be a neurotransmitter. We found that presynaptic stimulation transiently reduced extracellular pH in the amygdala. The protons activated ASICs in lateral amygdala pyramidal neurons, generating excitatory postsynaptic currents. Moreover, both protons and ASICs were required for synaptic plasticity in lateral amygdala neurons. The results identify protons as a neurotransmitter, and they establish ASICs as the postsynaptic receptor. They also indicate that protons and ASICs are a neurotransmitter/ receptor pair critical for amygdala-dependent learning and memory.long-term potentiation | PcTX1 | acid sensing ion channel

show abstract

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

Cited by 285 publications

References 163 publications

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala

Contact Info

Product

Resources

About