Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain

Autor: Alain Eschalier, Sylvie Diochot, Abdelkrim Alloui, Mélodie Dauvois, Youssef Aissouni, Anne Baron, Eric Lingueglia, Valérie Friend, Précillia Rodrigues
Přispěvatelé: Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Pharmacologie fondamentale et clinique de la douleur, Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), BARON, Anne, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Analgesic
Inflammation
Pharmacology
03 medical and health sciences
Route of administration
Mice
Xenopus laevis
0302 clinical medicine
medicine
Animals
Ion channel
Acid-sensing ion channel
Elapid Venoms
Mice
Knockout
Analgesics
business.industry
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
medicine.disease
3. Good health
Mambalgins
Rats
Mice
Inbred C57BL
030104 developmental biology
Anesthesiology and Pain Medicine
Treatment Outcome
Neurology
Acid Sensing Ion Channel Blockers
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Neuropathic pain
Neuralgia
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Female
Neurology (clinical)
medicine.symptom
business
Peptides
030217 neurology & neurosurgery
Zdroj: PAIN
PAIN, Elsevier, 2016, 157 (3), pp.552-559. ⟨10.1097/j.pain.0000000000000397⟩
PAIN, 2016, 157 (3), pp.552-559. ⟨10.1097/j.pain.0000000000000397⟩
Pain
Pain, 2016, 157 (3), pp.552-559. ⟨10.1097/j.pain.0000000000000397⟩
ISSN: 0304-3959
1872-6623
DOI: 10.1097/j.pain.0000000000000397⟩
Popis: International audience; Mambalgins are 57-amino acid peptides isolated from snake venom that evoke naloxone-resistant analgesia after local (intraplantar) and central (intrathecal) injections through inhibition of particular subtypes of acid-sensing ion channels (ASICs). We now show that mambalgins also have an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic intravenous (i.v.) administration and are effective against neuropathic pain. By combining the use of knockdown and knockout animals, we show the critical involvement of peripheral ASIC1b-containing channels, along with a contribution of ASIC1a-containing channels, in the i.v. effects of these peptides against inflammatory pain. The potent analgesic effect on neuropathic pain involves 2 different mechanisms depending on the route of administration, a naloxone-insensitive and ASIC1a-independent effect associated with i.v. injection and an ASIC1a-dependent and partially naloxone-sensitive effect associated with intrathecal injection. These data further support the role of peripheral and central ASIC1-containing channels in pain, demonstrate their participation in neuropathic pain, and highlight differences in the repertoire of channels involved in different pain conditions. They also strengthen the therapeutic potential of mambalgin peptides that are active in a broader range of experimental pain models and through i.v. systemic delivery.
Databáze: OpenAIRE
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