Inhibition of the potassium channel K Ca 3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury.

Autor: Staal RGW; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA. Electronic address: staalro@yahoo.com., Khayrullina T; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Zhang H; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Davis S; Psychogenics Inc., 765 Old Saw Mill River Rd #104, Tarrytown, NY 10591, USA., Fallon SM; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Cajina M; Molecular Pharmacology, Bioanalysis & Operations, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA., Nattini ME; Molecular Pharmacology, Bioanalysis & Operations, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA., Hu A; Psychogenics Inc., 765 Old Saw Mill River Rd #104, Tarrytown, NY 10591, USA., Zhou H; Molecular Pharmacology, Bioanalysis & Operations, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA., Poda SB; Molecular Pharmacology, Bioanalysis & Operations, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA., Zorn S; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Chandrasena G; Molecular Pharmacology, Bioanalysis & Operations, Lundbeck Research USA Inc., 215 College Road, Paramus, NJ 07652, USA., Dale E; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Cambpell B; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA., Biilmann Rønn LC; Neurodegeneration Disease Biology Unit, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark., Munro G; Neurodegeneration Disease Biology Unit, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark., Mӧller T; Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ 07652, USA.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2017 Jan 15; Vol. 795, pp. 1-7. Date of Electronic Publication: 2016 Nov 19.
DOI: 10.1016/j.ejphar.2016.11.031
Abstrakt: Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca 2+ - activated K + channel, K Ca 3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of K Ca 3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent K Ca 3.1 inhibitor. In primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL-1β release. In vivo, senicapoc showed high CNS penetrance and when administered to rats with peripheral nerve injury, it significantly reversed tactile allodynia similar to the standard of care, gabapentin. In contrast to gabapentin, senicapoc achieved efficacy without any overt impact on locomotor activity. Together, the data demonstrate that the K Ca 3.1 inhibitor senicapoc is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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