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Title
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The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats
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Author
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Abstract
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| E-52862 is a selective sigma R-1 antagonist currently undergoing phase II clinical trials for neuropathic pain and represents a potential first-in-class analgesic. Here, we investigated the effect of single and repeated administration of E-52862 on different pain-related behaviours in several neuropathic pain models in rats: mechanical allodynia in cephalic (trigeminal) neuropathic pain following chronic constriction injury of the infraorbital nerve (IoN), mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic polyneuropathy, and cold allodynia in oxaliplatin (OX)-induced polyneuropathy. Mechanical hypersensitivity induced after IoN surgery or STZ administration was reduced by acute treatment with E-52862 and morphine, but not by pregabalin. In the OX model, single administration of E-52862 reversed the hypersensitivity to cold stimuli similarly to 100 mg/kg of gabapentin. Interestingly, repeated E-52862 administration twice daily over 7 days did not induce pharmacodynamic tolerance but an increased antinociceptive effect in all three models. Additionally, as shown in the STZ and OX models, repeated daily treatment with E-52862 attenuated baseline pain behaviours, which supports a sustained modifying effect on underlying pain-generating mechanisms. These preclinical findings support a role for sigma R-1 in neuropathic pain and extend the potential for the use of selective sigma R-1 antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain. |
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Language
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English
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Source (journal)
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Scientific reports. - London, 2011, currens
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Publication
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London
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Nature Publishing Group
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2016
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ISSN
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2045-2322
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DOI
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10.1038/SREP24591
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Volume/pages
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6
(2016)
, 11 p.
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Article Reference
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24591
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ISI
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000374253000002
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Pubmed ID
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27087602
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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