Title
The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London :Nature Publishing Group ,
Subject
Engineering sciences. Technology
Source (journal)
Scientific reports. - London, 2011, currens
Volume/pages
6(2016) , 11 p.
ISSN
2045-2322
2045-2322
Article Reference
24591
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/177923/133595.pdf
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