The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in ratsThe selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats
Faculty of Medicine and Health Sciences
Translational Neurosciences (TNW)
2016London :Nature Publishing Group, 2016
Engineering sciences. Technology
Scientific reports. - London, 2011, currens
6(2016), 11 p.
University of Antwerp
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.