Implications fonctionnelles du noyau subthalamique chez l'animal sain et dans un modèle animal analogue expérimental de la maladie de Parkinson chez le rat (Approche électrophysiologique, pharmacologique et stimulation cérébrale profonde chez le rat intact et rendu parkinsonien. Approche électrophysiologique chez le primate sain)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats

E-52862 is a selective σ(1)R 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 σ(1)R in neuropathic pain and extend the potential for the use of selective σ(1)R antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain