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The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats
- Source :
- Scientific reports, Scientific Reports
- Publication Year :
- 2016
-
Abstract
- E-52862 is a selective σ1R 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 σ1R in neuropathic pain and extend the potential for the use of selective σ1R antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain.
- Subjects :
- Male
0301 basic medicine
Organoplatinum Compounds
Gabapentin
Morpholines
Analgesic
Pregabalin
Pharmacology
Article
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Diabetic Neuropathies
Peripheral Nerve Injuries
Animals
Receptors, sigma
Medicine
Analgesics
Multidisciplinary
business.industry
medicine.disease
Rats
Oxaliplatin
030104 developmental biology
Allodynia
Nociception
Hyperalgesia
Anesthesia
Neuropathic pain
Neuralgia
Pyrazoles
medicine.symptom
business
Polyneuropathy
Engineering sciences. Technology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....5416073c74aeae0db6fd6c7ceb3cc592