Effects of ralfinamide in models of nerve injury and chemotherapy-induced neuropathic pain
| Autor: | Xiao-Nan Liang, Ruibin Su, Gang Yu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Gabapentin Cyclohexanecarboxylic Acids Organoplatinum Compounds Paclitaxel Analgesic Antineoplastic Agents Blood Pressure Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Heart Rate Peripheral Nervous System Medicine Animals Amines gamma-Aminobutyric Acid Pharmacology Analgesics business.industry Ralfinamide Chronic pain medicine.disease Low back pain Rats Fluorobenzenes Oxaliplatin Disease Models Animal 030104 developmental biology Nociception Allodynia Anesthesia Neuropathic pain Neuralgia medicine.symptom business 030217 neurology & neurosurgery Locomotion medicine.drug |
| Zdroj: | European journal of pharmacology. 823 |
| ISSN: | 1879-0712 |
| Popis: | Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II trials), but it failed to ameliorate neuropathic low back pain in Phase III trials. It is unclear whether ralfinamide is effective against neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of ralfinamide in neuropathic pain models induced by spared nerve injury and chemotherapy were compared in a gabapentin-controlled manner. The effects of ralfinamide on physiological pain were evaluated in mechanical withdrawal, hot plate, and acetic acid writhing tests. We also investigated the effects of ralfinamide on cardiovascular function and locomotor activity. Oral ralfinamide dose-dependently alleviated spared nerve injury-induced allodynia in rats and mice. Ralfinamide increased mechanical withdrawal thresholds in oxaliplatin-induced and paclitaxel-induced neuropathic pain. Ralfinamide did not affect physiological pain, locomotion, or cardiovascular function. Together, ralfinamide attenuated mechanical allodynia in all the neuropathic pain models tested, with subtle differences in efficacy. The effect of ralfinamide is comparable to that of gabapentin, but with no interference in basal mechanical sensitivity. The present study supports the effectiveness of selective sodium channel blockade as an analgesic strategy, as well as the development of compounds similar to ralfinamide. |
| Databáze: | OpenAIRE |
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