title: Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.
abstract: We compared the preclinical analgesic activity of three marketed drugs with different pharmacological properties, pregabalin, tramadol and duloxetine, described as effective against neuropathic pain in the clinic. These drugs were tested against evoked pain in two different neuropathic models in the rat, the Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. Although all three drugs displayed analgesic activity, the effects observed varied according to the behavioral evaluation. Pregabalin showed clear analgesic effects against cold allodynia and tactile hyperalgesia in both the CCI and Chung models. Tramadol was active against all four endpoints in the Chung model with similar effects in the CCI model, apart from tactile allodynia. Duloxetine inhibited tactile allodynia and heat hyperalgesia in both neuropathic pain models. It also displayed efficacy against tactile hyperalgesia in the CCI model and against cold allodynia in the Chung model. These data confirm that the CCI and the Chung models of neuropathic pain do not detect the activity of analgesics with the same sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the type of endpoint (allodynia or hyperalgesia) can further influence the observed efficacy of gold standards as well as novel compounds developed for treating neuropathic pain symptoms.
authors.affiliation: Porsolt S.A.S., Z.A. de Glatigné, 53940 Le Genest Saint Isle, France. Electronic address: clecudennec@porsolt.com.
authors.forename: Camille
authors.initials: C
authors.lastname: Le Cudennec
authors.affiliation: Porsolt S.A.S., Z.A. de Glatigné, 53940 Le Genest Saint Isle, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castagné
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D010812:Physical Stimulation; D000069583:Pregabalin; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000601:surgery; D013876:Thiophenes / Q000627:therapeutic use*; D014147:Tramadol / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D013876:Thiophenes; D014147:Tramadol; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000068736:Duloxetine Hydrochloride
keywords: Analgesics; Anticonvulsants; Antidepressants; Neuropathic pain; Rodents