Neuropharmacology, April, 2014, Vol.79, p.432(12)
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.neuropharm.2013.12.011 Byline: Benoit Michot, Valerie Kayser, Gerard Bastian, Sylvie Bourgoin, Michel Hamon Abstract: Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves responds differently to alleviating drugs at cephalic versus extracephalic level. Because neuropathic pain evoked by anti-cancer drugs differs from that triggered by mechanical nerve lesion, we investigated whether differences between cephalic and extracephalic levels could also be characterized in rodents rendered neuropathic by treatment with the anti-cancer platinum derivative oxaliplatin. C57BL/6J mice received two injections and Sprague-Dawley rats three injections of oxaliplatin (10 mg/kg, i.p.) or its vehicle, with three days intervals. Supersensitivity to mechanical (von Frey filaments), cold (acetone drop) and chemical/inflammatory (formalin) stimulations was assessed in vibrissae and hindpaw territories. Transcripts of neuroinflammatory markers were quantified by real-time RT-qPCR in rat ganglia and central tissues. Oxaliplatin induced mechanical allodynia, cold hyperalgesia and chemical/inflammatory supersensitivity at both hindpaw and vibrissal levels in mice and rats. Acute treatment with gabapentin (30 mg/kg i.p.), morphine (3 mg/kg s.c.) or the 5-HT.sub.1A receptor agonist 8-OH-DPAT (0.16 mg/kg s.c.) significantly reduced oxaliplatin-induced supersensitivity in hindpaw but not vibrissal territory. In contrast, the antimigraine drugs naratriptan (0.1 mg/kg s.c.) and olcegepant (0.6 mg/kg i.v.) decreased oxaliplatin-induced supersensitivity in vibrissal territory only. Among the various markers investigated, only TRPA1 transcript was upregulated in ganglia of oxaliplatin-treated rats. These data showed that oxaliplatin induced supersensitivity to various stimuli in both cephalic and extra-cephalic territories in rodents. Regional differences in the efficacy of drugs to alleviate oxaliplatin-induced allodynia/hyperalgesia further support the idea that mechanisms underlying neuropathic pain have peculiarities at cephalic versus extra-cephalic level. Author Affiliation: (a) INSERM U894 - CPN, Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, UMR S677, 91, Boulevard de l'Hopital, Paris F-75013, France (b) Departement de Pharmacologie, Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, 91, Boulevard de l'Hopital, Paris F-75013, France Article History: Received 7 August 2013; Revised 6 December 2013; Accepted 9 December 2013
Rodents ; Gabapentin ; Antineoplastic Agents ; Formaldehyde
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