title: Lacosamide has protective disease modifying properties in experimental vincristine neuropathy.
abstract: Pain and paresthesias are the most common symptoms of chemotherapy induced painful neuropathy (CIPN). Current treatment and preventive strategies of CIPN are ineffective, and the neuropathy may lead to discontinuation of anti-tumor therapy. Here we used experimental vincristine-induced neuropathy in rats to evaluate the disease modifying potential of lacosamide using a sustained release formulation and the acute treatment effects of a rapid release formulation. Pain behavior was assessed by withdrawal responses to von Frey hairs, acetone drops, the Randall-Selitto device, and to radiant heat. Neuropathy was assessed using electrophysiological recordings. Preventive lacosamide treatment (30 mg/kg subcutaneously b.i.d. for 17 days) was well tolerated, and pharmacokinetic analysis revealed a peak plasma concentration 2 h post-injection with a plasma half-life of approximately 3 h. Rats treated with lacosamide, in contrast to vehicle treated rats, did not develop vincristine-induced cold allodynia. Neurophysiology showed a delayed F-wave latency in vehicle treated rats, which was not present in lacosamide treated animals. We could thus demonstrate a protective disease modifying potency of lacosamide in an animal model of CIPN. Lacosamide may be a promising candidate for preventive treatment of CIPN in patients receiving chemotherapy with vinca alkaloids or platinum drugs.
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany. Geis_C@klinik.uni-wuerzburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Geis
authors.forename: Bettina K
authors.initials: BK
authors.lastname: Beyreuther
authors.forename: Thomas
authors.initials: T
authors.lastname: Stöhr
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000078334:Lacosamide; D008297:Male; D009437:Neuralgia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014750:Vincristine / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D000081:Acetamides; D018696:Neuroprotective Agents; D000078334:Lacosamide; D014750:Vincristine