Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine.
BACKGROUND
We tested the hypothesis that acetyl-L-carnitine (ALC) may have a protective and a curative role in chemotherapy-induced hyperalgesia in vivo, in animal models of cisplatin-, paclitaxel- and vincristine-induced neuropathy. In addition, the possible interaction between ALC and vincristine antineoplastic action was assessed.


METHODS
Chemotherapy-induced peripheral neuropathy (CIPN) was induced in different groups of rats. The effect of ALC was evaluated both when its administration was started together with the administration of anticancer drugs ("preventive" protocol) and when ALC administration was started later on during treatment ("curative" protocol).


RESULTS
The ALC treatment significantly prevented the lowering of the mechanical nociceptive threshold when the administration started concomitantly and, respectively, with cisplatin, paclitaxel and vincristine as compared to each drug alone. Furthermore, when ALC administration was started later on during treatment, at well-established neuropathy, ALC was able to restore the mechanical nociceptive threshold within a few days. Finally, experiments indicated that ALC does not interfere with the antitumor effects of vincristine.


CONCLUSIONS
Considering the absence of any satisfactory treatment currently available for CIPN in a clinical setting, these are important observations, opening up the possibility of using ALC to treat a wide range of patients who have undergone chemotherapy and developed sensory peripheral neuropathy.
Ghirardi
Orlando
O
Research and Development, Sigma-Tau S.p.A. Industrie Farmaceutiche Riunite, Rome, Italy. orlando.ghirardi@sigma.tau.it
Vertechy
Mario
M
Vesci
Loredana
L
Canta
Annalisa
A
Nicolini
Gabriella
G
Galbiati
Stefania
S
Ciogli
Cristina
C
Quattrini
Gianni
G
Pisano
Claudio
C
Cundari
Sante
S
Rigamonti
Laura Maria
LM
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity; D004195:Disease Models, Animal; D017239:Paclitaxel / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D014750:Vincristine / Q000633:toxicity
D000970:Antineoplastic Agents; D014750:Vincristine; D000108:Acetylcarnitine; D017239:Paclitaxel; D002945:Cisplatin