The long-term effect of epidural administration of butamben suspension on nerve injury-induced allodynia in rats.
Although local anesthetics can, in some situations, alleviate neuropathic pain, currently available preparations are short-acting and nonselective, producing, for example, motor dysfunction. Clinical studies report that a novel suspension preparation of butamben has the advantage of a prolonged duration of action, and it can be used epidurally, without impairment of motor function. In this behavioral study, we investigated the effect of the epidural administration of a 5% butamben suspension on nerve injury-induced allodynia. Behavioral studies were performed using an established animal model of neuropathic pain, which involves a partial ligation of the sciatic nerve. Nociceptive thresholds to mechanical stimulation were determined by the paw withdrawal method. The allodynia to mechanical stimulation induced by partial nerve ligation was significantly attenuated by daily injections, for 5 days, of 10 microL of butamben suspension. The analgesia lasted at least 7 days after the final injection. Daily injections of 10 microL of vehicle, for 5 days, had no significant effect on allodynia. During the period of daily injections, both the butamben and vehicle treated rats had temporary impairment of motor coordination compared with untreated controls. Motor function recovered after the final injection. Neither daily injections of butamben for 2 or 3 days, nor smaller volumes for 5 days (2.5-5 microL), had a long-lasting effect. We conclude that repeated epidural administration of butamben suspension for several days provides long-lasting analgesia in rats with nerve injury-induced allodynia to mechanical stimulation.


CONCLUSIONS
In this animal behavioral study, using rats with nerve injury-induced pain, we examined the possible long-term analgesic effects of epidural administration of a suspension of the local anesthetic, butamben. We found that multiple doses for several days were required to provide a prolonged analgesia.
Mitchell
V A
VA
Department of Anaesthesia and Pain Management, University of Sydney, Royal North Shore Hospital, St. Leonards, Australia.
White
D M
DM
Cousins
M J
MJ
D015360:Analgesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001566:Benzocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D008124:Locomotion / Q000187:drug effects; D008137:Longitudinal Studies; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D009619:Nociceptors / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D014677:Pharmaceutical Vehicles; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries*; D013997:Time Factors
D000779:Anesthetics, Local; D014677:Pharmaceutical Vehicles; C004605:butamben; D001566:Benzocaine