The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain.
The novel anti-epileptic drugs lamotrigine, felbamate and gabapentin were compared in rat experimental models of acute (tail flick) and chronic pain: the chronic constriction injury and spinal nerve ligation models. Lamotrigine (10-100 mg/kg, s.c.), felbamate (150-600 mg/kg, i.p.) and gabapentin (30-300 mg/kg, i.p.) each reversed cold allodynia (chronic constriction injury model) with ED50 values of 28, 241 and 103 mg/kg, respectively, 1 h post-dose. However, only gabapentin reversed tactile allodynia (spinal nerve ligation model) with an ED50 of 34 mg/kg (i.p.). The established anti-epileptic drugs, carbamazepine (1-30 mg/kg, i.p.) and phenytoin (1-100 mg/kg, s.c.), were ineffective in both models. The anti-allodynic effect of the newer anti-epileptic drugs was observed at doses that were either ineffective or produced only a negligible effect on acute nociceptive function and/or locomotor activity. In conclusion, the data suggest that the newer anti-epileptic drugs appear to have the potential to be effective alternatives to either carbamazepine or phenytoin in the treatment of neuropathic pain. However, only gabapentin ameliorated both cold and touch hyperesthesias.
Hunter
J C
JC
Department of Analgesia, Institute of Pharmacology, Roche Bioscience, Palo Alto, CA 94304, USA. john.hunter@roche.com
Gogas
K R
KR
Hedley
L R
LR
Jacobson
L O
LO
Kassotakis
L
L
Thompson
J
J
Fontana
D J
DJ
D000085:Acetates / Q000627:therapeutic use*; D000208:Acute Disease; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D002908:Chronic Disease; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004597:Electroshock / Q000379:methods; D000078328:Felbamate; D000077206:Gabapentin; D000077213:Lamotrigine; D008297:Male; D010146:Pain / Q000188:drug therapy*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077213:Lamotrigine; D000078328:Felbamate