A comparison of the antinociceptive effects of voltage-activated Na+ channel blockers in two rat models of neuropathic pain.
The pain-relieving effects of various voltage-activated Na(+) channel blockers have been evaluated in two rat models of neuropathic pain; the photochemically induced nerve injury model (Gazelius) and spared nerve injury model. Lidocaine (up to 40 mg/kg, i.p.) and lamotrigine (up to 60 mg/kg, i.p.) had no effect on mechanical or cold allodynia in either model. However, lamotrigine (10, 30 and 60 mg/kg) significantly attenuated mechanical hyperalgesia in the spared nerve injury model, while mexiletine (25 and 37.5 mg/kg, i.p.) attenuated mechanical allodynia in the Gazelius model. Tocainide (50, 75 and 100 mg/kg, i.p.) significantly reduced all types of pain behaviour measured. The present results show that these voltage-activated Na(+) channel blockers have broadly similar antinociceptive effects in these two models of neuropathic pain. They also show that these drugs can have markedly different effects on distinct neuropathic pain-related behaviours within models.
Erichsen
Helle Kirstein
HK
Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750, Ballerup, Denmark.
Hao
Jing-Xia
JX
Xu
Xiao-Jun
XJ
Blackburn-Munro
Gordon
G
D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000187:drug effects / Q000293:injuries / Q000294:innervation; D000077213:Lamotrigine; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D009437:Neuralgia / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors; D016677:Tocainide / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
D000700:Analgesics; D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014227:Triazines; D008801:Mexiletine; D016677:Tocainide; D008012:Lidocaine; D000077213:Lamotrigine