Prolonged analgesic effect of amitriptyline base on thermal hyperalgesia in an animal model of neuropathic pain.
The best analgesic drugs for neuropathic pain have a long duration of action, can be given via multiple routes, and can be used preemptively. We evaluated the antinociceptive effects and duration of action of subcutaneously injected amitriptyline base (AMT-Base) (in oil). A plantar test in a spinal nerve ligation (SNL) model of neuropathic pain in rats showed that typical amitriptyline HCl (AMT-HCl) (in saline) and AMT-Base had a significant dose-dependent antinociceptive effect: the antinociceptive duration of a single 100 μmol/kg injection of AMT-HCl was 5 h and of AMT-Base was 24 h when given 7 days after a SNL, and of a single 200 μmol/kg injection of AMT-Base was 39 days when given 1 h before and 4 days when given 7 days after a SNL. The post-ligation antinociceptive duration of AMT-Base was 4.8 times that of AMT-HCl, but the duration of preemptive (pre-ligation) AMT-Base treatment was 9.7 times that of AMT-Base. We can conclude that preemptive amitriptyline base provides long-lasting antinociception for neuropathic pain experimentally.
Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
Kuo-Lun
KL
Huang
Ja-Ping
JP
Shieh
Chin-Chen
CC
Chu
Kuang-I
KI
Cheng
Jhi-Joung
JJ
Wang
Mao-Tsun
MT
Lin
Mou-Yung
MY
Yeh
D000639:Amitriptyline / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000601:surgery
D000700:Analgesics; D000639:Amitriptyline