Analgesic effects of gabapentin on mechanical hypersensitivity in a rat model of chronic pancreatitis.
Gabapentin, an anticonvulsant, is widely accepted as an alternative therapeutic agent for neuropathic pain and has proved to produce analgesic effects in a mouse model of visceral pain. However, it is unknown whether gabapentin is also analgesically effective in chronic pancreatitis. The aim of the present study was to investigate the role and underlying mechanisms of gabapentin in a rat model of chronic pancreatitis. Chronic pancreatitis induced by dibutyltin dichloride (DBTC) produced a marked increase in mechanical sensitivity of the abdomen after the establishment of the model. During the first day to the sixth day in the fourth week, Gabapentin was administered intraperitoneally daily at a dose of 100mg/kg. The behavioral test began 1h after drug administration. The analgesic effect of gabapentin was not evident with a single injection, but gabapentin significantly reduced the responsive frequencies to mechanical stimulation in rats with chronic pancreatitis from the third day to the end of the experiment. To explore the underlying mechanisms, the expression of alpha(2)delta-1 calcium channel subunit was examined in the thoracic spinal cord (T8-11). There was no significant change in alpha(2)delta-1 level of T8-11 following the first injection. But after the sixth injection, the alpha(2)delta-1 level of T8-11 in rats with chronic pancreatitis was declined. Taken together, the present study suggested that repeated administration of gabapentin daily could reduce mechanical hypersensitivity in the upper abdomen and produce an analgesic effect in a rat model of chronic pancreatitis. The down-regulation of alpha(2)delta-1 calcium channel subunit might be one of the mechanisms underlying the analgesic effect of gabapentin.
Liao
Xing-zhi
XZ
Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Zhou
Mai-Tao
MT
Mao
Yan-Fei
YF
Xu
Hua
H
Chen
Hui
H
Sun
Ji-Hu
JH
Xiong
Yuan-Chang
YC
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D020746:Calcium Channels, L-Type; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077206:Gabapentin; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D009947:Organotin Compounds / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D011920:Rats, Inbred WF; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; C486060:Cacna2d1 protein, rat; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D003509:Cyclohexanecarboxylic Acids; D007166:Immunosuppressive Agents; D009947:Organotin Compounds; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C020735:dibutyldichlorotin