Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway.
OBJECTIVE
Lithium, a widely used drug in bipolar-affective disorders, plays gastro-protective roles. The effects of lithium on several tissues are mediated through nitric oxide (NO), which regulates gastrointestinal motility and mucosal integrity. The aim of this study was to investigate the protective effect of chronic lithium administration on visceral hypersensitivity and to investigate the role of NO as a potential mechanism of lithium in a rat model of irritable bowel syndrome.


METHODS
Colitis was induced by the intracolonic administration of acetic acid. After subsidence of inflammation on the seventh experimental day, nociception and defecation parameters were measured. A subgroup of animals had been pretreated with lithium carbonate (600 mg/L) for 35 days. Thereafter, either a non-selective NO synthase (NOS) inhibitor (N-nitro-L-arginine methyl ester [L-NAME], 10 mg/kg), a selective NOS inhibitor (aminoguanidine, 100 mg/kg), or saline were administered intraperitoneally 1 h before measurements.


RESULTS
Chronic lithium attenuated the visceral hypersensitivity, increased the nociceptive threshold, and decreased stool frequency. L-NAME and aminoguanidine decreased the nociceptive threshold and reduced the protective effects of lithium on visceral hypersensitivity. Stool frequency was increased in both the lithium-treated and water-treated groups by L-NAME administration, but not aminoguanidine. The form of defecation in the lithium-treated rats shifted toward hard stools rather than being soft and formless, but NOS inhibitors did not change the stool consistency pattern.


CONCLUSIONS
The results indicate the antinociceptive property of chronic lithium on visceral hypersensitivity. As this effect was lowered by NOS inhibitors, NO might play a role in the protective effect of lithium to some extent.
Shamshiri
Hosein
H
Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran, Iran.
Paragomi
Pedram
P
Paydar
Mehrak Javadi
MJ
Moezi
Leila
L
Bahadori
Moslem
M
Behfar
Behnaz
B
Ardalan
Farid A
FA
Dehpour
Ahmad R
AR
D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D003967:Diarrhea / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006146:Guanidines / Q000008:administration & dosage; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016651:Lithium Carbonate / Q000008:administration & dosage*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000294:innervation; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology
D000700:Analgesics; D004791:Enzyme Inhibitors; D006146:Guanidines; D016651:Lithium Carbonate; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester