Nicotine-induced analgesia in rats: the role of calcium and the diversity of responders and nonresponders.
Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant antinociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 microM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotine alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl2 (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.)--induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl2 completely abolishes, nicotine-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect.
Block
R C
RC
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714.
Chin
C W
CW
Wu
W
W
Zbuzek
V K
VK
D000698:Analgesia; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D004347:Drug Interactions; D004492:Edetic Acid / Q000494:pharmacology; D008297:Male; D009538:Nicotine; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D009538:Nicotine; D004492:Edetic Acid; D002122:Calcium Chloride; D002118:Calcium