Iloprost-induced nociception: determination of the site of anti-nociceptive action of cyclooxygenase inhibitors and the involvement of cyclooxygenase products in central mechanisms of nociception.
The writhing response to acute nociception has been used to test the analgesic activity of drugs in rodents. Dilute acetic acid is the most frequently used irritant to induce writhing behaviour. The administration of acetic acid intraperitoneally activates both peripheral and central mechanisms of nociception. It releases nociceptive mediators such as prostaglandins (PG) E(2)and I(2)at the site of noxious stimulation, the peritoneal cavity, and at central sites such as the dorsal horn of the spinal cord and some brain regions. We have used the PGI(2)mimetic, iloprost, an agonist at the IP receptor, to induce the writhing response in mice. Iloprost activates the IP receptors on peripheral nociceptors directly and thus does not release nociceptive prostaglandins into the peritoneal cavity. However, prostaglandins are still involved in nociceptive transmission at the spinal and supraspinal levels. Using this model of nociception, it is possible to identify the site of action of analgesic drugs which reduce prostaglandin release in central tissues through inhibition of cyclooxygenase. Thus, a drug that inhibits the iloprost-induced writhing response and reduces release of prostaglandins in the central nervous system is likely to be a centrally acting analgesic drug. This chapter compares the iloprost- and acetic acid-induced writhing responses in mice and describes a method for measuring central prostaglandin levels. Part of this work has been published previously.
Ayoub
Samir S
SS
Centre for Biochemical Pharmacology, Experimental Pathology Group, St. Bart's and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
Botting
Regina M
RM
D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D016285:Iloprost; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D016285:Iloprost; D015232:Dinoprostone; D019342:Acetic Acid