Prostaglandins, glutamate and nitric oxide synthase mediate nitroglycerin-induced hyperalgesia in the formalin test.
Increasing evidence supports a possible role for nitric oxide (NO) in the transmission of pain signals and in the development of central mechanisms of hyperalgesia. Previously, we have shown that nitroglycerin, an NO donor, is able to induce a long-lasting hyperalgesic state in rats. Nitroglycerin-induced hyperalgesia can be detected as an increase in the nociceptive behavior evoked by the formalin test. In the present study we investigated the possible mediators in the nitroglycerin-induced hyperalgesic state. Male Sprague-Dawley rats were injected with nitroglycerin and pretreated with indomethacin, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) or N(omega)-nitro-L-arginine methyl ester (L-NAME). The results obtained showed that inhibition of prostaglandins or NO synthesis prevents nitroglycerin-induced hyperalgesia in Phase II of the formalin test. A similar inhibitory effect was also observed following pretreatment with the glutamate antagonist MK801. The present findings point to the role of prostaglandins, NO synthesis and glutamate activity in the induction of nitroglycerin-induced hyperalgesia.
Tassorelli
Cristina
C
Laboratory of Pathophysiology of Integrative Autonomic Systems, University Center for the Study of Adaptive Disorders and Headache, IRCCS C. Mondino Institute of Neurology Foundation, Pavia, Italy.
Greco
Rosaria
R
Wang
Dechun
D
Sandrini
Giorgio
G
Nappi
Giuseppe
G
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005557:Formaldehyde; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D005996:Nitroglycerin; D010146:Pain / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011453:Prostaglandins; D005557:Formaldehyde; D009569:Nitric Oxide; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin