The role of nitric oxide and prostaglandin E2 on the hyperalgesia induced by excitatory amino acids in rats.
The present study was designed to investigate the role of nitric oxide (NO), N-methyl-D-aspartate (NMDA) receptor and prostaglandins on hyperalgesia induced in rats by excitatory amino acids and the possibility that prostaglandins may act as the retrograde messenger in the spinal cord like NO. Nomega-nitro-L-arginine methyl ester (L-NAME; 500 microg/paw, intraplantarly (i.pl.)), MK-801 (10 microg/paw, i.pl.) or indomethacin (300 microg/paw, i.pl.) reduced the duration of phase 2 of the biting/licking and scratching (B/L + S) response induced by formalin injection from 255.6+/-16.7 s to 155.6+/-16.9, 172.25+/-33.3 or 205.6+/-16.7 s, respectively. L-NAME (0.3 mg, i.th.), MK-801 (8 microg, i.th.) or indomethacin (20 microg, i.th) reduced the duration of phase 2 of the B/L + S response induced by saline injection from 288.5+/-7.7s to 207.7+/-19.2, 184.6+/-7.7 or 1923+/-38.5 s, respectively. L-NAME or indomethacin injected into the spinal cord of the rat significantly reduced the hyperalgesia induced by NMDA (1 microg, i.th.) from 43.8+/-4.6% to 12.3+/-3.1 and 19.2+/-2.3%, respectively. It is assumed that NO produced by excitatory amino acids may increase prostaglandin production by cyclooxygenase activation. L-NAME, MK-801 or indomethacin injected into the rat spinal cord significantly reduced the hyperalgesia induced by prostaglandin E2 (PGE2, 25 ng, i.th.) in the tail-flick test from 40.6+/-3.5% to 18.2+/-3.2, 18.8+/-1.8 or 17.6+/-4.1%, respectively, but had little effect on hyperalgesia in the paw pressure test (except for indomethacin). In conclusion, NO and PGE2 affect the hyperalgesia induced by excitatory amino acids. It is suggested that PGE2, like NO, may act as a retrograde messenger in the spinal cord.
Park
Y H
YH
Department of Pharmacology, School of Pharmacy, Chung Ang University, Seoul, Republic of Korea.
Shin
C Y
CY
Lee
T S
TS
Huh
I H
IH
Sohn
U D
UD
D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000008:administration & dosage*; D005557:Formaldehyde / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018846:Excitatory Amino Acids; D005557:Formaldehyde; D009569:Nitric Oxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin