The intrathecal administration of excitatory amino acid receptor antagonists selectively attenuated carrageenan-induced behavioral hyperalgesia in rats

Eur J Pharmacol. 1992 Aug 25;219(2):235-43. doi: 10.1016/0014-2999(92)90301-j.


A single unilateral injection of carrageenan (4.5-6.0 mg in 0.15-0.20 ml saline) into the rat hindpaw induced behavioral hyperalgesia as evidenced by a significant reduction in hindpaw withdrawal latency to a noxious thermal stimulus. The involvement of N-methyl-D-aspartate (NMDA) receptors in this model of hyperalgesia was examined by intrathecal administration of the selective excitatory amino acid (EAA) receptor antagonists: (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), ketamine hydrochloride (ketamine), 7-chlorokynurenic acid (7-Cl kynurenic acid), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The effects of dizocilpine maleate (MK-801) were studied under the same conditions and published previously (Ren et al., 1992) and the data are presented for comparison. While the withdrawal latencies of the non-injected paws and of the paws of naive rats were not significantly affected by application of the EAA receptor antagonists at doses tested, the paw withdrawal latencies of the carrageenan-injected paws were elevated dose dependently. The rank order of potency of these agents to reduce hyperalgesia was: MK-801 greater than or equal to AP-5 greater than or equal to CPP = 7-Cl kynurenic acid = ketamine much greater than CNQX greater than 0. In contrast, intrathecal injection of the opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO, mu-selective) and [D-Pen2,D-Pen5] enkephalin (DPDPE, delta-selective), produced antinociception in both injected and non-injected paws. DAMGO was much more potent, while DPDPE was less potent, than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Analgesics / pharmacology
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Carrageenan / toxicity
  • Dizocilpine Maleate / pharmacology
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / pharmacology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Inflammation / physiopathology
  • Injections, Spinal
  • Ketamine / pharmacology
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • Male
  • Piperazines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Valine / analogs & derivatives
  • Valine / pharmacology


  • Analgesics
  • Enkephalins
  • Piperazines
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Ketamine
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Enkephalin, D-Penicillamine (2,5)-
  • Carrageenan
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Kynurenic Acid
  • Valine
  • 7-chlorokynurenic acid