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

Abstract

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)

• Authors: K Ren, G M Williams, J L Hylden, M A Ruda, R Dubner
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 219 Issue 2 Pg. 235-43 (Aug 25 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1358641 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 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

Topics

• 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, drug therapy)
• Inflammation (physiopathology)
• Injections, Spinal
• Ketamine (pharmacology)
• Kynurenic Acid (analogs & derivatives, pharmacology)
• Male
• Piperazines (pharmacology)
• Quinoxalines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, physiology)
• Valine (analogs & derivatives, pharmacology)