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

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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 ≥ AP-5 ≥ CPP = 7-Cl kynurenic acid = ketamine ⪢ CNQX > 0. In contrast, intrathecal injection of the opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO, μ-selective) and [D-Pen2,D-Pen5] enkephalin (DPDPE, δ-selective), produced antinociception in both injected and non-injected paws. DAMGO was much more potent, while DPDPE was less potent, than MK-801. It is concluded that NMDA receptors are involved in the development of carrageenan-induced thermal hyperalgesia.

References (43)

  • K. Hargreaves et al.

    A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia

    Pain

    (1988)
  • J.L.K. Hylden et al.

    Expansion of receptive fields of spinal lamina I projection neurons in rats with unilateral adjuvant-induced inflammation: the contribution of dorsal horn mechanisms

    Pain

    (1989)
  • J.L.K. Hylden et al.

    Spinal opioid analgesic effects are enhanced in a model of unilateral inflammation/hyperalgesia: possible involvement of noradrenergic mechanisms

    Eur. J. Pharmacol.

    (1991)
  • M.J. Iadarola et al.

    Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: stimulus specificity behavioral parameters and opioid receptor binding

    Pain

    (1988)
  • L. Isaac et al.

    MK-801 blocks dynorphin A (1–13)-induced loss of the tail-flick reflex in the rat

    Brain Res.

    (1990)
  • S. Jeftinija

    Excitatory transmission in the dorsal horn is in part mediated through APV-sensitive NMDA receptors

    Neurosci. Lett.

    (1989)
  • J. Joris et al.

    Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia

    Pain

    (1990)
  • K.C. Kajander et al.

    Dynorphin increases in the dorsal spinal cord in rats with a painful peripheral neuropathy

    Peptides

    (1990)
  • A.E. King et al.

    An intracellular analysis of amino acid induced excitations of deep dorsal horn neurones in the rat spinal cord slice

    Neurosci. Lett.

    (1988)
  • P. Klepstad et al.

    Evidence of a role for NMDA receptors in pain perception

    Eur. J. Pharmacol.

    (1990)
  • S. Lei et al.

    Effects of excitatory amino acids (EAA) and μ opioid agonists on nociceptive projection neurons in rat

    Pain (Suppl.)

    (1990)
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