Abstract
Intrathecally administered alpha-2 adrenoceptor and opioid agonists are well known to exert antinociceptive effects in humans and various animals. To examine the interaction of these two groups of agents in the spinal cord, we tested the effect of the opioid antagonists naloxone or naltrindole on the antinociceptive action of an intrathecally administered alpha-2 agonist, dexmedetomidine, using a formalin test in rats. 19 groups of Sprague-Dawley rats (250–300 g) were prepared with chronic intrathecal catheters and examined for the effects of agents on the formalin test. Each group contained 6 animals. 50 μl of 5% formalin was injected subcutaneously in the plantar surface of one hind paw. For each animal, the number of spontaneous flinches, characterized by rapid and brief withdrawal of the injected paw, were counted separately at 1–2 min, 5–6 min (phase 1), and at 5-min intervals thereafter up to 60 min (phase 2). Intrathecal dexmedetomidine (1 μg) maximally depressed the behavioral changes in both phase 1 and phase 2 of the formalin test, which was antagonized by the alpha-2 adrenoceptor selective antagonist atipamezole (0.3 μg). Naloxone (0.1–10 μg) or naltrindole (1–10 μg), when coadministered with dexmedetomidine, showed a dose-dependent antagonism to the effect of dexmedetomidine, whereas naloxone, naltrindole, or atipamezole alone showed no effect on the nocieptive behavior due to formalin injection. These results indicate that the antinociceptive effect of intrathecally administered alpha-2 adrenoceptor agonists may involve opioid receptors in the spinal cord.
Similar content being viewed by others
References
Takano Y, Yaksh TL (1991) Relative efficacy of spinal alpha 2 agonists, dexmedetomidine, clonidine and ST-91, determined in vivo usingN-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, an irreversible antagonist. J Pharmacol Exp Ther 258:438–446.
Takano Y, Yaksh TL (1992) Characterization of the pharmacology of intrathecally administered alpha-2 agonists and antagonists in rats. J Pharmacol Exp Ther 261:764–772
Takano Y, Yaksh TL (1993) Chronic spinal infusion of dexmedetomidine. ST-91 and clonidine: Spinal α2-adrenoceptor subtypes and intrinsic activity. J Pharmacol Exp Ther 264:327–335
Takano Y, Takano M, Yaksh TL (1992) The effect of intrathecally administered imiloxan and WB4101: Possible role of α2 subtypes in the spinal cord. Eur J Pharmacol 219: 465–468
Yaksh TL (1993) The spinal actions of opioids. In: Herz A (ed) Handbook of experimental pharmacology, vol 104/II, Springer, Berlin Heidelberg, pp 53–90
Yaksh TL, Malmberg AB (1994) Interaction of spinal modulatory receptor systems. In: Fields HL, Liebeskind JC (eds) Progress in pain research and management, vol 1. IASP Seattle, pp 151–171
Yaksh TL, Rudy TA (1976) Chronic catheterization of the spinal subarachnoid space. Physiol Behav 7:1032–1036
Reddy SVR, Maderdrut JL, Yaksh TL (1980) Spinal cord pharmacology of adrenergic agonist-mediated antinociception J Pharmacol Exp Ther 213:525–533.
Yaksh TL (1985) Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav 22:845–858
Kendig JJ, Savola MK, Woodley SJ, Maze M (1991) α2-adrenoceptor inhibits a nociceptive response in neonatal rat spinal cord. Eur J Pharmacol 192:293–300
Loomis CW, Jhamandas K, Milne B, Cervenko F (1987) Monoamine and opioid interactions in spinal analgesia and tolerance. Pharmacol Biochem Behav 26:445–451
Sullivan AF, Kalso EA, McQuay HJ, Dickenson AH (1992) The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat. Eur J Pharmacol 215:127–133
Omote K, Kitahata LM, Collins JG, Nakatani K, Nakagawa I (1991) Interaction between opiate subtype and alpha-2 adrenergic agonists in suppression of noxiously evoked activity of WDR neurons in the spinal dorsal horn. Anesthesiology 74:737–743
Milne B, Cerventro F, Jhamandas K, Loomis C, Sutak M (1985) Analgesia and tolerance to intrathecal morphine and norepinephrine infusion via implanted miniosmotic pumps in the rat. Pain 22: 165–172
Stevens CW, Monasky MS, Yaksh TL (1988) Spinal infusion of opiate and alpha-2 agonists in rats: tolerance and cross-tolerance studies. J Pharmacol Exp Ther 244:63–70
Kayser V, Benoist JM, Neil A, Gautron M, Guilbaud G (1988) Behavioral and electrophysiological studies on the paradoxical antinociceptive effects of an extremely low dose of naloxone in an animal model of acute and localized inflammation. Exp Brain Res 73:402–410
Rios L, Jacob J (1983) Local inhibition of inflammatory pain by naloxone and itsn-methyl quaternary analogue. J Pharmacol 96:277–283
Staiman A, Seemans P (1974) The impulse blocking concentrations of anesthetics, alcohols, anticonvulsants, barbiturates and narcotics on phrenic and sciatic nerves. Can J Physiol Pharmacol 52:535–550
Author information
Authors and Affiliations
About this article
Cite this article
Takano, Y., Takano, M., Sato, I. et al. Effects of spinal naloxone and naltrindole on the antinociceptive action of intrathecally administered dexmedetomidine. J Anesth 10, 194–198 (1996). https://doi.org/10.1007/BF02471390
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02471390