Abstract
In this study, we have examined the effects of metamizol (dipyrone), a non-opioid analgesic which is effective in relieving renal colic pain, on nociceptive responses evoked by stimulation of the ureter, on pyeloureteral motility and on intraureter pressure after ureter obstruction in anaesthetised rats. Metamizol (5–50 mg/kg i.v.) dose-dependently inhibited reflex pressor responses evoked by distensions of the ureter to pressures of 30, 55 and 75 mmHg for 30 s (ID50=8±1 mg/kg). Metamizol also dose-dependently reduced intraureter pressure during total ureter occlusion (25 mg/kg produced a reduction of 25% in 10 min). However, metamizol at doses up to 50 mg/kg had no effect on pyleoureteric motility (contraction amplitude, rate or intraureter pressure) under normal pressure conditions. We conclude that metamizol has a direct antinociceptive action on pain of ureteric origin, and spasmolytic effects after ureter obstruction (but not under normal conditions) which may also contribute to pain relief.
Similar content being viewed by others
References
Hetherington JW, Philp NH. Diclofenac sodium versus pethadine in acute renal colic. Brit Med J 1986;292:237–8.
Lloret J, Muñoz J, Monmany J, Puig X, Bonastre M, Brau J, et al. Treatment of renal colic with metamizol: A double-blind comparison with hyocine only or combined with metamizol. Curr Ther Res 1987;42:1119–28.
Muriel-Villoria C, Zungri-Telo E, Díaz-Curiel M, Fernández-Guerrero M, Moreno J, Puerta J, et al. Comparison of the onset and duration of the analgesic effect of metamizol, 1 or 2 g, by the intramuscular or intravenous route, in acute renal colic. Eur J Clin Pharmacol 1995;48:103–7.
Allen JT, Vaughan ED, Gillenwater JY. The effect of indomethacin on renal blood flow and ureteral pressure in unilateral ureter obstruction in awake dogs. Invest Urol 1978;15:324–7.
Perlmutter A, Miller L, Trimble LA, Marion DN, Vaughan ED, Felsen D. Toradol, an NSAID used for renal colic decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction. J Urol 1993;149:926–30.
Santicioli P, Carganico G, Meini S, Giuliani S, Giachetti A, Maggi CA. Modulation by stereoselective inhibition of cyclooxygenase of electromechanical coupling in the guinea-pig isolated renal pelvis. Br J Pharmacol 1995;114:1149–58.
Zwergel U, Zwergel T, Ziegler M: Effects of prostaglandins and prostaglandin synthetase inhibitors on acutely obstructed kidneys in the dog. Urol Int 1991;47:64–9.
Amman R. Neural regulation of ureteric motility. In: Maggi, CA, editor. Nervous control of the urogenital system. 1993:209–25.
Kimoto Y, Constantinou CE. Regional effects of indomethacin, acetyl-salicylic acid and SC-19-220 on the contractility of rabbit pelvis (pacemaker regions and pelviureteric junction). J Urol 1991;146:433–8.
Thulesius O, Angelo-Khattar M. The effect of prostaglandin synthesis inhibition on motility of isolated sheep ureters. Acta Pharmacol Toxicol 1985;56:298–301.
Cervero F. Sensory innervation of the viscera: peripheral basis of visceral pain. Physiol Rev 1994;74:95–138.
Cervero F, Sann H. Mechanically evoked responses of afferent fibres innervating the guinea-pig's ureter: an in vitro study. J Physiol 1989;412:245–66.
Devoghel JC. Small intrathecal doses of lysine-acetylsalicylate relieve intractable pain in man. J Int Med Res 1983;11:90–1.
Malmberg AB, Yaksh TL. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science 1992;257:1276–9.
Neugebauer V, Schaible H-G, He X, Lücke T, Gündling P, Schmidt RF. Electrophysiological evidence for a spinal antinociceptive action of metamizol. Agents Actions 1994;41:62–70.
Willer JC, De Broucher T, Bussel B, Roby-Brami A, Harrewyn JM. Central analgesic effect of ketoprofen in humans: electrophysiological evidence for a supra spinal mechanism in a double-blind and cross-over study. Pain 1989;38:1–7.
McCormack K. The spinal actions of non-steroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects. Drugs 1994;47Suppl5:28–45.
Brogden RN. Pyrazolone derivatives. Drugs 1986;32:60–70.
Brune K, Alpermann H. Non-acidic pyrazoles: Inhibition of prostaglandin production, carrageenan oedema and yeast fever. Agents Actions 1983;13:360–3.
Roza C, Laird JMA. Pressor responses to distension of the ureter in anaesthetised rats: characterisation of a model of acute visceral pain. Neurosci Letts 1995;198:9–12.
Giamberardino MA, Vecchiet L, Albe-Fessard D. Comparison of the effects of ureteral calculosis and occlusion on muscular sensitivity to painful stimulation in rats. Pain 1990;43:227–34.
Giamberardino MA, Valente R, de Bigontina P, Vecchiet L. Artificial ureteral calculosis in rats: behavioural characterisation of the visceral pain episodes and their relationship with referred lumbar muscular hyperalgesia. Pain 1995;61:459–69.
Author information
Authors and Affiliations
Additional information
accepted by K. Brune
Rights and permissions
About this article
Cite this article
Laird, J.M.A., Cervero, F. Effects of metamizol on nociceptive responses to stimulation of the ureter and on ureter motility in anaesthetised rats. Inflamm Res 45, 150–154 (1996). https://doi.org/10.1007/BF02265170
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02265170