Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats

( views:97, downloads:0 )
Author:
MING Xiao-Yun()
WANG Wei()
HAN Ji-Sheng()
LUO Fei()
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 57, Issue 06, 2005
DOI:
Key Word:
tramadol;dihydroetorphine;synergistic effect;analgesia;acute tolerance

Abstract: The present study investigated whether a co-application of tramadol (TRA) and dihydroetorphine (DHE) would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA (in mg) and subcutaneous injection of DHE (in ng) were delivered in fixed proportions (1:6.25, 1:12.5, 1:25, 1:50, 1:100, and 1:200). The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA (20 mg/kg) alone, DHE (1 000 ng/kg) alone, or a combination of TRA (20 mg/kg) and DHE (250 ng/kg) were administered. We found that (1)except for 1 mg: 6.25 ng and 1 mg: 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; (2)the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.

  • [1]Przewlocki R,Przewlocka B.Opioids in chronic pain.Eur J Pharmacol2001; 429 (1-3):79-91.
  • [2]Rushton AR,Sneyd JR.Opioid analgesics.Br J Hosp Med1997; 57 (3):105-106.
  • [3]Mather LE.Trends in the pharmacology of opioids:implications for the pharmacotherapy of pain.Eur J Pain 2001; 5 (Suppl A):49-57.
  • [4]McNicol E,Horowicz-Mehler N,Fisk RA,Bennett K,GialeliGoudas M,Chew PW,Lau J,Carr D; Americal Pain Society.Management of opioid side effects in cancer-related and chronic noncancer pain:a systematic review.J Pain 2003; 4 (5):231-256.
  • [5]Miranda HF,Silva E,Pinardi G.Synergy between the antinociceptive effects of morphine and NSAIDs.Can J Physiol Pharmacol2004; 82 (5):331-338.
  • [6]Satyanarayana PS,Jain NK,Singh A,Kulkarni SK.Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice.Prog Neuropsychopharmacol Biol Psychiatry 2004; 28 (4):641-649.
  • [7]Choe CH,Smith FL.Sedative tolerance accompanies tolerance to the analgesic effects of fentanyl in infant rats.Pediatr Res 2000;47 (6):727-735.
  • [8]Ohmori S,Morimoto Y.Dihydroetorphine:a potent analgesic:pharmacology,toxicology,pharmacokinetics,and clinical effects.CNS Drug Rev 2002; 8 (4):391-404.
  • [9]Aceto MD,Scates SM,Harris LS,Ji Z.Dihydroetorphine:physical dependence and stereotypy after continuous infusion in the rat.Eur J Pharmacol 2000; 387 (1):31-37.
  • [10]Wang DX,Qin BY.Binding of [3H] dihydroetorphine to opioid receptors in rat brain membrane.Chin J Pharmacol 1996; 17 (3):281-283.
  • [11]Lewis JW,Husbands SM.The orvinols and related opioids-high affinity ligands with diverse efficacy profiles.Curr Pharm Desig 2004; 10 (7):717-732.
  • [12]Oliva P,Aurilio C,Massimo F,Grella A,Maione S,Grella E,Scafuro M,Rossi F,Berrino L.The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component.Eur J Pharmacol 2002; 445 (3):179-185.
  • [13]Raffa RB,Friderichs E,Reimann W,ShankRP,CoddEE,Vaught JL.Opioid and nonopioid components independently contribute to the mechanism of action of tramadol,an atypical opioid analgesic.J Pharmacol Exp Ther 1992; 260 (1):275-285.
  • [14]Gibson TP.Pharmacokinetics,efficacy,and safety of analgesia with a focus on tramadol HCl.Am J Med 1996; 101(1A):47S-53S.
  • [15]Miaskowski C,Taiwo YO,Levine JD.Kappa- and delta-opioid agonists synergize to produce potent analgesia.Brain Res 1990;509 (1):165-168.
  • [16]Rossi GC,Pasternak GW,Bodnar RJ.Mu and delta opioid synergy between the periaqueductal gray and the rostro-ventral medulla.Brain Res 1994; 665 (1):85-93.
  • [17]Gessner PK.Isobolographic analysis of interactions:an update on applications and utility.Toxicology 1995; 105 (2-3):161-179.
  • [18]Hao S,Takahata O,Iwasaki H.Isobolographic analysis of interaction between spinal endomophin- 1,a newly isolated endogenous opioid peptide,and lidocaine in the rat formalin test.Neurosci Lett 1999; 276 (3):177-180.
  • [19]Tallarida RJ.A further comment on testing for drug synergism.Pain 1992; 51 (3):381-382.
  • [20]Tallarida RJ.Statistical analysis of drug combinations for synergism.Pain 1992; 49 (1):93-97.
  • [21]Dionne RA,Berthold CW.Therapeutic uses of non-steroidal antiinflammatory drugs in dentistry.Crit Rev Oral Biol Med 2001;12 (4):315-330.
  • [22]Kehlet H.Synergism between analgesics.Ann Med 1995; 27 (2):259-262.
  • [23]Schnitzer T.The new analgesic combination tramadol/acetaminophen.Eur J Anaesthesiol Suppl 2003; 28:13-17.
  • [24]Wang DX,Lu XQ,Qin BY.Dihydroetorphine is a μ-receptorselective ligand.J Pharm Pharmacol 1995; 47 (8):669-673.
  • [25]Orikasa S,Sakurada S,Kisara K.Head-twitch response induced by tyramine.Psychopharmacology (Berl) 1980; 67 (1):53-59.
  • [26]Smialowski A,SmialowskaM,Reichenberg K,ByrskaB,Vetulani J.Motor depression and head twitches induced by IP injection of GABA.Psychopharmacology (Berl) 1980; 69 (3):295-298.
  • [27]Sun HL,Zheng JW,Wang K,Liu RK,Liang JH.Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors.Life Sci 2003; 72 (11):1221-1230.
  • [28]Jolas T,Aghajanian GK.Opioids suppress spontaneous and NMDA-induced inhibitory postsynaptic currents in the dorsal raphe nucleus of the rat in vitro.Brain Res 1997; 755 (2):229-245.
  • [29]Arcioni R,della Rocca M,Romano S,Romano R,Pietropaoli P,Gasparetto A.Ondansetron inhibits the analgesic effects of tramadol:a possible 5-HT3 spinal receptor involvement in acute pain in humans.Anesth Analg 2002; 94 (6):1553-1557.
  • [30]Rojas-Corrales MO,Ortega-Alvaro A,Gibert-Rahola J,RocaVinardell A,Mico JA.Pindolol,a beta-adrenoceptor blocker/5-hydroxytryptamine (1 A/1B) antagonist,enhances the analgesic effect of tramadol.Pain 2000; 88 (2):119-124.
  • [31]Sagata K,Minami K,Yanagihara N,Shiraishi M,Toyohira Y,Ueno S,Shigematsu A.Tramadol inhibits norephinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells.Anesth Analg 2002; 94 (4):901-906.
  • [32]Fairbanks CA,Posthumus IJ,Kitto KF,Stone LS,Wilcox GL.Moxonidine,a selective imidazoline/alpha2 adrenergic receptor agonist,synergizes with morphine and deltorphin Ⅱ to inhibit substance P-induced behavior in mice.Pain 2000; 84 (1):13-20.
  • [33]Fairbanks CA,Stone LS,Kitto KF,Nguyen HO,Posthumus IJ,Wilcox GL.Alpha (2C)-adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy.J Pharmacol Exp Ther 2002; 300 (1):282-290.
  • [34]Bruins Slot LA,Koek W,Tarayre JP,Colpaert FC.Tolerance and inverse tolerance to the hyperalgesic and analgesic actions,respectively,of the novel analgesic,F 13640.Eur J Pharmacol 2003; 466 (3):271-279.
  • [35]Colpaert FC,Tarayre JP,Koek W,Pauwels PJ,BardinL,Xu XJ,Wiesenfeld-Hallin Z,Cosi C,Carilla-Durand E,Assie MB,Vacher B.Large-amplitude 5-HT1A receptor activation:a new mechanism of profound,central analgesia.Neuropharmacology 2002; 43(6):945-958.
  • [36]Xu XJ,Colpaert F,Wiesenfeld-Hallin Z.Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse tolerance.Trends Pharmacol Sci 2003; 24 (12):634-639.
  • [37]Yaksh TL.Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing.Pharmacol Biochem Behav 1985; 22 (5):845-858.
  • [38]Ralth K,Hochhaus G.Drugs used in the treatment of opioid tolerance and physical dependence:a review.Int J Clin PharmacolTher 2004; 42 (4):191-203.
  • [39]Katz WA.Pharmacology and clinical experience with tramadol in osteoarthritis.Drugs 1996; 52 Suppl 3:39-47.
  • [40]Potschka H,Friderichs E,Loscher W.Anticonvulsant and proconvulsant effects of tramadol,its enantiomers and its M1 metabolite in the rat kindling model of epilepsy.Br J Pharmacol 2000; 131 (2):203-212.
  • [41]Neutel JM,Black HR,Weber MA.Combination therapy with diuretics:an evolution of enderstanding.Am J Med 1996; 101(3A):61S-70S.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn