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IS THE MODULATION EFFECT OF MIDAZOLAM ON MORPHINE INDUCED ANTINOCICEPTION TIME DEPENDENT?

Year 2019, Volume: 5 Issue: 2, 1573 - 1582, 15.08.2019
https://doi.org/10.30569/adiyamansaglik.559772

Abstract

Aim: The aim
of this study was to investigate the effects of midazolam, morphine and
midazolam-morphine on nociception. Benzodiazepines are known to influence
opioid analgesia, and variations can be expected in the interaction between
benzodiazepines and opioids at different times of the day.

Method: The
effects of midazolam, morphine, and midazolam-morphine combination on
nociception were evaluated with tail flick test in mice, with together the
time-dependent changes. Midazolam has not any antinociceptive effect and it
inhibited in a fashion dose-dependent the antinociceptive effect of morphine.

Results: Control
group injected with saline displayed a significant diurnal rhythmicity in the
tail flick test significantly. Saline control group’s response latency at light
hour (at 16.00 h, P < 0.05) was
shorter than that at late dark hour (at 04.00 h) and early morning hour (at
08.00 h). Morphine injected animals had shorter response latencies in light
hours (at 12.00 and 16.00 h, P <
0.01) than at late dark hour (at 04.00 h) and early morning hour (at 08.00 h).
When midazolam was used in combination with morphine, the tail flick response
latencies became significant shorter clearly at every experiment times (P < 0.001), however this inhibition
was slightly lower at 04.00 h than the other hours.







Conclusion: Our
results indicate that midazolam antagonism on morphine antinociception have not
diurnal rhythmicity, however it may only slight decreased at late dark hours of
day.

References

  • 1. Rosland J.H., Hunskaar S., and Hole K. Diazepam attenuates morphine antinociception test-dependently in mice, Pharmacol.Toxicol 1990; 66: 382-386.
  • 2. Matla J. and Langwinski R. Effect of benzodiazepines on the central action of narcotic analgesics. Pol.J Pharmacol.Pharm 1982; 34: 135-144.
  • 3. Shannon H.E., Holtzman S.G., and Davis D.C. Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. J Pharmacol.Exp.Ther 1976; 199: 389-399.
  • 4. Oliverio A., Castellano C., and Puglisi-Allegra S. Opiate analgesia: evidence for circadian rhythms in mice. Brain Res 1982; 249: 265-270.
  • 5. Guney H.Z., Gorgun C.Z., Tunctan B., Uludag O., Hodoglugil U., Abacioglu N., and Zengil H. Circadian-rhythm-dependent effects of L-NG-nitroarginine methyl ester (L-NAME) on morphine-induced analgesia. Chronobiol.Int 1998; 15: 283-289.
  • 6. Pakulska W, Czarnecka E. Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice. Pharmazie. 2001 Jan;56(1):89-91.
  • 7. Daghero AM, Bradley EL, Kissin I. Midazolam antagonizes the analgesic effect of morphine in rats. Anesth Analg 1987; 66: 944-7.
  • 8. Smolensky M.H. and D'Alonzo G.E. Biologic rhythms and medicine. Am J Med 1988; 85: 34-46.
  • 9. Bornschein RL, Crockett RS, Smith RP. Diurnal variations in the analgesic effectiveness of morphine in mice. Pharmacol Biochem Behav 1977; 6: 621-26.
  • 10. Labrecque G. and Vanier M.C. Biological rhythms in pain and in the effects of opioid analgesics. Pharmacol Ther 1995; 68: 129-147.
  • 11. Przewlocki R, Lason W, Konecka AM, Gramsch C, Hertz A, Reid LD. The opioid peptide dynorphin, circadian rhythms, and starvation. Science 1983; 219:71-73.
  • 12. Sawynok,J. GABAergic mechanisms of analgesia: an update, Pharmacol.Biochem.Behav 1987; 26: 463-474.
  • 13. Moreau,J.L. and Fields,H.L. Evidence for GABA involvement in midbrain control of medullary neurons that modulate nociceptive transmission. Brain Res 1986; 397: 37-46.
  • 14. Depaulis,A., Morgan,M.M., and Liebeskind,J.C., GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat. Brain Res 1987; 436: 223-228.
  • 15. Rattan,A.K., McDonald,J.S., and Tejwani,G.A. Differential effects of intrathecal midazolam on morphine-induced antinociception in the rat: role of spinal opioid receptors. Anesth Analg 1991;73: 124-131.
  • 16. Luger,T.J., Hayashi,T., Weiss,C.G., and Hill,H.F., The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats, Eur.J Pharmacol 1995; 275: 153-162.
  • 17. Rady,J.J. and Fujimoto,J.M., Dynorphin A(1-17) mediates midazolam antagonism of morphine antinociception in mice, Pharmacol.Biochem.Behav 1993; 46: 331-339.
  • 18. Rattan, A.K. and Tejwani, G.A. Effect of chronic treatment with morphine, midazolam, and both together on beta-endorphin levels in the rat. Brain Res. Bull 1996; 41: 335-341.
  • 19. Pang C.S., Tsang S.F., Yang J.C. Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice. Life Sci., 68, 943-51 (2001).
  • 20. Wee BE, Turek FW. Midazolam, a short acting benzodiazepine, resets the circadian clock of the hamster. Pharmacol Biochem Behav 1989; 32 (4): 901-6.
  • 21. Koopmans R, Dingemanse J, Danhof M, Horsten GP, van Boxtel C. The influence of dosage time of midazolam on its pharmacokinetics and effects in humans. Clin Pharmacol Ther 1991 50(1): 16-24.
  • 22. Guentert TW. Time-dependence in benzodiazepine pharmacokinetics. Mechanisms and clinical significance. Clin Pharmacokinet 1984; 9(3): 203-10.
  • 23. Lauretti GR, Gomes JM, Reis MP, Pereira NL. Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy. J Clin Anesth. 1999 Dec;11(8):663-8.
  • 24. Cao JL, Ding HL, He JH, Zhang LC, Duan SM, Zeng YM. The spinal nitric oxide involved in the inhibitory effect of midazolam on morphine-induced analgesia tolerance. Pharmacol Biochem Behav. 2005 Mar;80(3):493-503.
  • 25. Wille-Ledon C, Chappuy H, Giraud C, Tréluyer JM, Chéron G. Comparison of a morphine and midazolam combination with morphine alone for paediatric displaced fractures: a randomized study. Acta Paediatr. 2011 Nov;100(11):e203-7.
  • 26. Majidi A, Dinpanah H, Ashoori S, Motamed H, Tabatabaey A. Comparison of morphine-midazolam versus morphine injection for pain relief in patients with limb fractures - a clinical trial. Ulus Travma Acil Cerrahi Derg. 2015 Jan;21(1):22-6.
  • 27. Ito K, Yoshikawa M, Maeda M, Jin XL, Takahashi S, Matsuda M, Tamaki R, Kobayashi H, Suzuki T, Hashimoto A. Midazolam attenuates the antinociception induced by d-serine or morphine at the supraspinal level in rats. Eur J Pharmacol. 2008 May 31;586(1-3):139-44.
  • 28. Song L, Wang S, Zuo Y, Chen L, Martyn JA, Mao J. Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury. Brain Res. 2014 May 20;1564:52-61.
  • 29. Leppert W, Okulicz-Kozaryn I, Kaminska E, Szulc M, Mikolajczak P. Analgesic effects of morphine in combination with adjuvant drugs in rats. Pharmacology. 2014;94(5-6):207-13.

MIDAZOLAM'IN MORFİNE İLİŞKİN MODÜLASYON ETKİSİ ANTİNOKİKASYON ZAMANI BAĞIMLI MI?

Year 2019, Volume: 5 Issue: 2, 1573 - 1582, 15.08.2019
https://doi.org/10.30569/adiyamansaglik.559772

Abstract

Amaç: Bu
çalışmanın amacı, midazolam, morfin ve midazolam-morfin kombinasyonunun
nosisepsiyon üzerindeki etkilerini araştırmaktır. Benzodiazepinlerin opioid
analjezisini etkilediği bilinmektedir ve günün farklı zamanlarında
benzodiazepinler ve opioidler arasındaki etkileşimlerde değişiklikler
beklenebilir. Yöntem: Midazolam, morfin
ve midazolam-morfin kombinasyonunun nosisepsiyon üzerindeki etkileri farelerde
kuyruk flick testi ile birlikte zamana bağlı değişiklikler ile değerlendirildi.
Midazolam'ın antinosiseptif bir etkisi yoktur ve morfinin antinosiseptif
etkisini doza bağlı bir şekilde inhibe eder.



Bulgular: Salin
enjekte edilen kontrol grubu, kuyruk flick testinde anlamlı bir günlük
ritmikliği gösterdi. Tuzlu kontrol grubunun ışık saatindeki (16.00 saatte, P
<0.05) saat gecikme süresi karanlık saatlerde (04.00 saatte) ve sabah
saatlerinde (08.00'de) daha kısa idi. Enjekte edilen morfinler, aydınlık
saatlerde (12.00 ve 16.00 saat, P <0.01) karanlık saatlerin geç saatlerinde
(04.00 saatte) ve sabah saatlerinin (saat 08.00'de) daha kısa tepki gecikme
sürelerine sahipti. Midazolam morfin ile birlikte kullanıldığında, kuyruk
hareket yanıtı gecikme süreleri, her deney zamanında (P <0.001) açıkça
belirgin şekilde kısaldı, ancak bu inhibisyon, diğer saatlere göre 04.00 saatte
biraz daha düşüktü. Sonuç: Morfin
antinosisepsiyonundaki midazolam antagonizmasının günlük ritmik olmadığına
işaret etse de, günün karanlık saatlerinde sadece hafif bir şekilde azalabilir.

References

  • 1. Rosland J.H., Hunskaar S., and Hole K. Diazepam attenuates morphine antinociception test-dependently in mice, Pharmacol.Toxicol 1990; 66: 382-386.
  • 2. Matla J. and Langwinski R. Effect of benzodiazepines on the central action of narcotic analgesics. Pol.J Pharmacol.Pharm 1982; 34: 135-144.
  • 3. Shannon H.E., Holtzman S.G., and Davis D.C. Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. J Pharmacol.Exp.Ther 1976; 199: 389-399.
  • 4. Oliverio A., Castellano C., and Puglisi-Allegra S. Opiate analgesia: evidence for circadian rhythms in mice. Brain Res 1982; 249: 265-270.
  • 5. Guney H.Z., Gorgun C.Z., Tunctan B., Uludag O., Hodoglugil U., Abacioglu N., and Zengil H. Circadian-rhythm-dependent effects of L-NG-nitroarginine methyl ester (L-NAME) on morphine-induced analgesia. Chronobiol.Int 1998; 15: 283-289.
  • 6. Pakulska W, Czarnecka E. Effect of diazepam and midazolam on the antinociceptive effect of morphine, metamizol and indomethacin in mice. Pharmazie. 2001 Jan;56(1):89-91.
  • 7. Daghero AM, Bradley EL, Kissin I. Midazolam antagonizes the analgesic effect of morphine in rats. Anesth Analg 1987; 66: 944-7.
  • 8. Smolensky M.H. and D'Alonzo G.E. Biologic rhythms and medicine. Am J Med 1988; 85: 34-46.
  • 9. Bornschein RL, Crockett RS, Smith RP. Diurnal variations in the analgesic effectiveness of morphine in mice. Pharmacol Biochem Behav 1977; 6: 621-26.
  • 10. Labrecque G. and Vanier M.C. Biological rhythms in pain and in the effects of opioid analgesics. Pharmacol Ther 1995; 68: 129-147.
  • 11. Przewlocki R, Lason W, Konecka AM, Gramsch C, Hertz A, Reid LD. The opioid peptide dynorphin, circadian rhythms, and starvation. Science 1983; 219:71-73.
  • 12. Sawynok,J. GABAergic mechanisms of analgesia: an update, Pharmacol.Biochem.Behav 1987; 26: 463-474.
  • 13. Moreau,J.L. and Fields,H.L. Evidence for GABA involvement in midbrain control of medullary neurons that modulate nociceptive transmission. Brain Res 1986; 397: 37-46.
  • 14. Depaulis,A., Morgan,M.M., and Liebeskind,J.C., GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat. Brain Res 1987; 436: 223-228.
  • 15. Rattan,A.K., McDonald,J.S., and Tejwani,G.A. Differential effects of intrathecal midazolam on morphine-induced antinociception in the rat: role of spinal opioid receptors. Anesth Analg 1991;73: 124-131.
  • 16. Luger,T.J., Hayashi,T., Weiss,C.G., and Hill,H.F., The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats, Eur.J Pharmacol 1995; 275: 153-162.
  • 17. Rady,J.J. and Fujimoto,J.M., Dynorphin A(1-17) mediates midazolam antagonism of morphine antinociception in mice, Pharmacol.Biochem.Behav 1993; 46: 331-339.
  • 18. Rattan, A.K. and Tejwani, G.A. Effect of chronic treatment with morphine, midazolam, and both together on beta-endorphin levels in the rat. Brain Res. Bull 1996; 41: 335-341.
  • 19. Pang C.S., Tsang S.F., Yang J.C. Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice. Life Sci., 68, 943-51 (2001).
  • 20. Wee BE, Turek FW. Midazolam, a short acting benzodiazepine, resets the circadian clock of the hamster. Pharmacol Biochem Behav 1989; 32 (4): 901-6.
  • 21. Koopmans R, Dingemanse J, Danhof M, Horsten GP, van Boxtel C. The influence of dosage time of midazolam on its pharmacokinetics and effects in humans. Clin Pharmacol Ther 1991 50(1): 16-24.
  • 22. Guentert TW. Time-dependence in benzodiazepine pharmacokinetics. Mechanisms and clinical significance. Clin Pharmacokinet 1984; 9(3): 203-10.
  • 23. Lauretti GR, Gomes JM, Reis MP, Pereira NL. Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy. J Clin Anesth. 1999 Dec;11(8):663-8.
  • 24. Cao JL, Ding HL, He JH, Zhang LC, Duan SM, Zeng YM. The spinal nitric oxide involved in the inhibitory effect of midazolam on morphine-induced analgesia tolerance. Pharmacol Biochem Behav. 2005 Mar;80(3):493-503.
  • 25. Wille-Ledon C, Chappuy H, Giraud C, Tréluyer JM, Chéron G. Comparison of a morphine and midazolam combination with morphine alone for paediatric displaced fractures: a randomized study. Acta Paediatr. 2011 Nov;100(11):e203-7.
  • 26. Majidi A, Dinpanah H, Ashoori S, Motamed H, Tabatabaey A. Comparison of morphine-midazolam versus morphine injection for pain relief in patients with limb fractures - a clinical trial. Ulus Travma Acil Cerrahi Derg. 2015 Jan;21(1):22-6.
  • 27. Ito K, Yoshikawa M, Maeda M, Jin XL, Takahashi S, Matsuda M, Tamaki R, Kobayashi H, Suzuki T, Hashimoto A. Midazolam attenuates the antinociception induced by d-serine or morphine at the supraspinal level in rats. Eur J Pharmacol. 2008 May 31;586(1-3):139-44.
  • 28. Song L, Wang S, Zuo Y, Chen L, Martyn JA, Mao J. Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury. Brain Res. 2014 May 20;1564:52-61.
  • 29. Leppert W, Okulicz-Kozaryn I, Kaminska E, Szulc M, Mikolajczak P. Analgesic effects of morphine in combination with adjuvant drugs in rats. Pharmacology. 2014;94(5-6):207-13.
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Seyfullah Oktay Arslan 0000-0001-9328-9373

İşıl Özkoçak Turan This is me 0000-0003-1060-2665

Publication Date August 15, 2019
Submission Date May 2, 2019
Acceptance Date June 11, 2019
Published in Issue Year 2019 Volume: 5 Issue: 2

Cite

AMA Arslan SO, Özkoçak Turan İ. IS THE MODULATION EFFECT OF MIDAZOLAM ON MORPHINE INDUCED ANTINOCICEPTION TIME DEPENDENT?. ADYÜ Sağlık Bilimleri Derg. August 2019;5(2):1573-1582. doi:10.30569/adiyamansaglik.559772