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SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI

Year 2017, Volume: 26 Issue: 1, 52 - 59, 01.03.2017

Abstract

Bu çalışmada, 0.3, 1 ve 3 mg/kg (p.o.) rosmarinik asitin
farelerde santral analjezik etkinliğinin sıcak-plaka ve
kuyruk-batırma testleri, periferal analjezik etkinliğinin
ise asetik asit ile indüklenen kıvranma-testi ile değerlendirilmesi planlanmıştır. Ayrıca bu etkinliğe 5HT2A/2C
reseptör antagonisti ketanserin (1 mg/kg, i.p.) kullanılarak serotonerjik ve α2-adrenerjik antagonisti yohimbin (1 mg/kg, i.p.) kullanılarak noradrenerjik
modülasyonun katkısının araştırılması amaçlanmıştır.
Sıcak-plaka testinde 1 mg/kg rosmarinik asit 45. dakikada, 3 mg/kg rosmarinik asit ise 30., 45. ve 60. dakikada, kuyruk-batırma testinde 1 ve 3 mg/kg rosmarinik
asit 45 ve 60. dakikada termal uyarana karşı verilen
cevabının süresini uzatmıştır. Kıvranma-testinde ise,
45. dakikada uygulanan rosmarinik asit tüm dozlarda
kıvranma sayılarını anlamlı olarak azaltmıştır. Ketanserin, rosmarinik asitin oluşturduğu etkiyi sıcak-plaka
ve kıvranma-testinde değiştirmemiş, kuyruk-batırma
testinde ise anlamlı olarak geri çevirmiştir. Yohimbin,
rosmarinik asitin oluşturduğu etkiyi sıcak-plaka
testinde göreceli olarak, kuyruk-batırma ve kıvranma- testinde ise anlamlı olarak geri çevirmiştir. Rosmarinik
asit hem inici inhibitör yolakta yer alan serotonerjik ve
noradrenerjik sistemi değişik düzeylerde modüle
ederek, hem de periferik noradrenerjik sistemi stimüle
ederek santral ve periferal analjezik etki sağlamaktadır.
Sonuç olarak, ağrının eşlik ettiği rahatsızlıklarda yardımcı ilaç olarak kullanılabilecek doğal bir ilaç adayıdır.

References

  • Zareba G. Phytotherapy for pain relief. Drugs Today (Barc) 2009; 45: 445-467.
  • Süzer Ö. Premium Farmakoloji (3. baskı). Klinisyen Tıp Kitapevleri, Ankara 2005; pp 241-534.
  • Mehrotra A, Shanbhag R, Chamallamudi MR, et al. Ameliorative effect of caffeic acid against inflammatory pain in rodents. Eur J Pharmacol 2011; 666: 80-86.
  • Guginski G, Luiz AP, Silva MD, et al. Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacol Biochem and Behavior 2009; 93 (1): 10-16.
  • Lucarini R, Bernardes WA, Ferreira DS, et al. In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts rosmarinic acid and its acetyl ester derivative. Pharm Biol 2013; 51: 1087-1090.
  • Hasanein P, Mohammad Zaheri L. Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats. Pharm Biol 2014; 52: 1398-1402.
  • Kwon M, Altin M, Duenas H, et al. The role of descending inhibitory pathways on chronic pain modulation and clinical implications. Pain Pract 2014; 14: 656-667.
  • Eddy NB, Leimback D. Synthetic analgesics II Dithienylbutenyl and dithienylbutylamines. J Pharmacol Exp Ther 1953; 107: 385-393.
  • Schmauss C, Yaksh TL. In vivo studies on spinal receptor systems mediating antinociception II Pharmacological profiles suggesting a differential association of mu delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther 1984; 228: 1-12.
  • Koster R, Anderson M, Beer EJ. Acetic acid for analgesic screening. Fed Proc 1959; 18: 412.
  • Flores JA, El Banoua F, Galan -Rodriguez B, et al. Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors. Pain 2004; 110: 205–214.
  • Boonyarikpunchai W, Sukrong S, Towiwat P. Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl. Pharmacol Biochem Behav 2014; 124: 67- 73.
  • Schaible HG. Peripheral and central mechanisms of pain generation. Handb Exp Pharmacol 2007; 177: 3-28.
  • Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 2010; 120: 3779-3787.
  • Pertovaara A, Almeida A. Descending inhibitory system. In: Cervero F, Jensen TS (eds), Endogenous Pain Modulation Handbook of Clinical Neurology. Elsevier, Amsterdam 2006; pp 179-192.
  • Silveira JW, Dias QM, Del Bel EA, et al. Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats. Mol Pain 2010; 6: 17.
  • Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006; 80: 53-83.
  • Kayaalp O, Uzbay T. Santral sinir sistemi Farmakolojisinin temelleri. In: Kayaalp O (eds), Rasyonel Tedavi Yönünden Tıbbi Farmakoloji (13. baskı). Taş Kitapevi, Ankara 2009; pp 664.
  • Dogrul A, Uzbay IT. Topical clonidine antinociception. Pain 2004; 111 (3): 385-391.
  • Binder W, Mousa SA, Sitte N, et al. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue. Eur J Neurosci 2004; 20: 92-100.
  • Petersen M, Simmonds MS. Rosmarinic acid. Phytochem 2003; 62: 121–125.

The Participation of Serotonergic and Noradrenergic Modulation in Rosmarinic Acid-Induced Analgesia

Year 2017, Volume: 26 Issue: 1, 52 - 59, 01.03.2017

Abstract

It was aimed to evaluate the central analgesic activity of
0.3, 1 and 3 mg/kg (p.o.) rosmarinic acid in mice by hot- plate and tail-immersion tests in a time dependent
manner and the peripheral analgesic activity by acetic
acid-induced writhing-test. Furthermore one of the
other purpose of the study is to research the involvement of serotonergic and noradrenergic modulation on
rosmarinic acid-induced analgesia by using 1 mg/kg
(i.p.) ketanserin, 5HT2A/2C receptor antagonist, and yohimbine, α2-adrenoceptor antagonist, respectively. The
enhanced withdrawal responses to thermal stimuli
were observed 45 minutes after the administration of 1
mg/kg rosmarinic acid; 30, 45 and 60 minutes after the
administration of 3 mg/kg rosmarinic acid in hot-plate
test; 45 and 60 minutes after the administration of 1
and 3 mg/kg rosmarinic acid in tail-immersion test. In
writhing-test, the number of writhing significantly decreased 45 minutes after the administration of 0.3, 1
and 3 mg/kg rosmarinic acid. Rosmarinic acid-induced
antinociception was significantly reversed by ketanserin only in tail-immersion test while it was reversed
significantly in both tail-immersion and writhing-test
by yohimbine. Rosmarinic acid provides analgesic effects by modulating serotonergic and noradrenergic
systems that are located in descending inhibitory pathway and by stimulating peripheral noradrenergic system. Therefore, rosmarinic acid is a natural agent that
can be used safely as a co-adjuvant in pain management

References

  • Zareba G. Phytotherapy for pain relief. Drugs Today (Barc) 2009; 45: 445-467.
  • Süzer Ö. Premium Farmakoloji (3. baskı). Klinisyen Tıp Kitapevleri, Ankara 2005; pp 241-534.
  • Mehrotra A, Shanbhag R, Chamallamudi MR, et al. Ameliorative effect of caffeic acid against inflammatory pain in rodents. Eur J Pharmacol 2011; 666: 80-86.
  • Guginski G, Luiz AP, Silva MD, et al. Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacol Biochem and Behavior 2009; 93 (1): 10-16.
  • Lucarini R, Bernardes WA, Ferreira DS, et al. In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts rosmarinic acid and its acetyl ester derivative. Pharm Biol 2013; 51: 1087-1090.
  • Hasanein P, Mohammad Zaheri L. Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats. Pharm Biol 2014; 52: 1398-1402.
  • Kwon M, Altin M, Duenas H, et al. The role of descending inhibitory pathways on chronic pain modulation and clinical implications. Pain Pract 2014; 14: 656-667.
  • Eddy NB, Leimback D. Synthetic analgesics II Dithienylbutenyl and dithienylbutylamines. J Pharmacol Exp Ther 1953; 107: 385-393.
  • Schmauss C, Yaksh TL. In vivo studies on spinal receptor systems mediating antinociception II Pharmacological profiles suggesting a differential association of mu delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther 1984; 228: 1-12.
  • Koster R, Anderson M, Beer EJ. Acetic acid for analgesic screening. Fed Proc 1959; 18: 412.
  • Flores JA, El Banoua F, Galan -Rodriguez B, et al. Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors. Pain 2004; 110: 205–214.
  • Boonyarikpunchai W, Sukrong S, Towiwat P. Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl. Pharmacol Biochem Behav 2014; 124: 67- 73.
  • Schaible HG. Peripheral and central mechanisms of pain generation. Handb Exp Pharmacol 2007; 177: 3-28.
  • Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 2010; 120: 3779-3787.
  • Pertovaara A, Almeida A. Descending inhibitory system. In: Cervero F, Jensen TS (eds), Endogenous Pain Modulation Handbook of Clinical Neurology. Elsevier, Amsterdam 2006; pp 179-192.
  • Silveira JW, Dias QM, Del Bel EA, et al. Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats. Mol Pain 2010; 6: 17.
  • Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006; 80: 53-83.
  • Kayaalp O, Uzbay T. Santral sinir sistemi Farmakolojisinin temelleri. In: Kayaalp O (eds), Rasyonel Tedavi Yönünden Tıbbi Farmakoloji (13. baskı). Taş Kitapevi, Ankara 2009; pp 664.
  • Dogrul A, Uzbay IT. Topical clonidine antinociception. Pain 2004; 111 (3): 385-391.
  • Binder W, Mousa SA, Sitte N, et al. Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue. Eur J Neurosci 2004; 20: 92-100.
  • Petersen M, Simmonds MS. Rosmarinic acid. Phytochem 2003; 62: 121–125.
There are 21 citations in total.

Details

Other ID JA35KT88TD
Journal Section Research Article
Authors

Duygu Aydın This is me

Nurcan Bektaş Türkmen

Rana Arslan This is me

Publication Date March 1, 2017
Submission Date March 1, 2017
Published in Issue Year 2017 Volume: 26 Issue: 1

Cite

APA Aydın, D., Bektaş Türkmen, N., & Arslan, R. (2017). SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI. Sağlık Bilimleri Dergisi, 26(1), 52-59.
AMA Aydın D, Bektaş Türkmen N, Arslan R. SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI. JHS. March 2017;26(1):52-59.
Chicago Aydın, Duygu, Nurcan Bektaş Türkmen, and Rana Arslan. “SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI”. Sağlık Bilimleri Dergisi 26, no. 1 (March 2017): 52-59.
EndNote Aydın D, Bektaş Türkmen N, Arslan R (March 1, 2017) SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI. Sağlık Bilimleri Dergisi 26 1 52–59.
IEEE D. Aydın, N. Bektaş Türkmen, and R. Arslan, “SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI”, JHS, vol. 26, no. 1, pp. 52–59, 2017.
ISNAD Aydın, Duygu et al. “SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI”. Sağlık Bilimleri Dergisi 26/1 (March 2017), 52-59.
JAMA Aydın D, Bektaş Türkmen N, Arslan R. SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI. JHS. 2017;26:52–59.
MLA Aydın, Duygu et al. “SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI”. Sağlık Bilimleri Dergisi, vol. 26, no. 1, 2017, pp. 52-59.
Vancouver Aydın D, Bektaş Türkmen N, Arslan R. SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI. JHS. 2017;26(1):52-9.