Accessibility / Report Error

Attenuation of visceral pain in mice by the essential oil from Vanillosmopsis arborea bark

O óleo essencial do caule de Vanillosmopsis arborea atenua a dor visceral em camundongos

Abstracts

BACKGROUND AND OBJECTIVES: Vanillosmopsis arborea Baker (Asteraceae) has high economic value and anti-inflammatory properties due the presence of alpha-bisabolol in its bark essential oil. Keeping in view the high content of α-bisabolol in Vanillosmopsis arborea (EOVA) bark essential oil, the aim of our study was to determine whether EOVA mitigates viscer METHOD: Mice (n = 8) were pretreated orally with EOVA (100, 200 e 400 mg/kg) or vehicle, and pain-related behavioral responses to intraperitoneal cyclophosphamide (CPM 400 mg/kg), intracolonic mustard oil (MO 0.75%) or capsaicin (CAP 0.3%) were analyzed. RESULTS: Animals that received CFM, OM or CAP presented spontaneous nociceptive behaviors that were significantly suppressed by EOVA. CONCLUSION: These findings point to visceral antinociceptive properties of EOVA suggesting the potential use of Vanillosmopsis arborea to treat pain associated to gastrointestinal disorders.

Essential oil; Vanillosmopsis arborea; Visceral pain


JUSTIFICATIVA E OBJETIVOS: Vanillosmopsis arborea Baker (Asteraceae) de reconhecido valor econômico que possui propriedades anti-inflamatórias provenientes do sesquiterpeno alfa-bisabolol, presente em teores elevados no óleo essencial de sua madeira. Considerando-se o alto teor de α-bisabolol no óleo essencial do caule de Vanillosmopsis arborea (OEVA). O objetivo deste estudo foi determinar o efeito do OEVA na nocicepção visceral induzida por diversos agentes irritantes. MÉTODO: Camundongos (n = 8) foram pré-tratados por via oral com EOVA (100, 200 e 400 mg/kg) ou veículo e as respostas comportamentais devido a administração de ciclofosfamida (CFM 400 mg/kg; por via intraperitoneal), óleo de mostarda (OM 0,75%; intracolônico) ou capsaicina (CAP 0,3%; intracolônica) foram registradas. RESULTADOS: Os animais que receberam CFM, OM ou CAP manifestaram comportamentos nociceptivos espontâneos que foram significativamente suprimidos nos grupos tratados com OEVA. CONCLUSÃO: Estes achados apontam a propriedade antinociceptiva visceral do óleo essencial do caule de Vanillosmopsis arborea indicando o uso potencial no alívio da dor associada às desordens gastrintestinais.

Dor visceral; Óleo essencial; Vanillosmopsis arborea


ORIGINAL ARTICLE

Attenuation of visceral pain in mice by the essential oil from Vanillosmopsis arborea bark* * Received from University of Fortaleza, CE.

O óleo essencial do caule de Vanillosmopsis arborea atenua a dor visceral em camundongos

Gerlânia de Oliveira LeiteI; Renata Souza SampaioII; Laura Hévila Inocêncio LeiteIII; Irwin Rose Alencar de MenezesIV; José Galberto Martins da CostaIV; Adriana Rolim CamposV

IMSc student in Molecular Bioprospection at Regional University of Cariri, Crato, CE, Brazil

IIResearcher of Regional University of Cariri. Crato, CE, Brazil

IIIStudent of Biological Sciences at Regional University of Cariri, Crato, CE, Brazil

IVProfessor of Regional University of Cariri. Crato, CE, Brazil

VProfessor of University of Fortaleza. Fortaleza, CE, Brazil

Address of correspondence Address of correspondence: Adriana Rolim Campos Vice-Rectory of Research and Post-Graduation University of Fortaleza Av. Washington Soares, 1321 60811-905 Fortaleza, CE, Brazil Phone: +55 85 3477 3274 - Fax: +55 85 3477 3056 E-mail: adrirolim@unifor.br

SUMMARY

BACKGROUND AND OBJECTIVES:Vanillosmopsis arborea Baker (Asteraceae) has high economic value and anti-inflammatory properties due the presence of alpha-bisabolol in its bark essential oil. Keeping in view the high content of α-bisabolol in Vanillosmopsis arborea (EOVA) bark essential oil, the aim of our study was to determine whether EOVA mitigates viscer

METHOD: Mice (n = 8) were pretreated orally with EOVA (100, 200 e 400 mg/kg) or vehicle, and pain-related behavioral responses to intraperitoneal cyclophosphamide (CPM 400 mg/kg), intracolonic mustard oil (MO 0.75%) or capsaicin (CAP 0.3%) were analyzed.

RESULTS: Animals that received CFM, OM or CAP presented spontaneous nociceptive behaviors that were significantly suppressed by EOVA.

CONCLUSION: These findings point to visceral antinociceptive properties of EOVA suggesting the potential use of Vanillosmopsis arborea to treat pain associated to gastrointestinal disorders.

Keywords: Essential oil, Vanillosmopsis arborea, Visceral pain.

RESUMO

JUSTIFICATIVA E OBJETIVOS:Vanillosmopsis arborea Baker (Asteraceae) de reconhecido valor econômico que possui propriedades anti-inflamatórias provenientes do sesquiterpeno alfa-bisabolol, presente em teores elevados no óleo essencial de sua madeira. Considerando-se o alto teor de α-bisabolol no óleo essencial do caule de Vanillosmopsis arborea (OEVA). O objetivo deste estudo foi determinar o efeito do OEVA na nocicepção visceral induzida por diversos agentes irritantes.

MÉTODO: Camundongos (n = 8) foram pré-tratados por via oral com EOVA (100, 200 e 400 mg/kg) ou veículo e as respostas comportamentais devido a administração de ciclofosfamida (CFM 400 mg/kg; por via intraperitoneal), óleo de mostarda (OM 0,75%; intracolônico) ou capsaicina (CAP 0,3%; intracolônica) foram registradas.

RESULTADOS: Os animais que receberam CFM, OM ou CAP manifestaram comportamentos nociceptivos espontâneos que foram significativamente suprimidos nos grupos tratados com OEVA.

CONCLUSÃO: Estes achados apontam a propriedade antinociceptiva visceral do óleo essencial do caule de Vanillosmopsis arborea indicando o uso potencial no alívio da dor associada às desordens gastrintestinais.

Descritores: Dor visceral, Óleo essencial, Vanillosmopsis arborea.

INTRODUCTION

Vanillosmopsis arborea Baker, popular known as "candeeiro", is a small tree which grows in the Araripe National Forest, in the state of Ceará, Brazil. Its wood has a strong odor of chamomile and burns easily with a strong flame1. Phytochemical studies of the essential oil revealed the presence of a high content of bisabolol2 and experimental investigations demonstrated the gastroprotective3, larvicidal4, antimicrobial, antifungical and anti-inflammatory activities5 and it is popularly used as a repellent. Earlier studies indicated that candeeiro is not potentially toxic6.

Visceral pain is the most common form of pain for which the patients often seek medical care. Despite the considerable advances in knowledge regarding the basic mechanisms underlying the visceral pain and visceral hyperalgesia, no new effective therapies for abdominal pain have been discovered. So far, there is no experimental evidence indicating a visceral antinociceptive activity of Vanillosmopsis arborea essential oil. An analgesic effect of "candeeiro" using the acetic acid-induced writhing test has been described earlier7, but not considered a valid model of visceral nociception since it affects unknown somatic and visceral structures8. An alternative model of acute visceral pain in the mouse employs the intracolonic instillation of capsaicin, mustard oil or formalin or intraperitoneal cyclophosphamide, that produce visceral pain-related behaviors such as licking of the abdomen, stretching the abdomen, squashing of the lower abdomen against the floor and abdominal retractions, which can be quantified8,9.

Keeping in view the high content of alpha-bisabolol in Vanillosmopsis arborea bark essential oil, the aim of our study was to determine whether Vanillosmopsis arborea mitigates visceral nociception-induced by different noxious agents.

METHOD

Plant material

The essential oil from Vanillosmopsis arborea Baker bark (EOVA) was obtained at the Natural Products Research Laboratory of Regional University of Cariri the composition (w/w) of EOVA revealed the presence of α-bisabolol to extent of 70%. Others identified compounds were α-cadinol (8.4%), elemicine (6.21%), β-bisabolene (4.46%), δ-guaiene (2.31%), β-cubebene (1.76%) and estragole (1.08%).

Animals

Male Swiss albino mice (20-25 g) obtained from the Central Animal House of Regional University of Cariri were used. They were housed in environmentally controlled conditions (22º C, 12 h light-dark cycle), with free access to standard pellet diet (Purina, São Paulo, Brazil) and water. Animals were kept in cages with raised floors to prevent coprophagy. They were fasted over a period of 15 h and were habituated to the test environment for 2 h before the experimentation. The experimental protocols were approved by the Animal Care and Use Committee of the University of Fortaleza in accordance with the ethical guidelines of National Institute of Health, Bethesda, U.S.A.

Cyclophosphamide-induced visceral nociception

Mice divided in groups (8 in each) were treated with vehicle (2% Tween 80 in distillated water, 10 ml/kg, p.o.) or EOVA (100, 200 or 400 mg/kg, p.o.), 1 h before the intraperitoneal administration of cyclophosphamide (CPM, 400 mg/kg). Immediately after CPM or saline injection, each animal was examined for the time spent in expressing the visceral nociceptive behaviors (transient crises) like piloerection, licking the abdomen, squashing of the abdomen against the floor and the abdominal contortions and retractions) during a 4 h period. A normal control, that received only saline intraperitoneally, was included in the study.

Mustard oil-induced visceral nociception

To assess the antinociceptive effect of EOVA against the mustard oil (MO)-induced visceral nociception, mice in groups (n = 8) were orally treated with EOVA (100, 200 or 400 mg/kg) or vehicle (2% Tween 80 in distillated water, 10 ml/kg, p.o.) 1h before the intracolonic administration of MO (0.75% in saline 0.9%, 50 µl/animal). A group of normal control received a similar dose of saline (10 mL/kg). Immediately following the intracolonic MO or saline administration, the mice were observed of the total number of nociceptive behaviors (licking the upper abdomen, stretching the abdomen, squashing the abdomen against the floor and retraction of the abdomen characterized for an arched position), for a 20 min period.

Capsaicin-induced visceral nociception

Male mice divided into groups of eight in each were pretreated with the vehicle (2% Tween 80 in distillated water, 10 ml/kg, p.o.) or EOVA (100, 200 or 400 mg/kg, p.o.). One hour after oral and 30 min following systemic treatments, capsaicin (0.3% in a solution of PBS: Tween 80: ethanol (8:1:1) was instilled into the colon (50 µl/animal) using a fi ne cannula (1.6 mm external diameter), 4 cm far from the anal sphincter. Solid petroleum jelly was applied onto the perianal region to avoid local nerve stimulation. The animals were then observed during a 30 min period for the spontaneous visceral pain-related behaviors (licking the upper abdomen, abdominal contortion and retraction, squashing the abdomen against the floor). A normal group, that received only saline intracolonically, was also included.

Statistical analysis

The results are expressed as mean ±S.E.M. from 8 mice per group. For statistical analysis, ANOVA followed by Student Newman Keul's post hoc test, as appropriate were used. A p < 0.05 was considered statistically significant.

RESULTS

Graphics 1, 2 and 3 show the antinociceptive effect of EOVA in cyclophosphamide, mustard oil and capsaicin tests. Intraperitoneal application of cyclophosphamide (CFM 400 mg/kg) and intracolonic application of mustard oil (MO 0.75%), and capsaicin (CAP 0.3%), provoked a signifi cant increase in spontaneous pain-related behaviors when compared with saline treated normal controls. In groups pretreated with EOVA, cyclophosphamide, mus- tard oil and capsaicin-induced nociceptive behaviors were signifi cantly inhibited.




DISCUSSION

In animals several algogenic substances like capsaicin, mustard, and cyclophosphamide, applied to visceral structures can elicit pain-related behaviors involving capsaicin sensitive primary afferents9. These algogenic substances are capable of inducing pain as well as inflammatory reaction when either visceral afferents are sensitized or central neurons undergo a change in excitability (central sensitization) after persistent visceral input10. In the search for novel natural substances, which possess visceral antinociceptive property, we used the acute models of visceral pain induced by intraperitoneal administration of acetic acid or cyclophosphamide or by intracolonic instillation of mustard oil, capsaicin or formalin to produce spontaneous pain-related behaviors in mice, which has disease-relevancy to human irritable bowel syndrome.

The essential oil of Vanillosmopsis arborea could significantly suppress the pain-related behaviors against all noxious agents used to induce visceral pain, possibly regulating the functioning of primary afferent fibers. Visceral afferents express a wide range of membrane receptors (including vanilloid receptors, TRPV1) to chemical stimuli, which are involved in sensory signaling from the gut to the central nervous system11. This antinociceptive effect may be related to the high bisabolol content in EOVA, since that Alves et al.12 have just reported that bisabolol is able to reduce the neuronal excitability in a concentration-dependent manner.

CONCLUSION

In conclusion, we provided in vivo evidence to show that EOVA inhibits visceral nociception induced by several agents, which needs further elucidation on its antinociceptive activity.

Presented in November 14, 2010.

Accepted in March 28, 2011.

  • 1. Matos MEO, Sousa MP, Matos FJA, et al. Sesquiterpenes from Vanillosmopsis arborea J Nat Prod 1998;51:780-2.
  • 2. Kamatou GPP, Viljoen AM. A review of the application and pharmacological properties of α-bisabolol and α-bisabolol-rich oils. J Am Oil Chem Soc 2010;87(1):1-7.
  • 3. de O Leite G, da Penha AR, Fernandes CN, et al. Gastroprotective mechanism of Vanillosmopsis arborea bark essential oil. Fitoterapia 2009;80(1):77-80.
  • 4. Furtado RF, Lima MGA, Andrade Neto M, et al. Atividade larvicida de óleos essenciais contra Aedes aegypti L. (diptera: culicidae). Neotrop Entomol 2005;34(5):843-7.
  • 5. Lima IVM, Silva MGV, Cavalcanti FS. Estudo químico de Vanillosmopsis arborea - Fonte Cearense de α-bisabolol. in: XLVI Congresso Brasileiro de Química - 46ş CBQ, Salvador, Livro de Resumos; 2006.
  • 6. Mota ML. Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE um modelo murino - Plasmodium beghei. Dissertação de Mestrado. Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal da Paraíba, Brasil; 2009.
  • 7. Santos NKA, Verificação das Propriedades Antibacteriana e Farmacológica do Óleo Essencial de Vanillosmopsis arborea (Asteraceae) Baker. Dissertação de Mestrado. Programa de Pós-Graduação em Bioprospecção Molecular, Universidade Regional do Cariri, Brasil; 2009.
  • 8. Laird JM, Martinez-Caro L, Garcia-Nicas E, et al. A new model of visceral pain and referred hyperalgesia in the mouse. Pain 2001;92(3):335-42.
  • 9. Jiang MC, Gebhart GF. Development of mustard oil-induced hyperalgesia in rats. Pain 1998;77(3):305-13.
  • 10. Olivar T, Laird JM. Cyclophosphamide cystitis in mice: behavioural characterisation and correlation with bladder inflammation. Eur J Pain 1999;3(2):141-9.
  • 11. Maggi CA, Lecci A, Santicioli P, et al. Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents. J Auton Nerv Syst 1992;38(3):201-8.
  • 12. Alves Ade M, Gonçalves JC, Cruz JS, et al. Evaluation of the sesquiterpene (-)-alpha-bisabolol as a novel peripheral nervous blocker. Neurosci Lett 2010;472(1):1-5.
  • 13. Wood JN. Recent advances in understanding molecular mechanisms of primary afferent activation. Gut 2004;53(Suppl 2):9-12.
  • Address of correspondence:
    Adriana Rolim Campos
    Vice-Rectory of Research and Post-Graduation University of Fortaleza
    Av. Washington Soares, 1321
    60811-905 Fortaleza, CE, Brazil
    Phone: +55 85 3477 3274 - Fax: +55 85 3477 3056
    E-mail:
  • *
    Received from University of Fortaleza, CE.
  • Publication Dates

    • Publication in this collection
      28 Sept 2011
    • Date of issue
      Mar 2011

    History

    • Accepted
      28 Mar 2011
    • Received
      14 Nov 2010
    Sociedade Brasileira para o Estudo da Dor Av. Conselheiro Rodrigues Alves, 937 cj 2, 04014-012 São Paulo SP Brasil, Tel.: (55 11) 5904 3959, Fax: (55 11) 5904 2881 - São Paulo - SP - Brazil
    E-mail: dor@dor.org.br