Inhalation of Protium heptaphyllum (Aubl.) Marchand (BREU-BRANCO) essential oil as an analgesic and anxiolytic in fibromyalgia. Case reports

ABSTRACT

BACKGROUND AND OBJECTIVES:  Fibromyalgia (FM) refers to a chronic pain condition with a multifactorial etiology, which negatively impacts the lives of its sufferers and is often refractory to conventional treatment. The aim of this study is to report a series of cases using Protium heptaphyllum (OEBB) essential oil to control pain and anxiety in FM sufferers.

CASE REPORTS:  This is a case series of an experimental, open and self-controlled study aimed at proving the efficacy and relevance of using aromatherapy via inhalation to improve the quality of life of women with fibromyalgia (FM). For this purpose, the essential oil obtained by steam distillation of resin OEBB was used. Five women over the age of 50 with a confirmed medical diagnosis and insufficient treatment with traditional therapies were selected to verify the efficacy of inhaling OEBB essential oil. The patients were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and the visual analog scale (VAS) before and after aromatherapy and the results were compared using the T-test for two related samples. The evidence showed that OEBB inhalation was not effective in reducing the intensity of pain crises (p>0.05). However, there was evidence of benefits in relation to improvements in quality of life, such as an increase in disposition, improvement in mood, restorative sleep and a reduction in anxiety in 46.78% (p<0.01), as demonstrated by the score obtained on the FIQ.

CONCLUSION:  It can be concluded that aromatherapy via inhalation has a positive effect on controlling the comorbidities caused by fibromyalgia. Furthermore, aromatherapy is a complementary practice that should be considered a powerful adjunct to traditional therapies, and its indication should be encouraged by public and private health services.

Keywords:
Aromatherapy; Chronic pain; Fibromyalgia; Smell sense

HIGHLIGHTS

Fibromyalgia is a public health problem that prevents sufferers from working and has a negative impact on society

Emotional factors such as anxiety and depression are involved in the development of chronic pain related to fibromyalgia.

Drugs used to treat fibromyalgia cause significant adverse effects and the search for complementary treatment methods is essential, such as the use of essential oils.

RESUMO

JUSTIFICATIVA E OBJETIVOS:  A fibromialgia (FM) refere-se a uma condição dolorosa crônica com etiologia multifatorial, que impacta negativamente na vida de seus portadores e muitas vezes é refratária ao tratamento convencional. O objetivo do presente estudo foi relatar uma série de casos com uso de óleo essencial de Protium heptaphyllum (OEBB) para controle da dor e ansiedade de fibromiálgicos.

RELATO DOS CASOS:  Trata-se de uma série de casos pertencentes a um estudo experimental, aberto e autocontrolado, objetivando comprovar a eficácia e relevância do uso da aromaterapia via inalatória para a melhoria da qualidade de vida de mulheres portadoras de FM. Para isso, foi utilizado o óleo essencial obtido pela destilação por arraste a vapor da resina de OEBB. Foram selecionadas 5 mulheres acima de 50 anos com diagnóstico médico confirmado e em tratamento insuficiente com as terapêuticas tradicionais para verificar a eficácia da inalação do óleo essencial de OEBB. As pacientes foram avaliadas através do Questionário de Impactos da Fibromialgia (QIF) e da Escala Analógica Visual (EAV) antes e após a aromaterapia e os resultados foram comparados por meio do Teste T para duas amostras relacionadas. As evidências demonstraram que a inalação de OEBB não foi eficaz para diminuir a intensidade das crises álgicas (p>0,05). No entanto, ficaram comprovados benefícios em relação a melhorias na qualidade de vida como aumento da disposição, melhora do ânimo e do humor, sono reparador e diminuição da ansiedade em 46,78% (p<0,01), conforme demonstrado na pontuação obtida no QIF.

CONCLUSÃO:  Conclui-se que a aromaterapia via inalatória apresenta um efeito positivo para controle das comorbidades causadas pela fibromialgia. No mais, a aromaterapia é uma prática complementar que deve ser considerada uma potente adjuvante às terapias tradicionais, devendo sua indicação ser estimulada pelos serviços de saúde públicos e privados.

Descritores:
Aromaterapia; Dor crônica; Fibromialgia; Olfação

DESTAQUES

A fibromialgia é um problema de saúde pública que impede seu portador de desempenhar atividades laborais e impacta negativamente na sociedade

Fatores emocionais, como ansiedade e depressão estão envolvidos no desenvolvimento da dor crônica relacionada à fibromialgia.

Fármacos utilizados para tratamento da fibromialgia causam efeitos adversos importantes e a busca por métodos complementares de tratamento é fundamental, como o uso de óleos essenciais.

INTRODUCTION

Fibromyalgia (FM) is a chronic pain syndrome with a multifacto-rial etiology and a disorder in the processing of painful stimuli1,2 characterized by chronic, diffuse musculoskeletal pain that is, to date, incurable³. It is associated with other chronic conditions such as fatigue, sleep disorders, cognitive disorders, mood swings and various somatic symptoms⁴,⁵. The estimation is that the average prevalence of the population affected by chronic pain (CP) is 45.6%⁶, with official data published in the literature showing that FM affects around 2%-2.5% of the Brazilian population⁷, translating into a universe of 4.1-6.2 million people affected⁸, most of them women of working age⁹. Due to its complexity and multiplicity of causes, no standard treatment has been described, justifying the investigation of complementary methods to traditional therapy¹⁰. In this world, the use of essential oils (EOs) is a promising option, as their medicinal effects have been proven to help physical and psychological well-being¹¹. Among those studied is the one extracted from the distillation of the resin of Protium heptaphyllum (Aubl.) Marchand, also known as almecegueira or breu-branco (OEBB)¹².

The literature shows various biological activities of P. heptaphyllum resin, mainly as a potential anti-inflammatory drugs, muscle relaxant, anxiolytic and antidepressant, with therapeutic effects for pain and mood control¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸. Despite the traditional recognition of its properties, the biological activities of OEBB are still being studied¹⁹. Given the physical, emotional, social and economic impact that FM has, the search for new treatment methods is imperative, underpinning the reported scientific interest. The present study analyzed the effect of inhaling OEBB on pain control and improving the quality of life of FM sufferers, justifying the encouragement and training of aromatherapy in public health services.

CASE REPORT

Five women over the age of 50 (58.4±2.8 years) were selected who had FM with a confirmed medical diagnosis and were being treated insufficiently with traditional therapies (analgesics, steroidal or non-steroidal anti-inflammatory drugs, antidepres-sants, anticonvulsants, opioids, herbal medicines and anesthetic procedures)3.

After an introductory pre-screening meeting and presentation to the OEBB, they were informed that they could leave the experiment at any time. At the time, a WhatsApp group was created for monitoring and prompt guidance.

The inclusion criteria considered were a previous diagnosis of FM, the presence of active CD and the absence of exclusion criteria - pregnant or breastfeeding women, patients with decom-pensated comorbidities (diabetes mellitus, hypertension, heart failure and kidney failure, for example), hemophiliac patients, patients taking platelet antiaggregants or other drugs for coagulation disorders, patients with neurological diseases (personal history of epilepsy or other types of seizures), patients with chronic migraines, as well as those who showed intolerance to the odor of OEBB at presentation or systemic changes in the dose-supervised

The research was authorized by the Research Ethics Committee of the University of Paraná (UNIPAR), CAAE no. 69147823.9.0000.0109. Screening took place at the headquarters of the Fibromyalgia Association of Paraná (APAFIBRO) in the municipality of Umuarama/PR. Virtual meetings were held to clarify matters for those who were unable to attend. All the participants signed an Informed Consent Form for their participation in the research and anonymous disclosure of the results.

Treatment intervention

The intervention protocol, adapted from reference authors²⁰, consists of inhaling 10 drops of OEBB into a personal inhalation device commercially known as an “aromastick” (Figure 1). The participants were instructed to do 10-minute sessions four times a day: the first in the morning, right after waking up; the second, around lunch break (12-14h); the third, in the late afternoon (around 6pm); and finally, before bed, for 14 days. At the end of the agreed period, the participants had to return for a scheduled clinical reassessment and reapplication of the questionnaires. This more informal form of recommendation was designed to: 1) not impact so much on individual routines; 2) ensure better patient adherence to the proposed treatment. At the doctor’s appointment, three standardized forms²² were applied, two of which were generic for investigating and classifying CD, namely: the numerical and colorimetric visual analogue scale (VAS)²³ and the LANSS pain scale²⁴ and one specific to FM, the Fibromyalgia Impact Questionnaire (QIF)25 with scores adapted by Azevedo²⁶.

Figure 1
“Aromastick” personal inhaler. A - “Aromastick” personal inhaler. B - Demonstration of the proposed form of use.

Afterwards, the volunteers were given a personal “aromastick” inhaler already prepared with 10 drops of OEBB and instructions on how to use it correctly, clearing up any doubts. All the participants were instructed on the signs and symptoms which, in case they appeared, they should contact the doctor-researcher and return for an immediate clinical assessment. In order to minimize possible adverse effects, the first dose-supervised inhalation was carried out in the assessment room, where the participants waited for at least 30 minutes to observe and recheck their blood pressure. The data obtained was subjected to descriptive statistics by determining the mean, standard error of the mean and coefficient of variation of the QIF and EAV before and after the intervention with OEBB inhalation. The results were first analyzed for normality (Lilliefors). As the data was normally distributed, the results were compared using Student’s t-test for two related samples, considering a significance level of 5%. In addition, descriptive statistics were carried out on age and the percentage reduction in the QIF score using the Bioestat 5.327 program. No statistical analysis was carried out on the LANNS scale due to the maintenance of the initial and final values found.

Follow-up and outcomes

Regarding the reduction in the intensity and/or duration of pain crises, there were no statistically significant differences in the VAS before and after the intervention with OEBB inhalation (p>0.05) (Table 1).

Table 1
Mean ± standard error of the Visual Analog Scale before and after the intervention with the inhalation of breu-branco essential oil (OEBB).

Descriptive statistics	VAS before	VAS after
Mean ± EP	7.2 ± 0.90	5.7 ± 0.37
CV%	26.72	14.68
P value	0.104

As for the improvement in quality of life, the results were more positive. Before starting the inhalations, the participants scored an average of 82.23±7.22 on the QIF, with an average reduction of 46.78% after the intervention, with an average score of 49.91±7.01 (p<0.01), bringing more spirit and disposition to carry out daily activities, reducing anxiety and insomnia (Table 2). It should be noted that the participants reported a cumulative effect, with improvements felt mainly after the 10th day of use. The results showed that inhaling OEBB proved to be a practical and effective solution for medium-term use to control mood and improve quality of life in FM patients, justifying interest, further research and training for public and private health professionals in aromatherapy.

Table 2
Mean ± standard error of the Fibromyalgia Impact Questionnaire before and after the intervention with the inhalation of breu-bran-co essential oil (OEBB).

Descriptive statistics	QIF before		QIF after
Mean ± EP	82.23±7.22a		49.91±7.01b
CV%	19.63		31.39
P value		0.0073

• ^a-b Means followed by different letters in the row differ according to the Student’s t-test.

Patients perspectives

In the final feedback, one participant reported a significant worsening after stopping the inhalations, feeling constant headaches, depressed mood and body aches. Another reported extreme well-being and relaxation with the aroma, which brought back good memories and a sense of tranquility, and reported improved sleep quality. After the test period, the participants were instructed to stop inhaling for a 7-day break and about the safety and possibility of sporadic use while the personal inhaler was aromatizing.

DISCUSSION

CP is a debilitating condition characterized by generalized mus-culoskeletal pain, persistent for more than three months and without an explainable cause, such as inflammation⁵. This condition has a poor prognosis, negatively affecting patients’ quality of life by impairing sleep, daily activities, mood and social and family relationships²⁸. CP can lead to absence from productive activities, resulting in sick pay or early retirement, which has a significant economic impact²⁹.

Within the context of CP, FM stands out, a chronic rheumatolo-gical disease characterized by diffuse musculoskeletal pain whose cure is still a challenge³. FM involves a disorder in the processing of painful stimuli and is often associated with fatigue, sleep disorders, cognitive disorders and mood swings⁷. Various therapies are used for treatment, including analgesics, anti-inflammatory and antidepressants³, as well as integrative practices such as the use of herbal medicines and medicinal plants³⁰. Among these practices, aromatherapy with EOs has gained popularity and scientific notoriety³¹,³²,³³,³⁴,³⁵,³⁶. Among these, OEBB has recognized anti-inflammatory, muscle relaxant and anxiolytic potential³⁷,³⁸,³⁹, justifying the investigation of its effect on pain control and improving the quality of life of women with FM⁴⁰.

The efficacy of inhaling EOs is possible due to the volatile nature of their compounds, which are both absorbed systematically and through the activation of nasal olfactory chemoreceptors and subsequent signaling, altering the neurophysiological activity of the brain and the neuroendocrine system, providing positive sensations such as emotional well-being, tranquility and relaxation through the release of neurotransmitters such as serotonin, dopamine and gamma-aminobutyric acid (GABA)⁴¹.

The aromatherapeutic route chosen was olfactory therapy, a treatment modality that has not yet been officially explored and is advantageous for the treatment of mental and behavioral disorders and mood disorders such as anxiety, depression and sleep disorders due to the biological activities of the chemical components found in EOs⁴².

No studies evaluating the efficacy of OEBB inhalation for any pathology or comorbidity in humans were found in the medical literature searched in the Virtual Health Library, Google Scholar, Pubmed and Scielo databases, which corroborates the importance of this pilot study. In the end, it was proven that olfactory treatment with OEBB had a non-statistically significant influence on reducing pain sensation (p>0.05); however, it was able to improve the quality of life of patients with FM (p<0.01). Despite widespread availability and easy commercial access, it is important to note that the use of EOs is not without risk and should be monitored by a trained professional aromatherapist.

CONCLUSION

OEBB showed hypertensive potential and should be used with caution in patients with heart disease and/or hypertension; thus, the present study suggests caution in the use of OEBB in patients with nephropathy and/or any other vasculopathies. As this is a small sample involving a restricted target audience (women over 50), the suggestion is for further more extensive and detailed studies to prove the clinical findings and demonstrate the safety of long-term use of OEBB.

• Sponsoring sources:
  none.

ACKNOWLEDGEMENTS

The authors would like to think Curumin da Amazônia for its willingness to donate the breu-branco resin for the extraction of the essential oil used in this clinical trial; the State University of Maringá (UEM) for its technical support and for carrying out the extraction and chemical characterization of the essential oil, specially Prof. Dr. Cristiane Mengue Feniman Moritz; the Paraná Fibromyalgia Association (APAFIBRO), in the person of Rosely Sucupira, its representative in the city of Umuarama/PR, for agreeing to take part in this experiment; the Physiotherapy Clinic in the person of Dr. Ana Luiza Rezende Nabhan for her help and willingness to publicize the project and mediate the meeting with the volunteers; each participant with such a disastrous condition who voluntarily agreed to follow the proposed intervention protocol.

REFERENCES

• ¹ Winslow, BT, Vandal C, Dang, L. Fibromyalgia: diagnosis and management. Am Fam Physician. 2023;107(2):137-44.
• ² Siracusa R, Paola RD, Cuzzocrea S, Impellizzeri D. Fibromyalgia: pathogenesis, mechanisms, diagnosis and treatment options update. Int J Mol Sci. 2021;22(8):3891.
• ³ Brasil, Ministério da Saúde. Relatório de Recomendação — Protocolos clínicos e diretrizes terapêuticas: dor crônica [Internet]. Brasília, 2022 Oct [cited 2024 Mar 18]. Available from: https://www.gov.br/conitec/pt-br/midias/consultas/relato-rios/2022/20221101_pcdt_dor_cronica_cp74.pdf.
  » https://www.gov.br/conitec/pt-br/midias/consultas/relato-rios/2022/20221101_pcdt_dor_cronica_cp74.pdf.
• ⁴ Provenza JR, Pollak DF, Martinez JE, Paiva ES, Helfenstein M, Heymann R, Matos JMC, Souza EJR. Fibromialgia. Rev Bras Reumatol. 2004;44(6):443-9.
• ⁵ Kanematsu JS, Atanazio B, Cunha BF, Caetano LP, Arada DMY. Impacto da dor na qualidade de vida do paciente com dor crônica. Rev Med. 2022;101(3):e-192586.
• ⁶ Aguiar, DP, Souza, CP, Barbosa, WJ, Santos-Júnior, FF, Oliveira AS. Prevalência de dor crônica no Brasil: revisão sistemática. BrJP. 2021;4(3):257-67.
• ⁷ Heymann RE, Paiva ES, Helfenstein Junior M, Pollak DF, Martinez JE, Provenza JR, Paula AP, Allthoff AC, Souza EJR, Neubarth F, Lage LV, Rezende MC, Assis MR, Lopes MLL, Kaziyama HHS, Yeng LT, Iamamura M, Saron TRP, Nascimento OJM, Fonseca MCM. Consenso brasileiro do tratamento da fibromialgia. Rev Brasil Reu- matol. 2010;50(1):56-66.
• ⁸ Instituto Brasileiro de Geografia e Estatística (IBGE). Censo Brasileiro de 2022 [Internet]. Rio de Janeiro: IBGE, 2022 [cited 2023 Aug 10]. Available from: https://www.ibge.gov.br/estatisticas/sociais/trabalho/22827-censo-demografico-2022.html.
  » https://www.ibge.gov.br/estatisticas/sociais/trabalho/22827-censo-demografico-2022.html.
• ⁹ Souza JB, Perissinotti DM. The prevalence of fibromyalgia in Brazil: a population-based study with secondary data of the study on chronic pain prevalence in Brazil. BrJP. 2018;18(4):345-8.
• ¹⁰ Oliveira Júnior JO, Almeida MB. The current treatment of fibromyalgia. BrJP 2018;1(3):255-62.
• ¹¹ Brasil, Ministério da Saúde. Portaria n° 702, de 21 de março de 2018. Altera a Portaria de Consolidação n° 2/GM/MS, de 28 de setembro de 2017, para incluir novas práticas na Política Nacional de Práticas Integrativas e Complementares-PNPIC. Diário Oficial da União [Internet]. 2018 [cited 2023 Mar 23]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/gm/2018/prt0702_22_03_2018.html.
  » https://bvsms.saude.gov.br/bvs/saudelegis/gm/2018/prt0702_22_03_2018.html.
• ¹² Reflora. Burseraceae in Flora e Funga do Brasil [Internet]. Rio de Janeiro, RJ: Jardim Botânico do Rio de Janeiro. 2023 [cited 2023 Jun 16]. Available from: https://floradobrasil.jbrj.gov.br/FB6593.
  » https://floradobrasil.jbrj.gov.br/FB6593.
• ¹³ Carvalho PER. Espécies arbóreas brasileiras espécies arbóreas brasileiras. Almecegueira: Protium heptaphyllum. Brasília, DF: EMBRAPA [Internet]. 2006 [cited 2023 Feb 6];2; 11 p. Available from: https://ainfo.cnptia.embrapa.br/digital/bitstream/item/232282/1/Especies-Arboreas-Brasileiras-vol-2-Almecegueira.pdf.
  » https://ainfo.cnptia.embrapa.br/digital/bitstream/item/232282/1/Especies-Arboreas-Brasileiras-vol-2-Almecegueira.pdf.
• ¹⁴ Mannino G, Iovino P, Lauria A, Genova T, Asteggiano A, Notarbartolo M, Porcu A, Serio G, Chinigò G, Occhipinti A, Capuzzo A, Medana C, Munaron L, Gentile C. Bioactive Triterpenes of Protium heptaphyllum Gum Resin Extract Display Cholesterol-Lowering Potential. Int J Mol Sci. 2021;22(5):2664.
• ¹⁵ Mobin M, Lima SG, Almeida LTG, Takahashi JP, Teles JB, Szeszs MW, Martins MA, Carvalho AA, Melhem M. MDGC-MS analysis of essential oils from Protium heptaphyllum (Aubl.) and their antifungal activity against Candida specie. Rev Bras Pl Med. 2016;18(2):531-8.
• ¹⁶ Rocha TS, Santana ALCM, Müller TS, Machado M, Oliveira GL. Chemical variability of essential oils from Protium heptaphyllum. Res Soc Develop. 2022;11(10):e288111032835.
• ¹⁷ Rüdigera AL, Sianib AC, Veiga Unior VF. The Chemistry and Pharmacology of the South America genus Protium Burm. f. (Burseraceae). Pharmacognosy Rev. 2007;1(1):93-104.
• ¹⁸ Vieira Júnior, GM, Carvalho, AA, Gonzaga, WA, Chaves, MH. Cromatografando em coluna com resina de Almécega: Um Projeto Para Química Orgânica Experimental. 2007. Quim Nova. 2007;30(2):491-3.
• ¹⁹ Furtado FB. Caracterização química e atividades biológicas dos óleos essenciais de Protium heptaphyllum, Hedyosmum brasiliense, Blepharocalyx salicifolius, Baccharis dracunculifolia e Nectandra megapotamica. 2018 [cited 2024 Feb 2]. Available from: https://bdtd.ibict.br/vufind/Record/UNSP_ebac69413bd9058a84a0d072f574df67.
  » https://bdtd.ibict.br/vufind/Record/UNSP_ebac69413bd9058a84a0d072f574df67.
• ²⁰ Milioli IAR, de Medeiros GMDS. Efeitos da inalação do óleo essencial Cedrus atlan-tica na dor em fibromiálgicas: ensaio clínico piloto. In Delgado et al. Práticas Integrativas e Complementares: visão holística e multidisciplinar. Editora Científica Digital. 2022;2(1):45-59.
• ²¹ Biorender. BioRender [Internet]. http://www.biorender.com 2024 [cited 2024 Mar 20]. Available from: https://www.biorender.com/.
  » http://www.biorender.com» https://www.biorender.com/.
• ²² Brasil, Ministério da Saúde. Escala de dor LANNS e EVA [Internet] 2016 [cited 2023 Mar 23]. Available from: http://www.as.saude.ms.gov.br/wp-content/uploads/2016/04/Escala-de-dor-LANNS-E-EVA.pdf.
  » http://www.as.saude.ms.gov.br/wp-content/uploads/2016/04/Escala-de-dor-LANNS-E-EVA.pdf.
• ²³ Goiás (Estado). Secretaria de Estado da Saúde. Central Estadual de Medicamentos de Alto Custo (CEMAC). ANEXO I - Escala Visual Analógica - EVA [Internet]. 2020 Jun 1 [cited 2023 Sept 2]. Available from: https://www.saude.go.gov.br/files/cemac/documentos-e-orientacoes/ANEXOI-EscalaEVA.pdf
  » https://www.saude.go.gov.br/files/cemac/documentos-e-orientacoes/ANEXOI-EscalaEVA.pdf
• ²⁴ Brasil, Ministério da Saúde. Escala de dor LANNS (Adaptada ao português do Brasil por Schestatsky et al. 2011). Brasília, DF: 2012 [cited 2023 May 23]. Available from: https://www.as.saude.ms.gov.br/wp-content/uploads/2016/04/Escala-de-dor--LANNS-E-EVA.pdf.
  » https://www.as.saude.ms.gov.br/wp-content/uploads/2016/04/Escala-de-dor--LANNS-E-EVA.pdf.
• ²⁵ Marques, AP, Santos, AMB, Assumpção, A, Matsutani, LA, Lage, LV, Pereira, CAB. Validação da versão brasileira do Fibromyalgia Impact Questionnaire (FIQ). Rev Bras Reumatol. 2006;46(1):24-31.
• ²⁶ Azevedo VF, Paiva ES, Favretto LG, Machado DM, Felippe LRH, Scussel, Ferraz JB, Soares WA, Yagueshita. FIQ Score em pacientes fibromiálgicos com e sem espondilite anquilosante: análise comparativa. Rev Med Res. 2011;13(3). Disponível em: https://www.researchgate.net/profile/Valderilio-Azevedo/publication/234864869_FIQ_sco-re_in_patients_with_fibromyalgia_and_without_ankylosing_spondylitis_compa-rative_analysis/links/554709db0cf234bdb21db04b/FIQ-score-in-patients-with-fi-bromyalgia-and-without-ankylosing-spondylitis-comparative-analysis.pdf. Acesso em 03/10/2024.
  » https://www.researchgate.net/profile/Valderilio-Azevedo/publication/234864869_FIQ_sco-re_in_patients_with_fibromyalgia_and_without_ankylosing_spondylitis_compa-rative_analysis/links/554709db0cf234bdb21db04b/FIQ-score-in-patients-with-fi-bromyalgia-and-without-ankylosing-spondylitis-comparative-analysis.pdf.
• ²⁷ Ayres M, Ayres Júnior M, Ayres DL, Santos SAS. Bio Estat: Aplicações estatísticas nas áreas das ciências biomédicas. Belém: Universidade Federal do Pará [Internet]. 2007 [cited 2023 Dec 9]. 380 p. Available from: https://www.researchgate.net/profile/Alex-De-Assis-Dos-Santos-2/publication/263608962_BIOESTAT_-_aplicacoes_es-tatisticas_nas_areas_das_Ciencias_Bio-Medicas/links/02e7e53b598e69ebfe000000/BIOESTAT-aplicacoes-estatisticas-nas-areas-das-Ciencias-Bio-Medicas.pdf.
  » https://www.researchgate.net/profile/Alex-De-Assis-Dos-Santos-2/publication/263608962_BIOESTAT_-_aplicacoes_es-tatisticas_nas_areas_das_Ciencias_Bio-Medicas/links/02e7e53b598e69ebfe000000/BIOESTAT-aplicacoes-estatisticas-nas-areas-das-Ciencias-Bio-Medicas.pdf.
• ²⁸ Martinez J, Paiva E, Rezende M, Heymann R, Helfenstein M, Ranzolin A, Provenza J, Ribeiro L, Souza E, Feldman D, Assis M. EpiFibro (Registro Brasileiro de Fibromialgia): dados sobre a classificação do ACR e preenchimento dos critérios diagnósticos preliminares e avaliação de seguimento [Internet]. Rev Bras Reumatol. 2017;57:129-33.
• ²⁹ Alberti FF, Blatt CR, Pilger D. Custos diretos e indiretos da fibromialgia: uma revisão de escopo. JBES-Jornal Brasileiro de Economia da Saúde [Internet]. 2021 Dec [cited 2024 2024 Feb 11]. Available from: https://www.researchgate.net/publica-tion/360664515_Custos_diretos_e_indiretos_da_fibromialgia_uma_revisao_de_es-copo.
  » https://www.researchgate.net/publica-tion/360664515_Custos_diretos_e_indiretos_da_fibromialgia_uma_revisao_de_es-copo.
• ³⁰ Ferreira LV, Silva LF, Barbosa SR, Salomão PEA. A eficácia do canabidiol no controle da dor em pacientes com fibromialgia. Rev Multidisciplinar Nordeste Mineiro. 2023;1(1).
• ³¹ Biblioteca Virtual em Saúde (BVS). Mapa de Evidências da Efetividade Clínica da Aromaterapia [Internet]. [cited 2024 Feb 4]. Available from: https://mtci.bvsalud.org/pt/mapa-de-evidencias-efetividade-clinica-da-aromaterapia/.
  » https://mtci.bvsalud.org/pt/mapa-de-evidencias-efetividade-clinica-da-aromaterapia/.
• ³² Melo Filho GL. Estudo sobre a eficácia da aromaterapia no tratamento da ansiedade e/ou hipertensão arterial: uma revisão integrativa de literatura. Braz J Health Rev. 2020;3(3):4040-61.
• ³³ Lyra CSD, Nakai LS, Marques AP. Eficácia da aromaterapia na redução de níveis de estresse e ansiedade em alunos de graduação da área da saúde: estudo preliminar. Fisioter Pesq. 2010;17(1):13-7.
• ³⁴ Nascimento A, Prade ACK. Aromaterapia: o poder das plantas e dos óleos essenciais. Recife: Fiocruz-PE. 2020;2;33p. Available from: https://observapics.fiocruz.br/wp--content/uploads/2020/08/Cuidado-integral-na-Covid-Aromaterapia-ObservaPICS.pdf ISBN 978-65-88180-01-3.
  » https://observapics.fiocruz.br/wp--content/uploads/2020/08/Cuidado-integral-na-Covid-Aromaterapia-ObservaPICS.pdf
• ³⁵ World Health Organization. (2013). WHO traditional medicine strategy: 20142023. World Health Organization [Internet]. 2013. [2023 Apr 25]. Available from: https://www.who.int/publications-detail-redirect/9789241506096.
  » https://www.who.int/publications-detail-redirect/9789241506096.
• ³⁶ Cruz, MS, Santos FDRP, Belfort, MGS, dos Santos, DC; Fernandes, TF, Bussinguer, PRR, Blascovich, HB, Costa, MSC, Franco, AM, dos Anjos RR, Malagutti, GC. Avaliação dos benefícios da aromaterapia em pacientes com fibromialgia: uma revisão bibliográfica. Int J Develop Res. 2020; 10(10):40973-6.
• ³⁷ de Lima EM, Cazelli DS, Pinto FE, Mazuco RA, Kalil IC, Lenz D, Scherer R, de Andrade TU, Endringer DC. Essential oil from the resin of protium heptaphyllum: chemical composition, cytotoxicity, antimicrobial activity, and antimutagenicity. Pharmacogn Mag. 2016;12(Suppl 1):S42-6.
• ³⁸ Lima EM, Nascimento AM, Lenz D, Scherer R, Meyrelles SS, Boëchat GAP, Andrade TU, Endringer DC. Triterpenes from the Protium heptaphyllum resin - chemical composition and cytotoxicity. Rev Bras Farmacognosia. 2014;24(4):399-407.
• ³⁹ Siani AC, Ramos MF, Menezes-de-Lima O Jr, Ribeiro-dos-Santos R, Fernadez-Ferreira E, Soares RO, Rosas EC, Susunaga GS, Guimarães AC, Zoghbi MG, Henriques MG. Evaluation of anti-inflammatory-related activity of essential oils from the leaves and resin of species of Protium. J Ethnopharmacol. 1999;66(1):57-69.
• ⁴⁰ da Silva ER, de Oliveira DR, Fernandes PD, Bizzo HR, Leitão SG. Ethnopharmacolo-gical evaluation of breu essential oils from protium species administered by inhalation. Evid Based Complement Alternat Med. 2017;2017:2924171.
• ⁴¹ Cui J, Li M, Wei Y, Li H, He X, Yang Q, Li Z, Duan J, Wu Z, Chen Q, Chen B, Li G, Ming X, Xiong L, Qin D. Inhalation aromatherapy via brain-targeted nasal delivery: natural volatiles or essential oils on mood disorders. Front Pharmacol. 2022;13:860043.
• ⁴² Baudoux, D. O grande manual da aromaterapia: Bioquímica das moléculas, propriedades farmacológicas e indicações terapêuticas de 100 óleos essenciais. Belo Horizonte: Ed. Lazlo, 2019. 674p.

Edited by

• Associate editor in charge: Vania Maria de Araújo Giaretta https://orcid.org/0000-0003-4231-5054

Publication Dates

• Publication in this collection
  27 Jan 2025
• Date of issue
  2025

History

• Received
  27 Mar 2024
• Accepted
  19 Oct 2024