Universidade Federal do Ceará
Grupo de Atenção Integral e Pesquisa em Acupuntura e Medicina Tradicional Chinesa – GAIPA UFC

Pesquisa Básica e Plausibilidade Biológica (mechanisms research)

Este tipo de pesquisa, também conhecida como estudo pré-clínico, é desenvolvida para levantar hipóteses e responder perguntas sobre os possíveis mecanismos de ação envolvidos nos efeitos analgésicos, anti-inflamatórios, dentre outros,  dos métodos e recursos terapêuticos. Ou seja, busca encontrar explicações e uma sustentação teórica sobre a plausibilidade biológica das intervenções em saúde. Apresentamos abaixo alguns dos principais estudos que incluem pesquisas comportamentais e de neuroimagem em humanos, bem como pesquisas moleculares, celulares e fisiológicas em modelos animais.

Unitermos: acupoints; acupuncture; biomarker; neuroscience; somatosensation.

Acupuntura

Efeito analgésico

Estudos em modelos animais

• • Pomeranz B, Chiu D. Naloxone blockade of acupuncture analgesia: endorphin implicated. Life Sci. 1976 Dec 1; 19(11): 1757-62. <https://www.ncbi.nlm.nih.gov/pubmed/187888>.
  • Han JS. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci. 2003 Jan; 26(1): 17-22. <https://www.ncbi.nlm.nih.gov/pubmed/12495858>.
  • Han JS. Acupuncture and endorphins. Neurosci Lett. 2004 May 6; 361(1-3): 258-61. <https://www.ncbi.nlm.nih.gov/pubmed/15135942>.
  • Goldman N et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci. 2010 Jul; 13(7): 883-8. <https://www.ncbi.nlm.nih.gov/pubmed/20512135>.
  • Yi M et al. Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro-acupuncture in the formalin-induced inflammatory pain model of rats. Mol Pain. 2011 Aug 22;7:61. <https://pubmed.ncbi.nlm.nih.gov/21854647/>.
  • Jang JH et al. Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex. Pain . 2021 Feb 1;162(2):514-530. <https://pubmed.ncbi.nlm.nih.gov/32796318/>.
  • Shi JT, Cao WY, Zhang XN, Wan HY, Su YS, Qu ZY, Wang R, He W, Jing XH, Wang XY. Local analgesia of electroacupuncture is mediated by the recruitment of neutrophils and released β-endorphins. Pain. 2023 Apr 7. <https://pubmed.ncbi.nlm.nih.gov/37027145/>.

Estudos em humanos

• • Ishimaru K et al. Analgesic effects induced by TENS and electroacupuncture with different types of stimulating electrodes on deep tissues in human subjects. Pain. 1995 Nov; 63(2): 181-7. <https://www.ncbi.nlm.nih.gov/pubmed/8628583>.
  • Hui KK et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp. 2000; 9(1): 13-25.<https://www.ncbi.nlm.nih.gov/pubmed/10643726>.
  • Napadow V et al. Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum Brain Mapp. 2005 Mar;24(3):193-205. <https://www.ncbi.nlm.nih.gov/pubmed/15499576>.
  • Napadow V et al. Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture. Hum Brain Mapp. 2007 Mar; 28(3): 159-71. <https://www.ncbi.nlm.nih.gov/pubmed/16761270>.
  • Napadow V et al. Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture. Neuroimage. 2009 Aug 1;47(1):289-301. <https://pubmed.ncbi.nlm.nih.gov/19345268/>.
  • Harris RE et al. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage. 2009 Sep;47(3):1077-85. <https://pubmed.ncbi.nlm.nih.gov/19501658/>.
  • Chae Y et al. The neural substrates of verum acupuncture compared to non-penetrating placebo needle: an fMRI study. Neurosci Lett. 2009 Jan 30;450(2):80-4. <https://www.ncbi.nlm.nih.gov/pubmed/19061937>.
  • Li C et al. Prolonged repeated acupuncture stimulation induces habituation effects in pain-related brain areas: an FMRI study. PLoS One. 2014 May 12;9(5):e97502. <https://pubmed.ncbi.nlm.nih.gov/24821143/>.
  • Lin YJ et al. Effect of acupuncture ‘dose’ on modulation of the default mode network of the brain. Acupunct Med.  2016 Dec;34(6):425-432. <https://pubmed.ncbi.nlm.nih.gov/27841974/>.
  • Zhang S et al. Different mechanisms of contralateral- or ipsilateral-acupuncture to modulate the brain activity in patients with unilateral chronic shoulder pain: a pilot fMRI study. J Pain Res. 2018 Mar 7;11:505-514. <https://pubmed.ncbi.nlm.nih.gov/29563830/>.
  • Yu S, Ortiz A, Gollub RL, Wilson G, Gerber J, Park J, Huang Y, Shen W, Chan ST, Wasan AD, Edwards RR, Napadow V, Kaptchuk TJ, Rosen B, Kong J. Acupuncture Treatment Modulates the Connectivity of Key Regions of the Descending Pain Modulation and Reward Systems in Patients with Chronic Low Back Pain. J Clin Med. 2020 Jun 3;9(6):1719. <https://pubmed.ncbi.nlm.nih.gov/32503194/>.
  • Brito FX et al. Electroacupuncture modulates cortical excitability in a manner dependent on the parameters used. Acupunct Med. 2021 Dec 9;9645284211057560. <https://pubmed.ncbi.nlm.nih.gov/34886714/>.

Síntese dos mecanismos e lacunas

• • Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol. 2008 Aug;85(4):355-75. <https://pubmed.ncbi.nlm.nih.gov/18582529/>.
  • Han JS et al. Acupuncture analgesia: areas of consensus and controversy. Pain. 2011 Mar; 152(3 Suppl): S41-8. <https://www.ncbi.nlm.nih.gov/pubmed/21078546>.
  • Zhang R et al. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology. 2014 Feb;120(2):482-503. <https://pubmed.ncbi.nlm.nih.gov/24322588/>.

Efeito anti-inflamatório

• Zijlstra FJ et al. Anti-inflammatory actions of acupuncture. Mediators Inflamm. 2003 Apr; 12(2): 59-69. <https://www.ncbi.nlm.nih.gov/pubmed/12775355>.
• Torres-Rosas et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med. 2014 Mar;20(3):291-5. <https://pubmed.ncbi.nlm.nih.gov/24562381/>.
• Morgana D. da Silva et al. IL-10 Cytokine Released from M2 Macrophages Is Crucial for Analgesic and Anti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain. Mol Neurobiol. 2015 Feb; 51(1): 19–31. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276737/>.
• Liu S et al. A neuroanatomical basis for electroacupuncture to drive the vagal–adrenal axis. Nature. 2021 Oct 13. <https://pubmed.ncbi.nlm.nih.gov/34646018/>.

Efeito biomecânico

• Langevin HM et al. Biomechanical response to acupuncture needling in humans. J Appl Physiol (1985). 2001 Dec;91(6):2471-8. <https://pubmed.ncbi.nlm.nih.gov/11717207/>.
• Langevin HM et al. Evidence of connective tissue involvement in acupuncture. FASEB J. 2002 Jun; 16(8): 872-4. Epub 2002 Apr 10. <https://www.ncbi.nlm.nih.gov/pubmed/11967233>.
• Langevin et al. Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture. FASEB J. 2001 Oct;15(12):2275-82. <https://pubmed.ncbi.nlm.nih.gov/11641255/>.
• Langevin HM, Yandow JA. Relationship of Acupuncture Points and Meridians to Connective Tissue Planes. Anat Rec. 2002 Dec 15;269(6):257-65. <https://pubmed.ncbi.nlm.nih.gov/12467083/?from_term=acupuncture&from_pos=8>.

Acupontos

Hipersensibilidade álgica do acuponto

• Yang E, Lu W, Muñoz-Vergara D, Goldfinger E, Kaptchuk TJ, Napadow V, Ahn AC, Wayne PM. Acupoint Sensitivity in Health and Disease: A Systematic Review. J Integr Complement Med. 2024 May 16. <https://pubmed.ncbi.nlm.nih.gov/38748400/>.
• Tan H et al. Acupoints sensitization in people with and without chronic low back pain: A matched-sample cross-sectional study. J Back Musculoskelet Rehabil. 2023;36(1):137-146. <https://pubmed.ncbi.nlm.nih.gov/35871318/>.
• Zhang M et al. Acupoint Sensitization is Associated with Increased Excitability and Hyperpolarization-Activated Current (I h) in C- But Not Aδ-Type Neurons. Neuroscience. 2019 Apr 15;404:499-509. <https://pubmed.ncbi.nlm.nih.gov/30826524/>.
• Tan H et al. Understanding Acupoint Sensitization: A Narrative Review on Phenomena, Potential Mechanism, and Clinical Application. Evid Based Complement Alternat Med. 2019; 2019: 6064358. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710800/>.
• Kim DH et al. Acupuncture points can be identified as cutaneous neurogenic inflammatory spots. Sci Rep. 2017 Nov 9;7(1):15214. <https://pubmed.ncbi.nlm.nih.gov/29123119/>.
• Yan CQ et al. Detection of peripheral and central sensitisation at acupoints in patients with unilateral shoulder pain in Beijing: a cross-sectional matched case-control study. BMJ Open. 2017 Jun 15;7(6):e014438. <https://pubmed.ncbi.nlm.nih.gov/28619769/>.

Características anatômicas e elétricas dos acupontos

• Lee M et al. Distinct Neuroanatomical Structures of Acupoints Kidney 1 to Kidney 8: A Cadaveric Study. Med Acupunct. 2019 Feb 1;31(1):19-28. <https://pubmed.ncbi.nlm.nih.gov/30805076/>.
• Ahn AC et al. Electrical impedance of acupuncture meridians: the relevance of subcutaneous collagenous bands. PLoS One. 2010 Jul 30;5(7):e11907. <https://pubmed.ncbi.nlm.nih.gov/20689594/>.

Auriculoterapia

Inervação auricular

• Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. <https://www.ncbi.nlm.nih.gov/pubmed/11835542/>.
• Butt MF et al. The Anatomical Basis for Transcutaneous Auricular Vagus Nerve Stimulation. J Anat. 2020 Apr;236(4):588-611. <https://pubmed.ncbi.nlm.nih.gov/31742681/?from_term=Ear+acupuncture+and+fMRI&from_sort=date&from_pos=1>.

Efeito anti-inflamatório

• Yeh CH et al. Biological Correlates of the Effects of Auricular Point Acupressure on Pain. Pain Manag Nurs. 2023 Feb;24(1):19-26. <https://pubmed.ncbi.nlm.nih.gov/36543665/>.
• Liu CH et al. Neural Networks and the Anti-Inflammatory Effect of Transcutaneous Auricular Vagus Nerve Stimulation in Depression. J Neuroinflammation. 2020 Feb 12;17(1):54. <https://pubmed.ncbi.nlm.nih.gov/32050990/>.
• Zhao YX et al. Transcutaneous Auricular Vagus Nerve Stimulation Protects Endotoxemic Rat From Lipopolysaccharide-Induced Inflammation. Evid Based Complement Alternat Med. 2012;2012:627023. <https://pubmed.ncbi.nlm.nih.gov/23346208/>.
• Chung WY et al. Peripheral muscarinic receptors mediate the anti-inflammatory effects of auricular acupuncture. Chin Med. 2011 Jan 21;6(1):3. <https://www.ncbi.nlm.nih.gov/pubmed/21251313>.

Efeito analgésico

• Abbate D et al. beta-Endorphin and electroacupuncture. Lancet. 1980 Dec 13;2(8207):1309. <https://pubmed.ncbi.nlm.nih.gov/6108484/>.
• Usichenko T et al. Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture. Brain Stimul. 2017 Nov – Dec;10(6):1042-1044. <https://www.ncbi.nlm.nih.gov/pubmed/28803834>.
• Mercante B et al. Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves. Medicines (Basel). 2018 Jan 21;5(1). <https://www.ncbi.nlm.nih.gov/pubmed/29361732>.
• Zhang Y et al. Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: An fMRI study. Neuroimage Clin. 2019;24:101971. <https://pubmed.ncbi.nlm.nih.gov/31648171/>.
• Neves ML et al. The antinociceptive effect of manual acupuncture in the auricular branch of the vagus nerve in visceral and somatic acute pain models and its laterality dependence. Life Sci. 2022 Sep 26;121000. <https://pubmed.ncbi.nlm.nih.gov/36174710/>.

Especificidade do acuponto

• Romoli M et al. Ear Acupuncture and fMRI: A Pilot Study for Assessing the Specificity of Auricular Points. Neurol Sci. 2014 May;35 Suppl 1:189-93. <https://pubmed.ncbi.nlm.nih.gov/24867864/?from_term=Ear+acupuncture+and+fMRI&from_sort=date&from_pos=6>.
• Wang SJ et al. Acupoint specificity on acupuncture regulation of hypothalamic- pituitary-adrenal cortex axis function. BMC Complement Altern Med. 2015 Mar 27;15:87. <https://pubmed.ncbi.nlm.nih.gov/25887143/>.
• Li F et al. What is the Acupoint? A preliminary review of Acupoints. Pain Med. 2015 Oct;16(10):1905-15. <https://pubmed.ncbi.nlm.nih.gov/25975413/>.
• Szopiński  JZ, Mngomezulu V. Influence of Internal Organ Pathology on Vascular Permeability of Related Skin Zones: An Attempt to Visualize Organ Projection Areas. Med Acupunct. 2017 Oct 1;29(5):300-307. <https://pubmed.ncbi.nlm.nih.gov/29067140/?from_term=Ear+acupuncture+and+fMRI&from_sort=date&from_pos=3>.
• Peng L et al. Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI. Hear Res. 2018 Mar;359:1-12. <https://www.ncbi.nlm.nih.gov/pubmed/29305037>.

Impedância no acuponto

• Szopinski JZ et al. Influence of organ pathology on the electrical parameters in organ projection areas of the skin. J Tradit Chin Med. 2006 Sep;26(3):218-25. <https://pubmed.ncbi.nlm.nih.gov/17078457/#:~:text=Pathology%20of%20an%20internal%20organ%20causes%20significant%20rectification,of%20the%20diseased%20organ%27s%20projection%20areas%20is%20increased>.
• Szopiński JZ, Mngomezulu V. Influence of Internal Organ Pathology on Vascular Permeability of Related Skin Zones: An Attempt to Visualize Organ Projection Areas. Med Acupunct. 2017 Oct 1;29(5):300-307. <https://pubmed.ncbi.nlm.nih.gov/29067140/>.

Terapias Mente-Corpo

• Zhang X, Zong B, Zhao W, Li L. Effects of Mind-Body Exercise on Brain Structure and Function: A Systematic Review on MRI Studies. Brain Sci. 2021 Feb 7;11(2):205. <https://pubmed.ncbi.nlm.nih.gov/33562412/>.
• Bower JE, Irwin MR. Mind-body Therapies and Control of Inflammatory Biology: A Descriptive Review. Brain Behav Immun. 2016 Jan;51:1-11. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679419/>.
• Chin MS, Kales SN. Understanding Mind-Body Disciplines: A Pilot Study of Paced Breathing and Dynamic Muscle Contraction on Autonomic Nervous System Reactivity. Stress Health. 2019 Oct;35(4):542-548. <https://pubmed.ncbi.nlm.nih.gov/31347763/?from_term=qigong+AND+mechanisms+&from_sort=date&from_pos=8>.
• Chen X et al. Dao Yin (a.k.a. Qigong): Origin, Development, Potential Mechanisms, and Clinical Applications. Evid Based Complement Alternat Med. 2019; 2019: 3705120. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854271/>.
• Klein P et al. Meditative Movement, Energetic, and Physical Analyses of Three Qigong Exercises: Unification of Eastern and Western Mechanistic Exercise Theory. Medicines (Basel). 2017 Sep 23;4(4):69. <https://pubmed.ncbi.nlm.nih.gov/28946612/?from_term=qigong+AND+mechanisms&from_sort=date&from_page=3&from_pos=2>.

PICS

• Chen L, Michalsen A. Management of chronic pain using complementary and integrative medicine. BMJ. 2017 Apr 24;357:j1284. doi: 10.1136/bmj.j1284. <https://www.ncbi.nlm.nih.gov/pubmed/28438745>.
• Oke SL, Tracey KJ. The inflammatory reflex and the role of complementary and alternative medical therapies. Ann N Y Acad Sci. 2009 Aug;1172:172-80. <https://www.ncbi.nlm.nih.gov/pubmed/19743552>.
• Wang M et al. Mechanism of Traditional Chinese Medicine in Treating Knee Osteoarthritis. J Pain Res. 2020 Jun 15;13:1421-1429. <https://pubmed.ncbi.nlm.nih.gov/32606908/>.
• Zhang Q et al. Mechanisms of acupuncture-electroacupuncture on inflammatory pain. Mol Pain. 2023 Jan-Dec;19:17448069231202882. <https://pubmed.ncbi.nlm.nih.gov/37678839/>.
• Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med. 2002 Mar 5;136(5):374-83. <https://pubmed.ncbi.nlm.nih.gov/11874310/>.
• A Vickers, C Zollman. ABC of complementary medicine. Acupuncture. BMJ. 1999 Oct 9;319(7215):973-6. <https://pubmed.ncbi.nlm.nih.gov/10514163/>.