Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives

Journal of Complementary Therapies in Health ISSN 2975-9323 |eISSN 2975-9552 Journal of Complementary Therapies in Health 2025:3(3). doi:10.5281/zenodo.17257459 institutoptc.com/journal-complementary-therapies Review Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives. Jorge André Matos1, Cátia Relvas1*, Marina Silva1, and Daniel Sebastião1. 1 ABS – Health Level, Atlântico Business School, Vila Nova de Gaia, Porto, Portugal. * Correspondence: catiarelvas[email protected] Abstract Chronic pain affects 42% of the Portuguese population, with a high socioeconomic impact. Traditional Chinese Medicine (TCM) offers promising therapies, such as acupuncture, electroacupuncture, herbal medicine, mind-body exercises (Tai Chi, Qigong), Tui Na massage, and moxibustion. This literature review aims to critically analyse the neurophysiological mechanisms and scientific evidence of these interventions in pain control. It concludes that these therapies modulate key neuroimmunological pathways. Acupuncture activates endogenous analgesia (β-endorphins) and suppresses inflammation via TLR2/NF-κB. Phytotherapy blocks pain receptors and inhibits glial activation. Qigong, as a mind-body exercise, regulates the stress axis (cortisol). In addition, moxibustion improves circulation and reduces neuropathic pain. The integration of these approaches offers an effective multidimensional strategy, supported by current evidence, although standardized, randomized clinical trials with large samples from different populations are still needed. Keywords: Traditional Chinese Medicine; Pain Management; Acupuncture Mechanisms; Herbal Medicine; Qigong; Neuroimmunology; Chronic Pain. 1. Introduction Chronic pain is a global public health problem, affecting more than 40% of the Portuguese population and generating significant socioeconomic costs 1,2. In Portugal, 70% of emergency cases are related to acute pain, whose poor management fosters chronification 3,4 while chronic pain affects more than 30% of adults, often associated with musculoskeletal disorders 5. Chronic pain involves central sensitization and neuroimmunological dysregulation. Peripheral nociceptors activate ascending pathways to the cortex, triggering a process of persistent inflammation that lowers neuronal thresholds and amplifies pain perception. Effective control of this dysregulation requires strategies that act on these mechanisms, such as TCM therapies. Pain is the most frequent symptom associated with disease, and it is the responsibility of healthcare professionals to identify its origin, relieve suffering, and restore functionality 6. According to the Portuguese Directorate-General of Health 7, acute pain is an important indicator of injury or physiological dysfunction and a common reason for seeking care. It represents a multifaceted sensory and emotional experience, resulting from injury, disease, or other medical conditions, whose treatment aims to improve quality of life and optimize daily performance 8. Pain control should be a priority in healthcare, integrating the humanization of services. The transition from acute to chronic pain involves complex pathophysiological Citation: Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives. Journal of Complementary Therapies in Health. 2025;3(3) 10.5281/zenodo.17257459 Academic Editor: Jorge Rodrigues Received: 15 September 2025 Reviewed: 28 September 2025 Revised: 2 October 2025 Accepted: 2 October 2025 Published: 3 October 2025 Publisher’s Note: IPTC stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: ©2025 by the authors. Submitted for open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Journal of Complementary Therapies in Health 2025: 3(3). 2 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 mechanisms, including activation of peripheral nociceptors, transmission to the central nervous system, neuronal activation in the thalamus and cortex, and peripheral and central sensitization, all of which amplify pain perception 9. The lowering of neuronal activation thresholds and the expansion of the sensitive area contribute to the chronification of pain. TCM, aligned with national guidelines 7,10, addresses pain as a multidimensional experience (sensory, emotional, psychological, social, and cultural). TCM employs techniques such as acupuncture and electroacupuncture (integrated into national protocols for neuropathic pain) to restore functional balance through modulation of neural pathways and endorphin release 11,12. This review analyses the pathophysiological mechanisms and the effectiveness of these therapies, aiming to support their clinical application in broader scenarios. 2. Methodology This narrative review aims to critically analyse some neurophysiological mechanisms and the scientific evidence regarding TCM therapeutic interventions in pain management. A bibliographic search was conducted in PubMed, SciELO, ScienceDirect, and Google Scholar (up to August 2025), using the keywords: “Traditional Chinese Medicine”, “pain management”, “acupuncture mechanisms”, “herbal medicine”, “qigong”, “neuroimmunology”, and “chronic pain”, with the purpose of selecting relevant articles to address our research question: What are the mechanisms of action of TCM in pain management according to current scientific evidence? Inclusion criteria were defined as randomized clinical trials (RCTs), systematic reviews, and meta-analyses published in Portuguese and English, without temporal restriction, but giving preference, whenever possible, to studies published in the last three years. Exclusion criteria included studies written in other languages not covered by the inclusion criteria, texts not available in full, or irrelevant for answering the research question. Data were thematically organized by intervention: acupuncture, herbal medicine, Tui Na massage, moxibustion, Qigong, and Tai Chi, with assessment of mechanisms of physiological action, clinical efficacy, and respective limitations 3. Results 3.1. Acupuncture The most recognized mechanisms of action of acupuncture, in light of current evidence, include activation of Aδ/C fibres and the release of β-endorphins and descending modulation of μ-opioid receptor pathways 2,11. This process triggers functional reorganization of the central nervous system, including brain reward networks 13 Although TCM relies on diagnostic methods that enable personalized treatment plans for each patient, several acupuncture point protocols are recurrently used in experimental settings to establish evidence-based clinical approaches. Manual or electrostimulation of points LI4, LR3, ST36, PC6, and SP6 has shown positive results in reducing musculoskeletal pain in older adults after four sessions of treatment 11 (Table 1). In oncological pain, the combination of acupuncture with analgesics increases therapeutic efficacy and reduces adverse effects 14. Acupuncture enhances cancer pain management through synergistic mechanisms: by stimulating the release of endogenous opioids (endorphins and encephalin) in the central nervous system (which act on the same receptors [μ, δ, κ] as exogenous opioids such as morphine) it amplifies pharmacological analgesia. Simultaneously, it modulates the inflammatory response by reducing pro-inflammatory cytokines (TNF-α, IL-6) associated with tumour pain and neuroinflammation. In cases of neuropathic pain, frequent in metastases, acupuncture normalizes neuronal hyperexcitability in the somatosensory cortex and thalamus, inhibiting central sensitization. It also regulates the hypothalamic–pituitary–adrenal (HPA) axis and increases serotonin Journal of Complementary Therapies in Health 2025: 3(3). 3 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 levels, thereby attenuating anxiety, depression, and the affective dimension of pain, promoting a more effective multidimensional approach. Some reviewed studies innovated by developing and testing mathematical models 15,16 for designing individualized yet scientifically reproducible protocols. These models use complex equations grounded in basic TCM theories such as Yin–Yang Theory (dynamic energetic homeostasis), the chronobiology of Zang Fu (integrated organ systems), and the latest knowledge of microsystems that anatomically reflect pain by somatotopy. The model is based on integrated neurophysiological mechanisms, where individualized acupoint selection activates pain modulation pathways through three main axes: (1) stimulation of myelinated Aβ nerve fibres, which inhibit nociceptive transmission at the dorsal horn of the spinal cord via Gate Control Theory, blocking unmyelinated C-fibre signals; (2) activation of descending neuroimmunological networks, including release of endogenous opioids (β-endorphin, dynorphin) and suppression of pro-inflammatory cytokines (TNF-α, IL-6) through the HPA axis; and (3) normalization of functional brain connectivity, demonstrated in several studies by functional magnetic resonance imaging (fMRI) 17,18, rebalancing default mode networks (DMN) and hyperexcitable somatosensory areas, thereby reversing central sensitization. These mechanisms are mathematically quantified through algorithms that integrate variables such as anatomical pain location, circadian rhythms, and inflammatory biomarkers, transforming empirical principles of Chinese Medicine into reproducible protocols with integrated analgesic action. The synergy between neuroimaging, immunology, and mathematics validates acupuncture as a systemic neuromodulation therapy, where anatomical precision of points produces clinically measurable and reproducible effects. 3.2. Electroacupuncture Electroacupuncture enhances the analgesic effects of traditional acupuncture through two fundamental neuroimmunological mechanisms. It suppresses the TLR2/NFκB signalling pathway, significantly reducing the production of pro-inflammatory cytokines such as TNF-α and IL-6 19-21 (Figure 2). It also promotes neutrophil recruitment and local release of endogenous opioids, particularly β-endorphins, thereby strengthening peripheral analgesia 20. Clinically, the technique demonstrates robust efficacy, with studies reporting a 30–45% reduction in the use of conventional analgesics in patients with inflammatory or neuropathic pain (Table 1). Figure 1. Neuroimmunological pathways of Acupuncture/Electroacupuncture. Journal of Complementary Therapies in Health 2025: 3(3). 4 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 It stands out for its superiority in specific conditions: in peripheral neuropathic pain, meta-analyses confirm greater efficacy compared with NSAIDs, with significant reductions in oedema and hyperalgesia; in rheumatoid arthritis, it is associated with decreased inflammatory markers (such as C-reactive protein) and improved joint mobility 19. Additionally, electroacupuncture shows excellent cost-effectiveness, with lower long-term complication costs compared to conventional pharmacological therapies 22. In Portuguese clinical contexts, the technique is applied through optimized protocols combining classical points (such as ST36 and LI11) with specific stimulation frequencies (2–100 Hz) to maximize neuroimmunological modulation. It is integrated into national pain units, particularly for reducing opioid use in cancer patients with neuropathic pain, in alignment with the guidelines of the National Program for Pain Control 12. Figure 2. Mechanism of TLR2/NF-κB Pathway Inhibition by Electroacupuncture. Despite its benefits, limitations remain, notably the methodological heterogeneity in neuropathic pain studies, which requires future standardization of parameters such as stimulation intensity and duration. 3.3. Herbal Medicine Herbal medicine in TCM acts through specific neuropharmacological mechanisms. Alkaloids such as tetrahydropalmatine (Corydalis yanhusuo) block dopaminergic and opioid receptors while simultaneously inhibiting glial activation associated with neuroinflammation 23 (Figure 3). Other compounds, such as derivatives of Sinomenium acutum, modulate ion channels and suppress key inflammatory pathways, including cyclooxygenase-2 (COX-2) inhibition and the nuclear factor kappa B (NF-κB) pathway, thereby reducing the production of prostaglandins and pro-inflammatory cytokines (e.g., TNF-α, IL1β). Journal of Complementary Therapies in Health 2025: 3(3). 5 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 Table 1. Clinical Studies on Acupuncture and Evidence for Electroacupuncture. Ref. Study Objective Intervention / Protocol Main Results 13 Evaluate central effects of acupuncture Protocol not specified; functional analysis of CNS Functional changes in the CNS; reorganization of neural functions associated with emotions and pain perception 14 Compare acupuncture + pharmacological analgesia vs. medication alone in cancer pain LI4, LR3, ST36, PC6, SP6 + analgesic therapy Higher relief rate; lower pain intensity; fewer adverse effects; faster onset; longer duration of effect 15 Develop and apply a mathematical model for individualized point selection Yin–Yang balance, “Chinese clock,” angular combinations, somatotopy, ashi points Methodological proposal for rational point selection; foundation for individualized and replicable protocols 16 Apply a mathematical model of individualized acupuncture in unilateral musculoskeletal pain Structured protocol integrating “Chinese clock,” somatotopy/mirror correspondence, identification of ashi points; systemic and indwelling needles; channel selection by angular calculations; intra-session adjustment guided by VAS In 5 clinical cases, immediate and sustained pain reduction; VAS 0 in 4/5 cases; systematized, replicable protocol compatible with clinical individualization; need for validation in larger samples 19 Evaluate effects of electroacupuncture on CFA-induced inflammatory pain Electroacupuncture at specific points; low-intensity stimulation Attenuation of inflammatory pain via regulation of CaMKII protein 21 Investigate the role of the TLR2 receptor in electroacupuncture-induced analgesia in inflammatory pain Electroacupuncture in an animal model of inflammatory pain Modulation of the TLR2 pathway; reduction of pro-inflammatory cytokine production; pain relief 20 Evaluate peripheral mechanisms of electroacupuncture in inflammation Local application of electroacupuncture at inflamed area Neutrophil recruitment; increase in β-endorphins; local analgesia 22 Evaluate economic impact of electroacupuncture in chronic pain Electroacupuncture in patients with vertebral syndrome with irradiation Multimodal analgesia reducing NSAIDs, via endogenous opioids, adenosine, serotonin, GABA, and modulation Figure 3. Anti-inflammatory Mechanisms of Corydalis and Sinomenium. Journal of Complementary Therapies in Health 2025: 3(3). 6 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 Clinically, herbal compresses have been shown to significantly reduce pain intensity and inflammatory markers (such as C-reactive protein) in tissue injuries 24 (Table 2). However, application requires specialized supervision due to the risk of pharmacological interactions, particularly with anticoagulants or immunosuppressants 25. This phytotherapeutic approach offers a targeted analgesic alternative, although the standardization of formulations, monitoring of adverse effects, and especially the potential for interaction with other therapies remain operational challenges. 3.4. Mind–Body Exercises Qigong Qigong acts through vegetative biofeedback 26-29, regulating the hypothalamic–pituitary–adrenal (HPA) axis and reducing cortisol and interleukin-6 (IL-6) levels 30. Its clinical efficacy is demonstrated when practiced at least three times per week under specialised supervision (Table 2). Tai Chi This practice combines movement and meditation, promoting improvements in mobility, balance, and psychological well-being 29,31-33. Although its benefits are proven in cases of osteoarthritis, scientific evidence remains limited for the treatment of chronic low back pain (Table 2). 3.5. Tui Na massage Tui Na massage employs manual pressure and friction techniques acting directly on myofascial trigger points and meridians, improving blood circulation and reducing Qi stagnation 34. Preliminary studies demonstrate its efficacy in managing chronic low back pain associated with anxiety 35 (Table 2), although evidence still requires consolidation through more robust clinical trials. 3.6. Moxibustion Moxibustion uses the combustion of Artemisia vulgaris to stimulate specific points, promoting increased blood circulation and modulation of inflammatory processes. According to meta-analyses, it demonstrates comparative superiority over NSAIDs in the treatment of peripheral neuropathic pain, although this conclusion is limited by methodological heterogeneity of the studies analysed 36 (Table 2). 4. Discussion 4.1. Neuroimmunological Synthesis TCM therapies modulate the neuroimmune axis through complementary mechanisms, with practical effects validated by evidence. Electroacupuncture primarily acts on suppression of the TLR2/NF-κB pathway, inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-6) and reducing oedema in conditions such as arthritis 20,21,36. This mechanism, combined with neutrophil recruitment and local β-endorphin release, allows a 30–45% reduction in the use of conventional analgesics, positioning it as a cost-effective alternative to pharmacotherapy in neuropathic pain 22. Herbal medicine focuses on modulation of μ-opioid receptors through alkaloids such as tetrahydropalmatine (Corydalis yanhusuo), offering analgesia without the risk of respiratory depression, a critical advantage over synthetic opioids 23. Herbal compresses have shown reductions in inflammatory markers (e.g., C-reactive protein) in tissue injuries 24, though they require specialized supervision to prevent drug–herb interactions 23. Journal of Complementary Therapies in Health 2025: 3(3). 7 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 Qigong and Tai Chi regulate the HPA axis, lowering cortisol and IL-6 levels, which translates into reduced stress markers and improved psychological well-being 29-33. Practiced at least three times per week under guidance, they show consolidated efficacy in osteoarthritis, although evidence for chronic low back pain remains limited 32,33. Table 2. Summary of mechanisms of action and evidence for non-invasive therapies (Herbal Medicine, Qigong, Tai Chi, Tui Na, Moxibustion). Ref. Study Objective Intervention / Protocol Main Results 23 Review analgesic alkaloids derived from TCM in pain management Review of compounds (tetrahydropalmatine – Corydalis yanhusuo; sinomenine – Sinomenium acutum; ligustrazine – Ligusticum chuanxiong; lappaconitine – Aconitum carmichaelii; gelsemine – Gelsemium elegans) Mechanisms: dopaminergic/opioid receptors, inhibition of glial activation, modulation of ion channels and neurotransmitters; potential for acute and chronic pain 24 Evaluate TCM herbal compresses in pain and inflammation Adhesive with: Common monkshood root (15 g), Achyranthes bidentata (15 g), bitter orange (15 g), garden balsam stem (15 g), safflower (10 g), ground beetle (10 g), ginger (10 g), Haichow Elsholtzia herb (10 g) Pain reduction; decreased inflammatory cytokines; improved quality of life in soft tissue injuries 25 Describe the use of plant-based analgesics in pain-related diseases and alert to risks Highlighting: Harpagophytum procumbens (devil’s claw), Curcuma longa (turmeric), Zingiber officinale (ginger) Widespread use; potential benefits as adjunct; possibility of adverse effects and drug–herb interactions; need for professional monitoring 30 Review evidence on internal Qigong in painful conditions Systematic review of clinical trials (practice of internal Qigong) Indications of pain reduction in various conditions; methodological quality variable, more robust RCTs needed 31 Assess the influence of Qigong on chronic pain Systematic review of clinical studies Effective in pain relief when practiced correctly and regularly, ideally under supervision 33 Describe the application of Tai Chi in chronic pain management Narrative review; description of physiological mechanisms and clinical benefits Evidence of improvement in pain, physical function, balance, and overall well-being in various chronic pain conditions 32 Review and analyse RCT evidence on Tai Chi in chronic painful conditions Systematic review and meta-analysis of RCTs; different Tai Chi protocols Significant reduction in pain and improvement in physical function; heterogeneity in protocols 35 Analyse trends and evidence on Tui Na in the treatment of chronic pain Bibliometric analysis and literature review Growing evidence of effectiveness; emphasis on potential in musculoskeletal pain; need for more high-quality RCTs 36 Evaluate effectiveness and costeffectiveness of acupuncture and moxibustion in peripheral neuropathic pain Network meta-analysis simultaneously comparing multiple interventions based on classical probability and cost-effectiveness assessment Moxibustion showed potential in reducing peripheral neuropathic pain, sometimes with results superior to NSAIDs, but evidence is of variable quality and requires more robust RCTs 4.2. Clinical Synergy and Relevance The convergence of mechanisms of action across these therapies, namely anti-inflammatory suppression (electroacupuncture), safe opioid modulation (herbal medicine), and neuroendocrine regulation (Qigong/Tai Chi), targets the multiple dimensions of chronic pain: Journal of Complementary Therapies in Health 2025: 3(3). 8 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 • Central sensitization, reversed by normalization of brain connectivity (fMRI studies) 17,18; • Inflammatory cascades, inhibited at the molecular level 21,23; • Emotional components, attenuated by HPA axis regulation and serotonin increase 14,15,30. This multidimensional approach, aligned with the Portuguese National Program for Pain Control 7,12, provides an integrative care strategy to improve quality of life in patients with chronic pain while maintaining economic sustainability. Despite advances, critical challenges persist: the definition of a national strategy to minimize side effects from interactions (through guideline creation), protocol standardization, and validation in diverse populations are essential to strengthen scientific reproducibility 36. The integration of these therapies into multidisciplinary care models, aligned with the guidelines of the Portuguese National Program for Pain Control, represents a promising and scientifically validated path toward inclusion in public health policies. This patient-centred approach combines clinical efficiency (30–45% reduction in analgesic use), economic sustainability (cost-effectiveness compared with pharmacotherapies), and a favourable safety profile, minimizing adverse effects and enhancing integrative responses in managing chronic pain in Portugal. 5. Conclusion TCM is consolidating as a valid and scientifically grounded therapeutic resource for chronic pain management, supported by demonstrable neuroimmunological mechanisms. Through acupuncture and electroacupuncture, inflammatory pathways are modulated and endogenous analgesia is enhanced, reducing dependence on conventional drugs. Herbal medicine provides bioactive compounds with specific actions on receptors and inflammatory cascades, offering analgesia without the systemic risks associated with synthetic opioids. Mind–body exercises (Qigong, Tai Chi) regulate stress and promote neuroendocrine homeostasis, addressing the psychosocial dimension of pain. However, full integration into the Portuguese National Health Service (SNS) requires overcoming challenges such as protocol standardization and comprehensive training of healthcare professionals regarding risks of herbal medicine interactions. Another aspect to consider is the need for robust RCTs in Western populations. Credit author statement: Conceptualisation, J.A.M., Methodology, J.A.M. and C.R.; Software, M.S.; Validation, C.R.; Formal analysis, J.A.M., M.S., D.S., and C.R.; Investigation, J.A.M., M.S., D.S., and C.R.; Resources, M.S. and D.S., Data Curation, , J.A.M. and C.R.; Writing - Original Draft, J.A.M., M.S., D.S., and C.R.; Writing - Review & Editing, M.S., J.A.M., and C.R.; Visualization, M.S., D.S., J.A.M., and C.R.; Supervision, D.S.; Project administration, J.A.M. All authors have read and agreed to the published version of the manuscript. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of Interest: The authors declare that there are no conflicts of interest. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author. Journal of Complementary Therapies in Health 2025: 3(3). 9 of 10 Matos J.A., Relvas C., Silva M., Sebastião D. Integrating Traditional Chinese Medicine into Chronic Pain Care in Portugal: Neuroimmunological and Clinical Perspectives doi:10.5281/zenodo.17257459 References 1. Branco JC, Rodrigues AM, Gouveia N, Eusébio M, Ramiro S, Machado PM, et al. 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