Complementary and alternative therapies are interventions that are not considered part of the conventional medical system, but are used to complement or replace it. Complementary and alternative therapies encompass various techniques that may relieve chronic pain through modulating physiological and psychological factors. Some of the promising options include acupuncture, yoga, tai chi, exercise, and music therapy.
Acupuncture
Acupuncture refers to stimulation of traditional Chinese acupoints. While acupuncture originally involved inserting needles into the body, this section focuses specifically on non-invasive techniques, such as laser or electro-stimulation, to stimulate acupoints. Acupuncture involves stimulating traditional acupoints along meridians to modulate pain signaling. Both manual and electrical stimulation may activate Aδ and C afferent fibers, triggering release of endorphins, enkephalins, and dynorphins that bind to opioid receptors in the periphery, spinal cord, and brain to inhibit nociception [
224].
Acupuncture increases local release of adenosine, an endogenous anti-nociceptive agent, which inhibits pain transmission via adenosine A1 receptors based on biochemical assays [
225]. Functional MRI reveals acupuncture modulates limbic areas involved in affective pain dimensions and activates anti-nociceptive regions like the periaqueductal gray [
226].
Acupuncture elevates central levels of serotonin, norepinephrine, and dopamine, engaging descending inhibitory pathways according to microdialysis studies. Metabolomics analysis indicates acupuncture regulates glucose and lipid metabolism, purine metabolism, and arachidonic acid metabolism involved in anti-inflammatory effects [
227,
228].
Emerging evidence suggests acupuncture may reverse central sensitization by reducing NMDA receptor activation, neuroinflammation, and oxidative stress in the spinal cord and pain modulatory brain regions based on immunohistochemistry and polymerase chain reaction (PCR) studies [
229].
Clinical studies demonstrate the analgesic effects of acupuncture across diverse chronic pain conditions. Beyond low back pain and knee osteoarthritis, clinical trials show acupuncture analgesic effects in cancer-related pain, dysmenorrhea, migraine, tension headaches, abdominal pain, and chemotherapy-induced peripheral neuropathy, potentially by modulating sensory, affective, and cognitive pain dimensions [
230‐
237] (Additional file
1: Fig. S3).
Importantly, research shows acupuncture enhances chronic pain relief when combined with pharmacological and non-pharmacological therapies. For example, acupuncture plus morphine demonstrates greater analgesic effects and fewer side effects than morphine alone for cancer pain [
238]. Acupuncture integrated into physiotherapy programs yields superior improvement in mobility and function compared to either therapy alone for knee osteoarthritis [
231]. This highlights the synergistic benefits of acupuncture through modulating multiple mechanisms when combined with other treatment modalities.
While acupuncture demonstrates potential for certain chronic pain conditions, there are limitations warranting consideration [
239]. The mechanisms underlying acupuncture analgesia remain incompletely understood. Clinical efficacy varies for different pain disorders and individuals. Sham-controlled studies reveal a large placebo component in acupuncture effects. Safety issues like infection and pneumothorax should be avoided with proper technique and single-use needles.
Moving forward, optimization of acupuncture through computational modeling, neuroimaging, and machine learning could help identify biomarkers predicting response. Integration of electrical and non-invasive laser stimulation may enhance effects while avoiding adverse events. Evidence-based guidelines are needed to inform optimal acupuncture protocols tailored to each chronic pain condition and patient. High-quality randomized controlled trials with extended follow-up should evaluate long-term analgesic effects and impact on function, side effects, and quality of life. Development of acupuncture training programs should emphasize both traditional techniques and emerging evidence [
239]. Overall, advancing acupuncture therapy through rigorous research will help unlock its potential within integrative care paradigms for chronic pain management.
Yoga and tai chi
Yoga and tai chi are mind–body practices that may relieve chronic pain and improve wellness through harmonizing physiological and psychological factors. Yoga and tai chi are ancient practices originating from India and China, respectively, which involve physical postures, movements, breathing techniques, and mental focus. They share with modern physical exercise the ability to balance key functions and cultivate optimal pain management [
240,
241].
At the molecular level, studies indicate yoga and tai chi increase anti-inflammatory cytokines like IL-10 and IL-4, while reducing pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β [
242,
243]. These effects help counteract chronic inflammatory processes underlying chronic pain conditions.
Functional MRI studies reveal yoga and tai chi can optimize abnormal functional connectivity between key pain-related brain regions. For instance, yoga normalizes altered connectivity between the default mode network and executive control network, which is associated with clinical pain severity [
244]. Tai chi improves connectivity between the basal ganglia and sensorimotor cortex, which correlates with restored motor function [
245]. Modulating dysfunctional connections in pain-related neural circuitry is crucial for translating neuroimaging findings into clinical utility.
PET imaging demonstrates yoga and tai chi increase release of endogenous opioids, serotonin, and dopamine in pain modulatory pathways including the periaqueductal gray, amygdala, and nucleus accumbens [
246]. This activates descending inhibition of nociception.
Advanced EEG signal analysis indicates yoga and tai chi alter theta, alpha, and gamma oscillations associated with sensory, cognitive, and affective processing of pain [
244]. This improves neural processing and integration of the pain experience.
Metabolomics studies show yoga and exercise induce changes in metabolites related to energy metabolism, oxidative stress, and inflammation. These biochemical effects may underlie their impact on pain [
247,
248].
Epigenetic analyses reveal yoga and tai chi facilitate chromatin remodeling and alter miRNA expression patterns related to pain and analgesia [
249]. These lasting changes may mediate long-term impact.
In addition to low back pain and osteoarthritis, emerging clinical evidence demonstrates yoga, tai chi, and physical exercise reduce pain and improve function in other chronic pain conditions, including fibromyalgia, migraine, neuropathic pain, cancer pain, multiple sclerosis pain, and inflammatory bowel disease pain [
250‐
255] (Additional file
1: Fig. S3).
For example, several randomized controlled trials show yoga provides clinically meaningful improvements in pain, fatigue, and quality of life in fibromyalgia patients [
256]. As an adjunctive therapy, yoga significantly reduces migraine headache frequency, intensity, and disability compared to pharmacotherapy alone [
257].
Exercise training alleviates cancer-related pain and chemotherapy-induced peripheral neuropathy based on multiple studies [
167]. Tai chi demonstrates significant analgesic effects in peripheral neuropathy patients, enabling reduced use of analgesics [
258].
For instance, the combination of yoga and pregabalin is more effective than either therapy alone in reducing neuropathic pain and improving sleep based on a recent randomized controlled trial. Yoga integrated into physiotherapy programs results in superior outcomes compared to individual therapies for chronic low back pain [
250]. Mindfulness meditation plus tai chi shows greater improvements in knee osteoarthritis pain and physical function versus either intervention alone [
259].
While promising, there are limitations warranting consideration, including unclear optimal protocols for different chronic pain populations, factors influencing individual variability in treatment response, and need for further research on long-term analgesic durability through high-quality longitudinal studies. Accessibility and adherence barriers should also be addressed.
Moving forward, several areas need attention to optimize clinical applications of yoga, tai chi, and exercise for chronic pain. Development of adapted protocols personalized to patient characteristics and needs through predictive algorithms and machine learning is key. Optimization of therapy delivery methods, such as VR, telerehabilitation, and mobile apps, is essential to enhance engagement [
260]. Combination strategies with emerging modalities like neurostimulation, nutraceuticals, and biologics should be explored. Large pragmatic trials on multi-component lifestyle programs integrating yoga, tai chi, and exercise are needed to inform integrative care models.
In summary, continued research on mechanisms, predictive biomarkers, delivery methods, and combination approaches will help realize the full potential of yoga, tai chi, and physical exercise as accessible, low-risk interventions that can be integrated into holistic paradigms for chronic pain management.
Music therapy
Music therapy, which employs music interventions to achieve therapeutic goals, encompasses a variety of techniques such as improvisational music therapy, song writing, music performance, and music listening. These techniques may be a promising and safe non-pharmacologic pain management option for patients with chronic pain [
261,
262].
Neuroimaging shows music therapy modulates activity and connectivity in areas like thalamus, somatosensory cortex, cingulate cortex, insula, amygdala, prefrontal cortex, and nucleus accumbens [
263]. Recent research proposes music therapy may normalize dysfunctional connectivity between default mode, salience, central executive, and reward networks that underlie sensory, affective, and cognitive dimensions of chronic pain [
264]. It may reverse maladaptive neuroplasticity and limit central sensitization.
EEG, functional MRI, and computational modeling could help predict individual pain relief response and optimize music therapy protocols. Combining music with pharmacological, physical, or psychological pain treatments may have synergistic effects through peripheral and central mechanisms.
Recent clinical trials demonstrate music therapy decreases pain in additional chronic pain conditions including low back pain, arthritis, migraine headache, chronic neck, and shoulder pain [
265‐
268] (Additional file
1: Fig. S3). Music alleviates both nociceptive and neuropathic pain through effects on sensory, cognitive, and emotional dimensions.
Integrating music therapy into physical therapy programs improves outcomes including pain relief, mobility, and quality of life versus physical therapy alone for osteoarthritis, rheumatoid arthritis, and chronic neck pain [
269]. Music optimizes physiological and psychological influences on chronic pain.
Music therapy combined with CBT enhances pain coping and reduces disability compared to either therapy alone for patients with chronic widespread pain [
270]. Music therapy optimizes multiple top-down mechanisms when combined with psychological therapies.
While music therapy demonstrates acute analgesic effects, studies evaluating its long-term efficacy in sustaining pain relief are lacking. Future research should investigate optimal music therapy protocols regarding session frequency, duration, and techniques required for maintaining benefits. Standardized measures over extended periods are needed to determine ideal regimens maximizing enduring outcomes.
Advances in neuroimaging, genetics, and machine learning techniques present opportunities to guide individualized music therapy based on a patient’s brain activity patterns, neurotransmitter function, and music preferences. Computational models could help determine optimal music parameters and predict treatment response. Personalized music selection and delivery may enhance clinical effects [
267].
Caution should be taken regarding music characteristics like tempo, rhythm, melody, and volume [
271]. Music with abruptly shifting tones or overly stimulating rhythms may exacerbate symptoms in certain chronic pain conditions. Sound levels should be carefully controlled to avoid adverse auditory effects. Overall, individualization of music therapy while considering safety factors can optimize its efficacy as a non-pharmacologic pain management approach.