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University of Texas Health Science Center at Houston Cizik School of NursingUniversity of Texas Health Science Center at Houston, McGovern Medical School
Aims: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers.
Design
This is a secondary data analysis.
Settings:
Participants/Subjects:
Methods
Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for each study group (chronic low back pain, cancer pain), between-group differences (changes in scores from pre- to post-intervention between targeted-point APA [T-APA] and non-targeted-point APA [NT-APA]), and correlations among pain intensity, interference, and biomarkers.
Results
Within-group analysis (the change score from pre- to post-APA) revealed statistically significant changes in three biomarkers: TNF-α (cancer pain in the APA group, p = .03), β-endorphin (back pain in the APA group, p = .04), and IL-2 (back pain in the NT-APA group, p = .002). Based on between-group analysis in patients with chronic low back pain (T-APA vs NT-APA), IL-4 had the largest effect size (0.35), followed by TNF-α (0.29). A strong positive monotonic relationship between IL-1β and IL-2 was detected.
Conclusions
The current findings further support the potential role of inflammatory biomarkers in the analgesic effects of APA. More work is needed to gain a comprehensive understanding of the underlying mechanisms of APA on chronic pain. Because it is simple, inexpensive, and has no negative side effects, APA can be widely disseminated as an alternative to opioids.
Comparative Effectiveness Review No. 229. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 20-EHC011.
Agency for Healthcare Research and Quality,
Rockville, MD2020
Eighteen-year trends in the prevalence of, and health care use for, noncancer pain in the United States: Data from the Medical Expenditure Panel Survey.
Sociodemographic inequalities in barriers to cancer pain management: A report from the American Cancer Society's Study of Cancer Survivors-II (SCS-II).
Substance Abuse and Mental Health Services Administration The opioid crisis and the Black/African American population: An urgent issue. Publication no. PEP20-05-02-001.
Office of Behavioral Health Equity. Substance Abuse and Mental Health Services Administration,
2020
Skelly AC, C. R., Dettori JR, Turner JA, Friedly JL, Rundell SD, Fu R, Brodt ED, Wasson N, Kantner S, Ferguson AJR. (2020). Noninvasive nonpharmacological treatment for chronic pain: A systematic review update. Comparative effectiveness review no. 227. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 20-EHC009. Retrieved October 22, 2022, from https://effectivehealthcare.ahrq.gov/products/noninvasive-nonpharm-pain-update/research.
). Even with these advances, barriers to implementing acupuncture for pain management exist, including frequent office visits, cost, and lack of access to licensed acupuncturists (
Auricular acupuncture, with origins stemming from traditional (body) acupuncture, is a unique “microsystem” that uses only ear points for treatment. Compared to body acupuncture, it is easier to learn and administer. Paul Nogier, a French neurologist and physician (
) described a somatotopic representation of the human body on the ears. As part of the system of diagnosis, the presence of active areas on the ear meriting treatment is confirmed by examination of the electrodermal response, via the use of a point finder (
National Acupuncture Detoxification Association. (2010). Training resource manual: A handbook for individuals training in the National Acupuncture Detoxification Association's Five-needle Acudetox Protocol (4th ed.).
. The Defense and Veterans Center for Integrative Pain Management and Veterans Health Administration National Pain Management Program have offered battlefield auricular acupuncture training courses for non-acupuncturists to enhance their pain management skills (
Building capacity for complementary and integrative medicine through a large, cross-agency, acupuncture training program: Lessons learned from a military health system and veterans health administration joint initiative project.
As acupressure decreases pain, acupuncture may improve some aspects of quality of life for women with primary dysmenorrhea: A systematic review with meta-analysis.
Journal of Acupuncture and Meridian Studies.2015; 8: 220-228
Auricular acupuncture for chronic back pain in adults: A systematic review and metanalysis.
Revista da Escola de Engermagem da USP.2019; 53(Acupuntura auricular para dor cronica nas costas em adultos: revisao sistematica e metanalise.): e03461
), the literature on the biological mechanisms of the analgesic effects of auricular acupuncture/APA is limited. The gaps between APA effectiveness and mechanistic research have significantly hindered the acceptance of APA by the mainstream health care system and have limited its application in clinical settings.
Stimulation of ear points may cause a broad spectrum of systemic effects, such as modulation of inflammatory cytokine levels, which may explain pain relief (
). Multiple APA studies have shown a decrease in pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) among patients with axial neck pain after anterior cervical discectomy and fusion (
). These finding suggest that the effect of APA on chronic pain might be achieved through neuroimmune signaling. While studies have shown promising findings of the effect of APA on inflammatory biomarkers, the interpretation of these findings is limited owing to the exploratory nature of the studies (small sample size) (
Because of the persistent nature of pain in many chronic conditions (e.g., cancer, fibromyalgia, back pain), the underlying mechanism is believed to be modulated by increasing responsiveness of peripheral nociceptive neurons (peripheral sensitization) and nociceptive neurons in the central nervous system (central sensitization) (
). To enhance our understanding of the effect of APA on the mechanism of pain relief among patients with chronic pain conditions, we conducted a secondary data analysis of three pilot studies that tested the ability of APA to manage pain among patients with chronic low back pain (n = 61) (
). The purpose of this secondary data analysis was to further identify candidate inflammatory biomarkers of the mechanisms of APA on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers. In this article, we report the results on within-subject treatment effects (changes in scores from pre- to post-APA intervention) and between-group differences (changes in scores from pre- to post-intervention between targeted-point APA [T-APA] and non-targeted-point APA [NT-APA]), and correlations among pain intensity, interference, and biomarkers.
Methods
Table 1 summarizes the designs, samples, and data collection information of the three pilot studies included (
). All three studies were approved by the university's Institutional Review Board. All study participants received interventionist-administered APA weekly for four weeks. Data were collected at pre- and post-intervention. All participants received four weekly APA treatments depending on the assigned study intervention (T-APA or NT-APA). For the low back pain study, the intervention included two study groups (T-APA or NT-APA) (
The APA intervention included one treatment per week for four consecutive weeks. Auricular points on participants’ ears were detected with an electrical acupoint finder, which measures auricular cutaneous resistance to identify the potential acupoints for treatment. Ear points for T-APA included three for alleviating stress and pain (i.e., Shenmen, sympathetic, and nervous subcortex) and corresponding points to the anatomical sites (i.e., lower back, foot, or hand), depending on the body symptom (
). Bilateral auricular points were identified for treatment. Vaccaria seeds (natural, non-toxic botanical seeds of no medicinal value, ≈ 2 mm in diameter) were placed on the ear points for stimulation, and small pieces of waterproof tape (≈ 6 mm2) were used to secure the seeds onto the ears. In our previously published APA protocol (
), participants were told to press/stimulate the seeds taped to the acupoints on their ears at least three times per day for three minutes each time. The seeds and tape were removed at the end of the fifth day each week to regain point sensitivity prior to the next treatment. The endpoint was the measure of pain intensity and pain interference after the completion of the four-week APA. All study participants received the same APA intervention process.
NT-APA Group
The acupoints selected for the NT-APA group were located away from the site where the participant was experiencing low back pain and included the stomach, mouth, duodenum, and kidney (
). Worst pain intensity is a 0-10-point numerical rating scale in the past seven days (0 = “no pain at all”-10 “the worst pain ever possible”). The pain interference subscale of the BPI-sf is composed of seven items on a 0-10-point scale assessing the effect of pain on daily function in the past seven days (0 = “Does not interfere”-10 = “Completely interferes). The reliability and validity of the BPI-sf have been cited in more than 400 publications (
The circulating levels of inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α), β-endorphin, and calcitonin gene-related peptide (CGRP) were measured. The detailed blood sample collection, extraction, and testing processes were published in a previous manuscript (
The assumption of the normal distribution of the data was checked. The square-root transformation for the pain interference scores and log-transformation for all biomarkers were used to reduce the skewness of the data before data analyses. Descriptive analysis was used to display the outcomes measurements (including inflammatory biomarkers, pain intensity, and pain interference). Within-subject changes were examined using the changes in scores from pre- to post-intervention for individual subjects in each study group. Between-group differences were examined using the within-subject changes in scores from pre- to post-intervention between the T-APA and NT-APA groups (in only the low back pain study). The Mann-Whitney U Test was used to examine the difference in between-group score changes (T-APA versus NT-APA in the back pain study). Effect size as the standardized differences in the mean between two means (Cohen's d: between-group = the mean score change in the T-APA group compared to the NT-APA group in the low back pain study; within-group = the mean score change from pre-intervention to post-intervention) was calculated to estimate the sample sizes for future randomized controlled trials. The Wilcoxon signed-rank test was performed to test the null hypothesis of no difference in outcome measures between pre- and post-intervention for each study group (within-group difference). Spearman's rank correlation coefficient was used to examine the relationship between clinical outcomes (pain intensity and interference) and biomarkers. Significance was set at a p value < .05 for the data analysis and the multiple testing was not adjusted. All data analyses were performed using SAS 9.4 and R-4.2.0.
Results
Characteristics of the Study Participants
In total, 96 study participants were included (n = 61 patients with chronic low back pain, n = 20 breast cancer patients with arthralgia, and n = 15 cancer patients with chemotherapy-induced neuropathy) (Table 1). Most of the study participants were White (82%) and female (68% in the chronic low back pain study and 73% of the cancer patients with chemotherapy-induced neuropathy). Their ages ranged from 35-71 years.
Clinical Outcomes and Biomarkers
Table 2 presents data on clinical outcomes (pain intensity and pain interference) and biomarkers at pre- and post-APA treatment, within-subject changes (the change score between pre- and post-intervention) in biomarkers, pain intensity, and pain interference for each group (T-APA versus NT-APA), and between-group differences (the change in scores between pre- and post-intervention between the T-APA and NT-APA groups in the back pain study). Scores on all the study outcomes (pain intensity, pain interference, and biomarkers) decreased from pre-intervention to post-intervention. The only exceptions were TNF-α and IL-4 in the APA back pain group, whereby TNF-α increased and IL-4 did not change after the intervention.
Table 2Summary Statistics of Auricular Point Acupressure Effect on Pain Intensity, Pain Interference, and Inflammatory Biomarkers.
Between-group effect size= (Mt-Ms)/σpooled. Mt mean change score for T-APA-Back group, Ms mean change score for NT-APA group (or th. σpooled = √[((nt-1)σt2+(ns-1)σs2)/(nt+ns)-2], nt = the sample size for T-APA-Back group, ns = the sample size for NT-APA group, σt = standard deviation of change score for T-APA-Back group, σs = standard deviation of change sccore for NT-APA group.
Within-group effect size= (Mpost-Mpre)/σpooled. Mpost mean score of post-, Mpre mean score of pre- (or σpooled = √[((npost-1)σpost2+(npre-1)σpre2)/(npost+npre)-2], npost = the sample size for post-, npre = the sample size for the pre-, σpost = standard deviation of post-, σpre = standard deviation of of the post-. APA = auricular point acupressure; T-APA = targeted-point APA; NT-APA = non-targeted-point APA; SD = standard deviation; CGRP = calcitonin gene-related peptide; p = Mann-Whitney U Test (between T-APA-Back and NT-APA) and Wilcoxon signed rank test (within-group differences).
Mean ± SD (p value)
Effect Sizea
Pro-inflammatory Cytokines
IL-1β
T-APA-Back (n=30)
2.61 ± 0.56
2.54 ± 0.53
-0.07 ± 0.25 (0.14)
-0.12
-0.03 ± 0.19 (0.57)
-0.15
T-APA-Cancer (n=35)
2.43 ± 1.47
2.39 ± 1.43
-0.04 ± 0.40 (0.48)
-0.03
NT-APA (n=31)
2.60 ± 0.62
2.56 ± 0.62
-0.04 ± 0.10 (0.08)
-0.06
IL-2
T-APA-Back (n=30)
2.71 ± 0.56
2.66 ± 0.52
-0.05 ± 0.28 (0.66)
-0.09
0.02 ± 0.22 (0.78)
0.07
T-APA-Cancer (n=35)
3.38 ± 0.57
2.98 ± 1.10
-0.40 ± 0.98 (0.06)
-0.45
NT-APA (n=31)
2.70 ± 0.69
2.64 ± 0.71
-0.07 ± 0.10 (0.002)
-0.09
IL-6
T-APA-Back (n=30)
3.38 ± 0.51
3.30 ± 0.54
-0.08 ± 0.37 (0.89)
-0.16
-0.01 ± 0.33 (0.89)
-0.04
T-APA-Cancer (n=35)
3.68 ± 0.79
3.42 ± 1.22
-0.26 ± 0.87 (0.27)
-0.25
NT-APA (n=31)
3.45 ± 0.50
3.38 ± 0.53
-0.07 ± 0.29 (0.39)
-0.14
TNF-α
T-APA-Back (n=30)
4.65 ± 0.36
4.67 ± 0.37
0.02 ± 0.16 (0.99)
0.05
0.05 ± 0.16 (0.27)
0.29
T-APA-Cancer (n=35)
4.19 ± 0.91
4.09 ± 0.94
-0.10 ± 0.24 (0.03)
-0.11
NT-APA (n=31)
4.75 ± 0.50
4.72 ± 0.45
-0.03 ± 0.17 (0.19)
-0.06
Anti-inflammatory Cytokines
IL-4
T-APA-Back (n=30)
2.79 ± 0.53
2.79 ± 0.55
0.00 ± 0.10 (0.97)
0.01
0.04 ± 0.13 (0.20)
0.35
T-APA-Cancer (n=35)
2.89 ± 0.32
2.86 ± 0.30
-0.03 ± 0.20 (0.56)
-0.08
NT-APA (n=31)
2.71 ± 0.42
2.67 ± 0.37
-0.04 ± 0.15 (0.22)
-0.10
IL-10
T-APA-Back (n=30)
3.33 ± 0.36
3.26 ± 0.32
-0.06 ± 0.19 (0.08)
-0.18
-0.03 ± 0.20 (0.62)
-0.13
T-APA-Cancer (n=35)
3.90 ± 0.83
3.69 ± 1.01
-0.21 ± 1.09 (0.18)
-0.23
NT-APA (n=31)
3.41 ± 0.36
3.38 ± 0.34
-0.04 ± 0.21 (0.42)
-0.10
Neuropeptides
CGRP
T-APA-Back (n=30)
2.62 ± 1.76
2.55 ± 1.63
-0.07 ± 0.38 (0.40)
-0.04
-0.04 ± 0.35 (0.71)
-0.11
NT-APA-Back (n=31)
2.99 ± 1.31
2.95 ± 1.46
-0.03 ± 0.31 (0.52)
-0.02
Endorphin
T-APA-Back (n=30)
4.88 ± 0.30
4.82 ± 0.29
-0.06 ± 0.14 (0.04)
-0.20
-0.01 ± 0.17 (0.83)
-0.06
NT-APA-Back (n=31)
4.76 ± 0.29
4.71 ± 0.21
-0.05 ± 0.20 (0.08)
-0.20
Clinical Outcomes
Pain Intensity
T-APA-Back (n=30)
6.31 ± 1.93
2.44 ± 2.23
-3.88 ± 2.93 (<0.0001)
-1.86
-3.05 ± 2.75 (<0.0001)
-1.11
T-APA-Cancer (n=35)
6.94 ± 2.46
3.21 ± 2.37
-3.73 ± 2.18 (<0.0001)
-1.54
NT-APA (n=31)
6.07 ± 1.71
5.24 ± 2.44
-0.83 ± 2.55 (<0.0001)
-0.39
Pain Interference
T-APA-Back (n=30)
2.26 ± 0.46
2.60 ± 1.88
-0.38 ± 0.47 (<0.0001)
-0.64
0.23 ± 0.57 (0.12)
0.41
T-APA-Cancer (n=35)
3.26 ± 2.37
4.36 ± 1.97
-1.29 ± 1.69 (<0.0001)
-0.61
NT-APA (n=31)
2.12 ± 0.40
2.35 ± 1.51
-0.61 ± 0.66 (<0.0001)
-0.91
a Between-group effect size= (Mt-Ms)/σpooled. Mt mean change score for T-APA-Back group, Ms mean change score for NT-APA group (or th. σpooled = √[((nt-1)σt2+(ns-1)σs2)/(nt+ns)-2], nt = the sample size for T-APA-Back group, ns = the sample size for NT-APA group, σt = standard deviation of change score for T-APA-Back group, σs = standard deviation of change sccore for NT-APA group.
b Within-group effect size= (Mpost-Mpre)/σpooled. Mpost mean score of post-, Mpre mean score of pre- (or σpooled = √[((npost-1)σpost2+(npre-1)σpre2)/(npost+npre)-2], npost = the sample size for post-, npre = the sample size for the pre-, σpost = standard deviation of post-, σpre = standard deviation of of the post-.APA = auricular point acupressure; T-APA = targeted-point APA; NT-APA = non-targeted-point APA; SD = standard deviation; CGRP = calcitonin gene-related peptide; p = Mann-Whitney U Test (between T-APA-Back and NT-APA) and Wilcoxon signed rank test (within-group differences).
Within-group Changes in Biomarkers After Intervention
Within-subject analyses revealed statistically significant changes in three biomarkers: TNF-α (cancer pain in the T-APA group, p = .03), β-endorphin (low back pain in the T-APA group, p = .04), and IL-2 (low back pain in the NT-APA group, p = .002). Four biomarkers achieved the change with borderline significance (p value between .05-.10): IL-2 (cancer pain in the T-APA group, p = 0.06), IL-10 (low back pain in the T-APA group, p = 0.08), IL-1β (low back pain in the NT-APA group, p = .08), and β-endorphin (low back pain in the NT-APA group, p = 0.08). IL-6 had an effect size of –0.25 while the p value was .27 in the cancer pain APA group.
Between-group Differences
Using the within-group changes in biomarker scores (pre- and post-intervention) between the T-APA and NT-APA groups in the low back pain groups, IL-4 had the largest effect size (0.35), followed by TNF-α (0.29). Three biomarkers had effect sizes greater than 0.10 (IL-1β = 0.15; IL-10 = 0.13; and CGRP = 0.11). Other biomarkers had an effect size smaller than 0.10.
Correlations Among Biomarkers, Pain Intensity, and Pain Interference
Table 3 shows the Spearman's rank correlation coefficients among pain intensity, pain interference, and inflammatory biomarkers on the change in scores after treatment for all subjects. A strong positive monotonic relationship was detected between IL-1β and IL-2 (Spearman's ρ = 0.66). Moderate positive monotonic relationships were detected between IL-1β and IL-6 (Spearman's ρ = 0.41), between IL-1β and CGRP (Spearman's ρ = 0.41), between IL-2 and IL-6 (Spearman's ρ = 0.48), between IL-2 and IL-10 (Spearman's ρ = 0.43), between IL-6 and IL-10 (Spearman's ρ = 0.57), and between TNF-α and IL-10 (Spearman's ρ = 0.41). Figure 1 presents the scatter plot for outcome measures with statistically significant Spearman's rank correlation coefficients.
Table 3Spearman Rank Correlation among Pain Intensity, Pain Interference, and Inflammatory Biomarkers.
The findings of this secondary data analysis from our three pilot studies showed significant improvements in self-reported data (pain intensity and pain interference), significant changes in levels of TNF-α, β-endorphin, and IL-2 from pre- to post-intervention (within-group differences), significant between-group differences in IL-4 and TNF-α (changes from pre- to post-intervention between the T-APA group and NT-APA group), and strong correlations between IL-1β and IL-2, thereby contributing to a better understanding of the role of APA in pain relief via the inflammatory pathway.
The current findings from different chronic pain conditions support the notion that APA may modulate inflammatory biomarkers and consequently lead to the reduction of pain intensity and pain interference.Consistent with other findings, we speculate that APA may affect pain by modulating the type 1 helper T cells and macrophages to reduce pro-inflammatory cytokines that augment pain signals in many chronic pain conditions (
Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: A prospective randomized study.
Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: A prospective randomized study.
). While the mechanism of APA on reducing pro-inflammatory cytokines is unclear, we speculate that ear point stimulation causes vasodilation effects via the release of neuropeptide-induced local anti-inflammatory cytokines that could lead to the reduction of pro-inflammatory cytokines. These responses are modulated by mediators of inflammatory biomarkers and could explain the analgesic effects of APA on chronic pain.
While the current analysis enhances our understanding of the effect of APA on inflammatory biomarkers, why the stimulation of the ear points leads to pain relief remains unclear. Recent advances in functional magnetic resonance imaging (fMRI) have provided a useful tool to understand this knowledge gap. For example, stimulation of the ear thumb point produced significant fMRI activity in the thumb region of the somatosensory cortex (
Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: A clinical guideline from the American College of Physicians and American Academy of Family Physicians.
), making APA an attractive pain treatment. The immediate pain relief from APA has yet to be clearly explained. We previously conducted an fMRI study to observe brain activity after APA stimulation (
Dynamic brain activity change after auricular point acupressure on patients with chemotherapy-induced peripheral neuropathy: A pilot longitudinal functional magnetic resonance imaging study.
Global Advances in Health and Medicine.2020; 9: 1-9
). The results showed that APA can modulate the brain connectivity of the salience network (a brain network for the integration of sensory, emotional, and cognitive information) (
). These findings provide a theoretical basis for the neural mechanism of APA in pain processing. We speculate that overlapped cutaneous nerves in the outer ear (i.e., auricular branch of the vagus nerve, the auriculotemporal nerve, and the great auricular nerve) correspond to specific areas of the brain to confer immediate pain relief from ear point stimulation. Specifically, we posit that these areas have a reflex connection with specific parts of the body, and that stimulating ear points provides therapeutic effects.
Implications for Nursing and Pain Management
The current findings advance our basic scientific understanding of the inflammatory pathway underlying the effects of APA on pain relief and could facilitate the acceptance of APA by mainstream healthcare providers. Unlike acupuncture, which is a passive treatment, APA is a noninvasive, low-cost technique and engages patients to apply pressure to points on their ears to self-manage pain anywhere, anytime. Moreover, compared to acupuncture, APA is more accessible to patients because it can be administered by health practitioners with brief training and is feasible to scale up. APA is not yet widely available in U.S. healthcare systems, and we received an overwhelming number of requests from former study participants for further APA treatment. To scale up, maximizing the usability and accessibility of APA, we have conducted pilot studies using a smartphone app to support self-administered APA for pain, which featured instructional and demonstrational videos (
). The current study sets the foundation for future work to test the endogenous biomarkers and critically elucidate the mechanism of APA on pain relief.
Limitations
Because of the complex interaction among inflammatory biomarkers in chronic pain (
), the study findings should be interpreted in light of limitations, including the nature of the secondary data analysis (i.e., the combination of data from different chronic pain conditions), a lack of comparison of APA data in the cancer pain group, a lack of long-term follow-up data (i.e., only pre- and post-intervention data were included), and a lack of the control of confounding in inflammatory biomarkers. For example, cytokines and chemokines have short half-lives that vary from two-six hours (
), and information regarding circadian rhythms and other clinical characteristics (e.g., acute illness/ trauma, immune disease, medication use, nutrition, endocrine/metabolic disease) was not available.
Conclusions
Based on our findings, APA shows great promise to reverse chronic pain through an inflammatory mechanism, i.e., it exhibits anti-inflammatory efficacy by blocking pro-inflammatory cytokines (TNF-α, IL-2) or releasing anti-inflammatory cytokines (IL-4) or β-endorphins. More work is needed to understand the complex nature of these biological, psychophysiological, and genetic relationships. Future larger-scale research should investigate the effect of these biomarkers on the analgesic effects of APA in a rigorous mechanism study using a randomized control trial and ear point specificity-control.
Declaration of interests
None.
Acknowledgements
Research reported in this publication was supported by grants to Dr. Chao Hsing Yeh from Under Armour Women's Health & Breast Cancer Innovation Grant, Johns Hopkins Medicine, and the National Institute on Aging of the National Institutes of Health (R01AG056587).
References
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As acupressure decreases pain, acupuncture may improve some aspects of quality of life for women with primary dysmenorrhea: A systematic review with meta-analysis.
Journal of Acupuncture and Meridian Studies.2015; 8: 220-228
Comparative Effectiveness Review No. 229. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 20-EHC011.
(Opioid Treatments for Chronic Pain) Agency for Healthcare Research and Quality,
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Auricular acupuncture for chronic back pain in adults: A systematic review and metanalysis.
Revista da Escola de Engermagem da USP.2019; 53(Acupuntura auricular para dor cronica nas costas em adultos: revisao sistematica e metanalise.): e03461
Eighteen-year trends in the prevalence of, and health care use for, noncancer pain in the United States: Data from the Medical Expenditure Panel Survey.
National Acupuncture Detoxification Association. (2010). Training resource manual: A handbook for individuals training in the National Acupuncture Detoxification Association's Five-needle Acudetox Protocol (4th ed.).
Building capacity for complementary and integrative medicine through a large, cross-agency, acupuncture training program: Lessons learned from a military health system and veterans health administration joint initiative project.
Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: A prospective randomized study.
Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: A clinical guideline from the American College of Physicians and American Academy of Family Physicians.
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Global Advances in Health and Medicine.2020; 9: 1-9
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