Auricular Therapy for Migraine.

PURPOSE OF REVIEW: Migraine brings hours or even days of disability, affecting 15% of the US population and one billion people worldwide. Migraine treatments have improved over the years and there is now a range of non-pharmacologic therapies that can be administered as monotherapy, combined with pharmacologic therapy or combined with other non-pharmacologic therapies to give greater options for those who do not tolerate, do not respond to, or who wish to reduce or avoid pharmacologic treatments. RECENT FINDINGS: We conducted a review of the literature on auricular therapy as acute or preventive treatment for migraine, searching the databases of MEDLINE and ClinicalTrials.gov from 2013 to 2023. A total of 43 articles contained at least one search term, with three studies specific to acute or prevention of migraine (one for acute only, one for prevention only and one for both acute and prevention). The population was limited to, adults with migraine ages 18 or older, with the administration of auricular therapy as the intervention. While there have been studies on the use of auricular therapy for pain on two specific standardized auricular therapies, Battlefield Acupuncture (BFA) and National Acupuncture Detoxification Association (NADA), neither of these protocols were utilized in any of the studies specific to migraine management. Each of the three studies used different techniques, with one using acupuncture needles and five specific points and two using semi-permanent needles (remained in for a few days) that were placed in areas that showed high activity. Each of these studies showed auricular therapy to have benefit for the management of migraine. However, the authors of each of the studies recommended further studies. Auricular therapy may be a helpful adjunctive treatment to abort a current migraine attack or aid in reducing the frequency or severity of migraine attacks.

[Deep learning approach for automatic segmentation of auricular acupoint divisions].

The automatic segmentation of auricular acupoint divisions is the basis for realizing intelligent auricular acupoint therapy. However, due to the large number of ear acupuncture areas and the lack of clear boundary, existing solutions face challenges in automatically segmenting auricular acupoints. Therefore, a fast and accurate automatic segmentation approach of auricular acupuncture divisions is needed. A deep learning-based approach for automatic segmentation of auricular acupoint divisions is proposed, which mainly includes three stages: ear contour detection, anatomical part segmentation and keypoints localization, and image post-processing. In the anatomical part segmentation and keypoints localization stages, K-YOLACT was proposed to improve operating efficiency. Experimental results showed that the proposed approach achieved automatic segmentation of 66 acupuncture points in the frontal image of the ear, and the segmentation effect was better than existing solutions. At the same time, the mean average precision (mAP) of the anatomical part segmentation of the K-YOLACT was 83.2%, mAP of keypoints localization was 98.1%, and the running speed was significantly improved. The implementation of this approach provides a reliable solution for the accurate segmentation of auricular point images, and provides strong technical support for the modern development of traditional Chinese medicine.

Treating pain using acupuncture for nonacupuncturists.

ABSTRACT: Battlefield acupuncture is a specific auricular acupuncture protocol that can be performed by nonacupuncturists in military and civilian clinical settings. Battlefield acupuncture is purported to be efficacious in controlling pain, is quickly administered, and requires minimal postadministration observation. With very low risk and a negligible adverse reaction profile, this technique can be used as an alternative or complement to manage pain. More large randomized controlled trials are needed to compare acupuncture with standard therapy in military and civilian settings.

Battlefield Acupuncture as a Treatment for Pain.

This study evaluated both randomized and nonrandomized trials of battlefield acupuncture for the treatment of both acute and chronic pain. Studies published between May 2016 and November 2019 were found through PubMed, the Cochrane Library, or Scopus, concerned with the treatment of pain using auricular acupuncture in accordance with battlefield acupuncture protocol. Search terms were battlefield acupuncture AND pain or auricular acupuncture AND pain. Case reports, literature reviews, meta-analyses, and expert opinions were not included. Bias risk was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. We found 12 studies with a combined sample size of 12,326. All five of the included nonrandomized trials reported positive outcomes, while five of seven of the included randomized trials reached statistical significance in their primary outcome. Six of the randomized trials were considered to have a high risk of bias resulting from the lack of blinding. The one randomized trial with moderate bias risk was a positive study. No severe adverse events were reported. Clinicians may consider battlefield acupuncture as a safe treatment for pain while the evidence base grows; however, we conclude that widespread adoption of battlefield acupuncture will require further high-quality studies drawing from diverse settings and patient populations. In addition, future studies should attempt to achieve blinding.

Provider Perspectives of Battlefield Acupuncture: Advantages, Disadvantages and Its Potential Role in Reducing Opioid Use for Pain.

OBJECTIVES: Nonpharmacological options to treat pain are in demand, in part to address the opioid crisis. One such option is acupuncture. Battlefield acupuncture (BFA) is an auricular needling protocol currently used to treat pain in the Veterans Health Administration. We aimed to identify the advantages and disadvantages of BFA from providers' perspectives. METHODS: We rely on an inductive qualitative approach to explore provider perceptions through thematic analysis of semistructured interviews with 43 BFA providers across the nation. RESULTS: We identified the following themes. Disadvantages included: (1) clinical guidelines are insufficient; (2) patients often request multiple BFA visits from providers; (3) BFA can be uncomfortable; (4) BFA may not be an effective treatment option unless it can be provided "on demand"; and (5) BFA can promote euphoria, which can have deleterious consequences for patient self-care. Perceived advantages included: (1) BFA can simultaneously effectively control pain while reducing opioid use; (2) BFA may alleviate the pain that has been unsuccessfully treated by conventional methods; (3) BFA gives providers a treatment option to offer patients with substance use disorder; (4) BFA helps build a trusting patient-provider relationship; (5) BFA can create the opportunity for hope. CONCLUSIONS: Providers perceive BFA to have many benefits, both clinical and relational, including ways in which it may have utility in addressing the current opioid crisis. BFA is easy to deliver and has potential clinical and relational utility. Efforts to better understand effectiveness are warranted.

Does Offering Battlefield Acupuncture Lead to Subsequent Use of Traditional Acupuncture?

OBJECTIVES: Veterans Health Administration encourages auricular acupuncture (Battlefield Acupuncture/BFA) as a nonpharmacologic approach to pain management. Qualitative reports highlighted a "gateway hypothesis": providing BFA can lead to additional nonpharmacologic treatments. This analysis examines subsequent use of traditional acupuncture. RESEARCH DESIGN: Cohort study of Veterans treated with BFA and a propensity score matched comparison group with a 3-month follow-up period to identify subsequent use of traditional acupuncture. Matching variables included pain, comorbidity, and demographics, with further adjustment in multivariate regression analysis. SUBJECTS: We identified 41,234 patients who used BFA across 130 Veterans Health Administration medical facilities between October 1, 2016 and March 31, 2019. These patients were matched 2:1 on Veterans who used VA care but not BFA during the same period resulting in a population of 24,037 BFA users and a comparison cohort of 40,358 non-BFA users. Patients with prior use of traditional acupuncture were excluded. RESULTS: Among Veterans receiving BFA, 9.5% subsequently used traditional acupuncture compared with 0.9% of non-BFA users (P<0.001). In adjusted analysis, accounting for patient characteristics and regional availability of traditional acupuncture, patients who used BFA had 10.9 times greater odds (95% confidence interval, 8.67-12.24) of subsequent traditional acupuncture use. CONCLUSIONS: Providing BFA, which is easy to administer during a patient visit and does not require providers be formally certified, led to a substantial increase in use of traditional acupuncture. These findings suggest that the value of offering BFA may not only be its immediate potential for pain relief but also subsequent engagement in additional therapies.

Patient Feedback on the Effectiveness of Auricular Acupuncture on Pain in Routine Clinical Care: The Experience of 11,406 Veterans.

OBJECTIVES: Veterans Health Administration (VHA) launched a national initiative to train providers in a specific, protocolized auricular acupuncture treatment (also called Battlefield Acupuncture or BFA) as a nonpharmacological approach to pain management. This evaluation assessed the real-world effectiveness of BFA on immediate pain relief and identified subgroups of patients for whom BFA is most effective. RESEARCH DESIGN: In a cross-sectional cohort study, electronic medical record data for 11,406 Veterans treated with BFA at 57 VHA medical centers between October 2016 and September 2018 was analyzed. The multivariate analysis incorporated data on pain history, change in pain level on an 11-point scale, complications, and demographic information. METHODS: A total of 11,406 Veterans were treated with BFA at 57 VHA medical centers between October 2016 and September 2018 and had effectiveness data recorded in their electronic medical record. RESULTS: More than 3 quarters experienced immediate decreases in pain following administration of BFA, with nearly 60% reported experiencing a minimal clinically important difference in pain intensity. The average decrease in pain intensity was -2.5 points (SD=2.2) at the initial BFA treatment, and -2.2 points (SD=2.0) at subsequent treatments. BFA was effective across a wide range of Veterans with many having preexisting chronic pain, or physical, or psychological comorbid conditions. Veterans with opioid use in the year before BFA experienced less improvement, with pain intensity scores improving more among Veterans who had not recently used opioids. CONCLUSION: VHA's rapid expansion of training providers to offer BFA as a nonpharmacological approach to pain management has benefited many Veterans.

Auricular acupuncture for the treatment of nonepileptic seizures: A pilot study.

OBJECTIVE: The aim of this pilot study was to examine the safety and tolerability of an eight-week treatment of twice weekly auricular acupuncture as a therapeutic intervention for the treatment of psychogenic nonepileptic seizures (PNES). The secondary aim was to determine if auricular acupuncture was effective at reducing PNES event frequency. Psychogenic nonepileptic seizures are as common as multiple sclerosis and are highly resistant to intervention. Unfortunately, there is no standard of care therapy, although mental health treatment referrals are commonly made. Acupuncture is felt to be a safe and cost-effective treatment for many diseases and symptoms including mental health disorders such as posttraumatic stress disorder (PTSD), anxiety, and conversion disorders. We propose to examine auricular acupuncture as a treatment for PNES. METHODS: A single-center, 16-week trial of auricular acupuncture was designed: a four-week baseline period, followed by an eight-week active treatment period during which subjects received twice weekly auricular acupuncture, then followed by a four-week washout period. Tolerability was defined as completion of 12 of 16 treatments. Successful compliance with seizure diary was defined as >80%, or 100 of 120 days completed. Safety profile was established and seizure count per week was also calculated. RESULTS: A total of 29 subjects enrolled from a consecutive sample of 73 PNES diagnoses discharging from our epilepsy unit. Twenty-two subjects entered the study with 91% completing more than 12 of 16 treatments, 91% meeting the endpoint of completing >80% of diary entries. Adverse events were mild, and only two subjects were withdrawn due to increased PNES frequency. Although short-term in design, using one-way repeated measures analysis of variance (ANOVA), we observed a statistically significant reduction in seizure count from baseline at treatment month one, treatment month two, and at the washout period (p = 0.0083). Eleven of 12 subjects (52.3%) who received at least one treatment recorded a 50% frequency reduction. Three of 21 subjects (14%) were PNES-free at the end of the study. SIGNIFICANCE: Auricular acupuncture is well-tolerated in a population with PNES and exhibits similar event frequency reductions as cognitive behavioral therapy (CBT). We believe that this is the first literature report examining auricular acupuncture for the treatment of PNES.

Acupuncture for Migraine: a Review of the Data and Clinical Insights.

PURPOSE OF REVIEW: The purpose of this review is to discuss the current evidence for acupuncture in migraine and to provide insight into which patients may benefit most from acupuncture. RECENT FINDINGS: Multiple studies support acupuncture as a validated modality for the prevention of episodic migraine. While small studies on acupuncture for the prevention of chronic migraine are encouraging, evidence for its benefit is limited. Likewise, the existing studies on acupuncture for acute migraine treatment are insufficient. Acupuncture is commonly used to treat migraine and has gained popularity as a validated non-pharmaceutical option. Although the specific mechanisms of acupuncture are not clearly understood, there is evidence for its effectiveness in treating migraine. Results of acupuncture studies are quite variable and depend on multiple factors, including frequency, duration, and consistency of treatments, as well as acupoint selection. A better understanding of the flaws inherent in acupuncture research will help guide the development of future studies.

Correlations Between Auricular Tenderness and Symptoms in Korean Adults.

The purpose of this study was to examine the correlation between auricular tenderness and subjective symptoms. A descriptive correlational study design was followed, which was also the second analysis of a randomized controlled trial. This study was performed in the Republic of Korea from September 2013 to February 2017. The Patient Health Questionnaire-9, the Constipation Assessment Scale, and the Nicotine Dependence Syndrome Scale were used. One hundred thirty-three participants displayed ear tenderness, whereas 84 participants did not. Adults with auricular tenderness reported more symptoms, such as sputum, rhinitis, constipation, stress, mood swings, and depressive symptoms compared with adults without (with tenderness: 4.14 ± 2.94, without tenderness: 2.92 ± 2.45; t = 3.32, P = .001). Finally, auricular acupressure points were positively correlated with various symptoms such as sputum, constipation, nicotine addiction, stress, cough, and rhinitis. Auricular palpation could be used to detect a disease at an early stage.

The Effect of Auricular Acupressure and Positive Group Psychotherapy With Motivational Interviewing for Smoking Cessation in Korean Adults.

The aim of this study was to investigate the effects of positive group psychotherapy with auricular acupressure on tobacco withdrawal symptoms and smoking cessation. This study used a randomized controlled trial design. Participants were randomly assigned to 1 of 3 groups: group 1 (counseling and auricular acupressure), group 2 (counseling and placebo acupressure), and the control group (self-help for smoking cessation). Positive group psychotherapy and auricular acupressure were performed once a week for 6 weeks. The smoking cessation rates for 1 year in groups 1 and 2 were higher than that in the control group (9.5%, 15.6%, and 0%, respectively; odd ratio: 7.98, P = .019, n = 109). There was a significant difference of tobacco withdrawal symptoms among the 3 groups over 4 weeks (F = 2.9, P = .04). The mean differences between week 1 and week 4 among the 3 groups were statistically significant (4.7 ± 6.96, 5.18 ± 7.9, and 0.14 ± 7.15, F = 4.25, P = .018).

Auricular acupuncture as effective pain relief after episiotomy: a randomized controlled pilot study.

PURPOSE: Previously, pain treatment following episiotomy has relied on non-steroid anti-inflammatory drugs as analgesics, whose use during breastfeeding remains controversial due of their transfer to the child. METHODS: This was a pilot randomized parallel single-center study aiming to evaluate the effects of auricular acupuncture on pain relief after episiotomy. The primary outcome was reduction of pain intensity using visual analogue scale (VAS) scores during the first three postpartum days. The patients were allocated to either of the groups by using a heads-tails binary result coin toss method and the allocation was not masked. The study was completed after including 60 healthy women that underwent mediolateral episiotomy performed during vaginal delivery, with 29 receiving acupuncture therapy and 31 not receiving acupuncture therapy for pain relief. Oral analgesic therapy was made available per request for all patients. RESULTS: This study showed that subjective experience of pain was significantly reduced in the acupuncture group on the second and third postpartum days (P = 0.004, P = 0.005, P = 0.22). There were no adverse effects of acupuncture noted. CONCLUSIONS: Our findings confirm that auricular acupuncture therapy may be a valuable adjunct to analgesic therapy in patients undergoing episiotomy during vaginal delivery. The results prompt a question whether our current 'best practice' may yet be improved.

Effects of Auricular Acupressure on Pain Management: A Systematic Review.

OBJECTIVE: Nearly half of hospitalized patients in the United States have reported experiencing pain even while undergoing treatment for pain. Analgesic use is the most common type of treatment for pain management. Many patients who experience pain seek nonpharmacologic interventions to manage their pain, including forms of complementary or alternative medicine such as auricular acupressure (AA). DESIGN: This study conducted the first systematic review of the studies that have evaluated the effect of AA as an adjunct on pain management. DATA SOURCES: We searched PubMed, CINAHL, Embase, Google Scholar, and Wiley for randomized controlled trials on AA. REVIEW/ANALYSIS METHODS: The pain outcomes were pain severity and analgesic consumption. Methodologic quality was also evaluated. Fifteen randomized controlled trials were included in this analysis. RESULTS: Twelve studies reported statistically significant improvement in the pain outcomes of AA treatment compared with the sham or standard care groups. When methodologic quality was assessed, the selected studies had medium quality, but there was a lack of high quality. This supports that the use of AA for patients may enhance self-management for their pain. However, the small number of studies and the lack of consistent rigorous methodology across the studies preclude definitive statements regarding the effectiveness of AA. CONCLUSION: The nursing implications based on this review is that education about AA and complementary or alternative medicine therapies for health care providers may assist them in providing pain control for their patients. In addition, we need to continue research to build on evidence on the effect of AA on pain management.

Effects of auricular acupressure on pain and disability in adults with chronic neck pain.

AIM: The aim of this study was to examine the effect of auricular acupressure (AA) on pain, pain threshold (PT), disability, and cervical range of motion in adults with chronic neck pain. BACKGROUND: About 30-50% of the world's population suffers from chronic neck pain, and the cost of treatment is increasing. MATERIALS AND METHODS: This single-blind, randomized sham-controlled study was conducted on 48 adults with chronic neck pain in South Korea. The experimental group (n = 25) received AA on specific acupoints for neck pain, whereas the control group (n = 23) received AA on unspecific acupoints. Participants received 4 weeks of auricular-acupressure intervention. Outcomes were assessed by the visual analog scale (VAS), PT, neck-disability index (NDI), and cervical range of motion. Measurements were taken 3 times: before intervention, 2 weeks into the intervention, and after the intervention. RESULTS: Statistical differences between the two groups emerged in PT (p = .003), the NDI (p = .033), cervical flexion (p = .004), and left rotation (p = .004), but not on the VAS. CONCLUSIONS: This study showed that AA leads to improvements on PT, neck disability, and cervical range of motion. Therefore, AA can be used as an alternative nursing intervention for chronic neck pain.

Combining Education With Auricular Acupressure to Facilitate Smoking Cessation in Young Adults.

Young adults rarely use pharmacotherapy to cease smoking. This prospective experimental study was performed using a nonpharmacotherapy design. Smoking cessation education combined with auricular acupressure may be more attractive. The key factor for superior smoking cessation was the decrease of nicotine dependence in the early stage of smoking cessation.

Effects of auricular acupuncture on chronic pain in people with back musculoskeletal disorders: a randomized clinical trial.

OBJECTIVE: To evaluate the effects of auricular acupuncture on pain intensity, its impact on daily activities, the relief provided by the intervention, and the pain threshold in people with back musculoskeletal disorders. METHODS: Randomized clinical trial carried out with people randomly allocated into three groups: treatment, placebo, and control. Evaluations were performed using the Brief Pain Inventory and a digital algometer before (initial) and after (final) the treatment and after a 15-day follow-up period. RESULTS: The sample was 110 people. There was a decrease in pain intensity in the treatment and placebo groups as revealed by the comparison between the initial and final evaluations (p<0.05), and in the treatment group in the comparison between the initial and follow-up evaluations (p<0.05). A decreased impact of pain on daily activities in the treatment and placebo groups over time was found (p<0.05). At the final evaluation, the impact of pain was lower in the treatment group (p<0.05). Auricular acupuncture did not increase the pain threshold. CONCLUSION: Auricular acupuncture presented positive effects by reducing the chronic pain intensity and its impact on daily activities in people with back musculoskeletal disorders. Brazilian Clinical Trials Registry: RBR-5X69X2.

Auricular Acupuncture for the Treatment of Pediatric Migraines in the Emergency Department.

OBJECTIVES: Headache remains a frequent complaint for children presenting to a pediatric emergency department (ED). Typical treatments include oral or intravenous medications, but do not always relieve pain. An alternative intervention is auricular acupuncture. It has been shown to be effective in the treatment of migraines in adults. The objective of this study was to evaluate the utility and adverse effects of auricular acupuncture in the treatment of pediatric migraines in the ED. METHODS: This was a prospective, interventional, cohort study of patients 8 to 18 years of age. Efficacious ear points were located by needle contact or electrical point finder with attention to 2 migraine lines on the ear. ASP gold semipermanent ear needles were placed in the efficacious points and patients were monitored for 15 minutes. The primary outcome was the change in preintervention and postintervention pain scores using a numerical self-reported pain visual analog scale (VAS). RESULTS: Nineteen patients elected to enroll in the study. The mean change in the VAS scores was both clinically and statistically significant at 7.03 (interquartile range, 6-8.5) with a P value of less than 0.001. Two patients elected to withdraw from the study secondary to incomplete resolution of migraine pain despite improvement in VAS scores. There were no known adverse events. CONCLUSIONS: With all subjects showing improvement or resolution of migraine headache, this pilot study introduces an alternative intervention to pediatric migraine management. Further studies are needed to evaluate the duration of symptom resolution and comparative effectiveness; auricular acupuncture seems to be a valid alternative.

Therapeutic effects of targeted nursing interventions combined with auricular-plaster therapy on anxiety level and life quality of Hepatitis B patients.

Mood disorders are common problems in patients with chronic hepatitis B virus (HBV) infection, most clinical treatment focus on anti-viral and anti-fibrosis rather than taking care of mood disorders. In the past decades, we have developed a Chinese medicine treatment method together with nursing intervention, which shows a positive treatment effect on patients. 158 cases of hepatitis B patients were randomly divided into one control group (78 cases), and one observation group (80 cases). The patients in control group received hepatology nursing, liver protecting and transaminase lowering medicine, and ear acupoint bean pressing treatment. In addition to the nursing and treatment as the control group, the patients in observation group were given targeted nursing interventions, including psychological intervention, emotional intervention, cognitive intervention, and systematic family and community support intervention. The anxiety level and sleep quality of patients in both groups were compared. The improvement of hepatic indexes was checked and life qualities in both groups were also compared. Compared to the control group, the patients in the observation group provided have statistically significant mprovement on anxiety control, sleep quality, and hepatic indexes changes (P<0.05). The observation group also showed remarkably better life quality scores (GQLI-64) than the control group (P<0.01). This research confirmed that targeted nursing intervention coupled with ear acupoint bean pressing showed effective improvement on the anxiety control and sleep quality of chronic hepatic B patients, and demonstrated better hepatic index recovery. Patients in the observation group also have higher life quality scores than the control group.

Effectiveness of auricular acupuncture in the treatment of cancer pain: randomized clinical trial. / Efetividade da acupuntura auricular no tratamento da dor oncológica: ensaio clínico randomizado.

OBJECTIVE: To evaluate the effectiveness of auricular acupuncture in the pain of cancer patients receiving chemotherapy and to verify if there were alterations in the use of analgesics after the application of this intervention. METHOD: Randomized controlled trial with cancer patients with complaints of pain greater than or equal to four in the Numerical Pain Scale. Two parallel groups were created, an Experimental group, which received auricular acupuncture at energy balance points and at points indicated for the treatment of pain, and a Placebo group, in which fixed placebo points were used. Both groups received the application of semipermanent needles in eight sessions. RESULTS: 31 cancer patients participated in the study. After the eight auricular acupuncture sessions, there was a significant difference between the groups regarding the reduction of pain intensity (p < 0.001) and of the use of medications (p < 0.05). CONCLUSION: Auricular acupuncture was effective in reducing the pain of patients receiving chemotherapy. Brazilian Registry of Clinical Trials: RBR-6k3rqh.

Ear Acupuncture for Immediate Pain Relief-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To systematically review the literature on the effectiveness of ear acupuncture (EA) for immediate pain relief. Data sources: AMED, CINAHL, Cochrane Reviews, Embase, PsycINFO, PubMed, Scopus Web of Science, from inception through March 2015. Study selection: English publications, randomized controlled trials on human subjects involving EA as a treatment for pain, with outcomes recorded within 48 hours. Data extraction and design: Two authors independently assessed trial eligibility, quality, results, and side effects, and extracted data; a third author checked final data. Effect size (d), mean difference (MD), and 95% confidence interval (CI) were calculated. The Physiotherapy Evidence Database (PEDro) scoring system was used to assess study quality. Meta-analysis was performed for two primary outcomes measures-pain intensity score and analgesic requirements. Results: Ten studies met inclusion criteria. Quality per PEDro scores: four excellent, four good, two fair. Based on their primary outcome measures, six studies showed EA being superior to its comparator, three showed no difference to comparators (which in all cases were analgesics), and one study showed significant pain decrease at the first time point and no significant decrease at the second. Meta-analysis was completed for the three studies that evaluated pain intensity as a primary outcome measure, and EA was superior to comparator (MD = -0.96, 95% CI = -1.82- -0.11), but the MD was small. Meta-analysis was completed for the six studies that evaluated analgesic requirements, and EA was superior (MD = -1.08, 95% CI = -1.78- -0.38]), again with a small MD. Six studies reported side effects; all were minor and transient. Conclusions: Ear acupuncture may be a promising modality to be used for pain reduction within 48 hours, with a low side effect profile. Rigorous research is needed to establish definitive evidence of a clinically significant difference from controls or from other pain treatments.