Differential clinical characteristics across traditional Chinese medicine (TCM) syndromes in patients with sickle cell disease.

Background: Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effects for pain management in SCD. However, these clinical studies lack the guidance of Traditional Chinese Medicine (TCM) Syndrome Differentiation principles for treatment. Aim: To characterize differences in clinical presentation amongst TCM-diagnosed syndromes in SCD patients. Method: 52 patients with SCD and 28 age- and sex-matched healthy controls (HCs) were enrolled in an ongoing trial of acupuncture. Each participant completed a series of questionnaires on pain, physical function, fatigue, sleep, anxiety, depression, and QoL and underwent cold- and pressure-based quantitative sensory testing at baseline. Data on prescription opioid use over the 12 months prior to study enrollment was used to calculate mean daily morphine milligram equivalents (MME). Differences among the three TCM syndromes were analyzed by one-way ANOVA followed by Tukey post hoc testing. Two-sample t-tests were used to compare SCD and HC groups. Results: TCM diagnosis criteria classified SCD patients into one of three TCM syndromes: a) Equal; b) Deficiency; and c) Stagnation. The Stagnation group exhibited higher pain interference, physical dysfunction, nociplastic pain, fatigue, anxiety, depression, MME consumption, and lower sleep quality and QoL compared to the Equal group. Few differences were observed between HCs and the Equal SCD group across outcomes. Deficiency and Stagnation groups were differentiated with observed- and patient-reported clinical manifestations. Conclusion: These findings suggest that TCM-diagnosed syndromes in SCD can be differentially characterized using validated objective and patient-reported outcomes. Because characteristics of pain and co-morbidities in each SCD patient are unique, targeting specific TCM "syndromes" may facilitate treatment effectiveness with a syndrome-based personalized treatment plan that conforms to TCM principles. These findings lay the foundation for the development of tailored acupuncture interventions based on TCM syndromes for managing pain in SCD. Larger samples are required to further refine and validate TCM diagnostic criteria for SCD.

Mechanistic and thermal characterization of acupuncture for chemotherapy-induced peripheral neuropathy as measured by quantitative sensory testing.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST). METHODS: We conducted a randomized controlled trial of real acupuncture (RA) and sham acupuncture (SA) compared to usual care (UC) in cancer survivors with moderate-to-severe CIPN. Treatment response was assessed with QST measures of tactile and vibration detection thresholds in hands and feet, thermal detection, and pain thresholds at weeks 0, 8, and 12. Constrained linear mixed model (cLMM) regression was used for statistical analysis. RESULTS: 63 patients completed QST testing. At week 8, vibrational detection thresholds in feet were significantly lower in RA and SA (p = 0.019 and p = 0.046) than in UC, with no difference between RA and SA (p = 0.637). Both RA and SA also showed significantly higher cool thermal detection than UC (p = 0.008 and p = 0.013, respectively), with no difference between RA and SA (p = 0.790). No differences in tactile detection, vibrational detection in hands, warm thermal detection, and thermal pain thresholds were detected among the three arms at weeks 8 and 12. CONCLUSION: QST demonstrated different patterns in RA, SA, and UC. After eight weeks of RA, we observed significant improvements in the vibrational detection threshold in feet and cool thermal detection threshold in hands compared to UC. No significant differences were seen when compared to SA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03183037); June 9, 2017.

Differential clinical characteristics across traditional Chinese medicine (TCM) Syndromes in patients with sickle cell disease.

Background: Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effects for pain management in SCD. However, these clinical studies lack the guidance of Traditional Chinese Medicine (TCM) Syndrome Differentiation principles for treatment. Aim: To characterize differences in clinical presentation amongst TCM diagnosed Syndromes in SCD patients. Method: Fifty-two patients with SCD and 28 age- and sex-matched healthy controls (HCs) were enrolled in an ongoing trial of acupuncture. Each participant completed a series of questionnaires on pain, physical function, fatigue, sleep, anxiety, depression and QoL and underwent cold- and pressure-based quantitative sensory testing at baseline. Data on prescription opioid use over the 12 months prior to study enrollment was used to calculate mean daily morphine milligram equivalents (MME). Differences among the three TCM Syndromes were analyzed by one-way ANOVA followed by Tukey post hoc testing. Two-sample t-tests were used to compare SCD and HC groups. Results: TCM diagnosis criteria classified SCD patients into one of three TCM Syndromes: (a) Equal; (b) Deficiency; and (c) Stagnation. The Stagnation group exhibited higher pain interference, physical dysfunction, nociplastic pain, fatigue, anxiety, depression, MME consumption and lower sleep quality and QoL compared to the Equal group. Few differences were observed between HCs and the Equal SCD group across outcomes. Deficiency and Stagnation groups were differentiated with observed- and patient-reported clinical manifestations. Conclusion: These findings suggest that TCM diagnosed Syndromes in SCD can be differentially characterized using validated objective and patient-reported outcomes. Because characteristics of pain and co-morbidities in each SCD patient are unique, targeting specific TCM "Syndromes" may facilitate treatment effectiveness with a Syndrome-based personalized treatment plan that conforms to TCM principles. These findings lay the foundation for the development of tailored acupuncture interventions based on TCM Syndromes for managing pain in SCD. Larger samples are required to further refine and validate TCM diagnostic criteria for SCD.

Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ-Aminobutyric Acid: A Randomized Neuroimaging Trial.

OBJECTIVE: Acupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved. METHODS: Seventy-six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment. RESULTS: Fibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre- to posttreatment was -1.14 in the EA group versus -0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1leg ; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1leg -anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI (r = -0.44, P = 0.01) and increased levels of γ-aminobutyric acid (GABA+) in the anterior insula (r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI (r = -0.59, P = 0.01). Finally, post-EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1leg -anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval -0.533, -0.037). CONCLUSION: The somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.

Childhood Trauma Predicts Cancer Treatment-Related Pain in Breast Cancer Survivors.

BACKGROUND: Childhood trauma has been linked to neuropathic pain in noncancer populations, but its relationship with cancer treatment-related neuropathic pain is unknown. OBJECTIVE: This secondary data analysis of a prospective, longitudinal, observational study aimed to explore the relationship of childhood trauma experience with pain severity, pain interference, and neuropathic symptom severity (NSS) 12 months after surgery in women receiving treatment for stage 0 to III breast cancer. METHODS: Women (N = 44) recruited from a comprehensive cancer center self-reported childhood trauma experience, pain severity, pain interference, NSS, co-occurring symptoms, and pain beliefs via questionnaires. Descriptive statistics were used to describe childhood trauma experience. Linear regression was used to model childhood trauma and other predictors on pain variables 12 months after surgery. RESULTS: Childhood trauma predicted pain severity and pain interference 12 months after surgery (P < .05), as did baseline pain severities and helplessness-pain catastrophizing. Age predicted only NSS. Together, the best models predicted 31.6% to 40.9% of the variance in pain severities at 12 months (P < .001). CONCLUSIONS: Childhood trauma exposure was a significant predictor of pain 12 months after breast cancer surgery and adjuvant treatment. Younger and helplessness-pain catastrophizing women are also at risk. Research is needed to identify preventive neuropathic pain interventions for high-risk women. IMPLICATIONS FOR PRACTICE: Women receiving breast cancer treatment should proactively be assessed for childhood trauma history, possibly by using discreet previsit questionnaires. Childhood trauma survivors may be at high risk for poor pain outcomes and may benefit from tailored pain interventions.

Pressure Pain Phenotypes in Women Before Breast Cancer Treatment.

OBJECTIVES: To explore associations between quantitative sensory testing (QST) and pretreatment pain, physical, and psychological characteristics in women with breast cancer. SAMPLE & SETTING: 41 women with treatment-naive stage 0-III breast cancer at the University of Michigan Comprehensive Cancer Center in Ann Arbor. METHODS & VARIABLES: Participants completed self-report surveys and QST within the month before breast surgery. Pressure pain thresholds (PPTs) were measured bilaterally at each trapezius with a manual QST algometer. PPT values were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup self-reported characteristics were compared using Spearman's correlation, chi-square, and one-way analysis of variance. RESULTS: Lower PPT (higher sensitivity) was associated with higher levels of pain interference and maladaptive pain cognitions. The high-sensitivity group reported higher pain severities, interference, and catastrophizing and lower belief in internal locus of pain control than the low-sensitivity group. IMPLICATIONS FOR NURSING: Individualized interventions for maladaptive pain cognitions before surgery may reduce pain sensitivity and the severity of chronic pain developed after surgery.

Pressure Pain Sensitivity and Insular Combined Glutamate and Glutamine (Glx) Are Associated with Subsequent Clinical Response to Sham But Not Traditional Acupuncture in Patients Who Have Chronic Pain.

BACKGROUND: Clinical trials of acupuncture in chronic pain have largely failed to demonstrate efficacy of traditional over sham acupuncture. However, it should be noted that sham acupuncture is not inert. OBJECTIVE: To determine if experimental-pressure pain assessment and chemical neuroimaging can identify differential responsiveness to sham as opposed to traditional acupuncture. PATIENTS AND INTERVENTION: Fifty patients with fibromyalgia were randomized to either 9 traditional (TA) or sham (SA) acupuncture treatments over a period of 4 weeks. Both participants and assessors were blinded. MAIN OUTCOME MEASURES: The main outcome measures were pressure-pain sensitivity at the thumbnail, insular glutamate+glutamine (Glx), and clinical pain. RESULTS: PATIENTS WITH LOW PAIN SENSITIVITY (LPS), BUT NOT WITH HIGH PAIN SENSITIVITY (HPS), HAD A SIGNIFICANTLY REDUCED CLINICAL PAIN RESPONSE TO SA (CHANGE IN MEAN [STANDARD DEVIATION (SD)]: HPS -8.65 [7.91]; LPS -2.14 [6.68]; p=0.03). This relationship was not the case for TA (HPS -6.90 [4.51]; LPS -6.41 [9.25]; p=0.88). SA-treated patients who were more sensitive also had greater baseline levels of insular Glx than patients who were less sensitive (Glx mean [SD]: HPS 11.3 [1.18]; LPS 10.2 [0.54]; p=0.04). CONCLUSIONS: Pressure-pain testing may identify patients who are less likely to respond to SA. This effect may relate to the levels of brain excitatory neurotransmitters.