Auricular Point Acupressure to Manage Chemotherapy Induced Neuropathy

Brief Pain Inventory (BPI) assesses worst pain severity. The scale ranges from 0 (no pain) to 10 (severe pain), a higher score indicates greater pain

Brief Pain Inventory (BPI) assesses worst numbness. The scale ranges from 0 (no numbness) to 10 (severe numbness), a higher score indicates greater numbness.

Brief Pain Inventory (BPI) assesses worst Tingling. The scale ranges from 0 (no tingling) to 10 (severe tingling), a higher score indicates greater tingling.

Brief Pain Inventory (BPI) assesses worst stiffness. The scale ranges from 0 (no stiffness) to 10 (severe stiffness), a higher score indicates greater stiffness.

Peripheral motor neuropathy is graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Severity is graded on a scale that ranges from 1 to 5, with higher grade indicating greater severity of neuropathy.

Peripheral sensory neuropathy is graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Severity is graded on a scale that ranges from 1 to 5, with higher grade indicating greater severity of neuropathy.

The BPI-CIN Interference subscale will be used to measure physical function caused by CIN. The seven items evaluate interference with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life. Each item is rated on a 0-10 numeric scale (0 = does not interfere; 10 = completely interferes). The overall score is calculated as the mean of the seven items with a total score ranging from 0 to 10 to determine the level of interference, with higher scores indicating greater interference.

The ECOG Performance Status Scale describes level of functioning in terms of ability to care for oneself, daily activity, and physical. Score on the ECOG ranges from 0 (fully active and able) to 5 (dead) with higher score indicating lower function:

0 - Fully active, able to carry on all pre-disease performance without restriction

• - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
• - Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
• - Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
• - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
• - Dead

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - physical function subscale assesses physical function using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate better physical function.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - fatigue subscale assesses fatigue using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate greater fatigue.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - pain interference subscale assesses how pain interferes with daily activities using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate greater pain interference.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - depression subscale assesses depression using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate greater depression severity.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - anxiety subscale assesses anxiety using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate greater anxiety.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - sleep disturbance subscale assesses sleep disturbance using 4 items, each scored on a 5-point Likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate greater sleep disturbance.

Patient-Reported Outcomes Measurement Information System (PROMIS) 29 - ability to participate in social activities subscale assesses a participant's perceived ability to engage in usual social roles and activities using 4 items, each scored on a 5-point likert scale (1 = Unable to do; 5 = Without any difficulty). Raw scores ranging from 4 to 20 are converted to standardized T-scores (population mean = 50, Standard deviation = 10) using HealthMeasures tables with a range of approximately 20-80. The higher T-scores indicate better and higher functioning social participation.

The QuickDASH Index assesses upper limb disability and symptoms. It evaluates limitations in daily activities (e.g., opening jars, performing housework), as well as pain, tingling, and sleep disturbances. The total score ranges from 0 (no disability) to 100 (most severe disability), with higher scores indicating greater disability.

The MD Anderson Sympton Severity Inventory assesses severity of 13 common symptoms experienced by patients with cancer. Each item is rated on a 0-10 numeric scale (0 = not present; 10 = as bad as you can imagine). The overall symptom severity score is calculated as the mean of the 13 items with a range of 0 to 10, higher scores indicating greater symptom severity.

Pain self-efficacy is assessed using the Pain Self-Efficacy Questionnaire (PSEQ). This 10-item instrument measures a participant's confidence in performing daily activities, social life and function despite pain. Each item is rated on a 0-6 scale (0 = Not at all confident; 6 = Completely confident) and total score ranges from 0 to 60, with higher scores indicating greater self-efficacy and greater confidence in coping.

The Pain Catastrophizing Scale (PCS) assesses components of catastrophizing: rumination, magnification, and helplessness. The total score ranges from 0 to 52, with higher scores indicating greater pain catastrophizing.

Chronic Overlapping Pain Conditions (COPC) are assessed using the Chronic Overlapping Pain Conditions Screener (COPCS). This instrument identifies the presence of up to 10 common chronic pain conditions. The COPC total score is calculated as the number of positively identified conditions (answered "Yes"), with higher scores indicating greater pain impact, central sensitization, and severity.

The Charlson Comorbidity index assesses a participant's comorbidity burden and predicted risk of mortality. The total score ranges from 0 to 37. A higher score indicates greater comorbidity burden and higher risk of mortality.

Pain, Enjoyment and General Activity (PEG) is a three-item questionnaire that assesses pain intensity and its impact patient's daily life. Each item is rated on a 0-10 scale. The PEG score is calculated as the mean of three items, resulting in score range of 0 to 10, with a higher scores indicating greater pain severity and functional interference.

Opioid use will be collected via EMA diary using a questionnaire. Milligram Morphine Equivalent (MME) will be determined by using an equivalency factor to calculate a dose of morphine equivalent to the ordered opioid. Daily morphine equivalent dosing is sum of the MME of all opioids a patient is likely to take within 24 hours, and will be calculated to MME for analysis. Baseline was defined as the first day of opioid use recorded in the EMA diary.

In order to measure experimental pain sensitivity, a multimodal Quantitative Sensory Testing (QST) battery will be completed: pressure pain threshold (PPT), Mechanical Temporal Summation (MTS), and Conditioned Pain Modulation (CPM). To assess PPT, a handheld digital pressure algometer (Wagner, Greenwich, CT) was applied at a constant rate of 2.9 Newton per centimeter squared (N/cm^2) per second to the participant's trapezius and thumbs. Participants were asked to notify the experimenter when the pressure sensation ''first becomes painful." The pressure at which participants indicated that the pressure sensation ''first becomes painful" is reported.

In order to measure experimental pain sensitivity, a multimodal Quantitative Sensory Testing (QST) battery will be completed: pressure pain threshold (PPT), Mechanical Temporal Summation (MTS), and Conditioned Pain Modulation (CPM). To assess PPT, a handheld digital pressure algometer (Wagner, Greenwich, CT) was applied at a constant rate of 2.9 Newton per centimeter squared (N/cm^2) per second to the participant's trapezius and thumbs. Participants were asked to notify the experimenter when the pressure sensation ''first becomes painful." The pressure at which participants indicated that the pressure sensation ''first becomes painful" is reported.

In order to measure experimental pain sensitivity, a multimodal Quantitative Sensory Testing (QST) battery will be completed: pressure pain threshold (PPT), Mechanical Temporal Summation (MTS), and Conditioned Pain Modulation (CPM). To assess MTS, a single pinprick stimulus (e.g., via a weighted pinprick stimulator or Neuropen) is applied, followed by a series of 10 rapid, identical stimuli at the same location, usually at a rate of 1/second, to measure the change in pain sensation. Participants rate their pain after the stimuli using a Numeric Rating Scale (NRS) ranging from 0 to 10, where 0 = no pain and 10 = worst pain imaginable. A higher score means greater pain sensitivity and increased temporal summation. MTS is calculated as the increase in pain intensity rating (Δ change score) between the first stimulus and the end of the series.

In order to measure experimental pain sensitivity, a multimodal Quantitative Sensory Testing (QST) battery will be completed: pressure pain threshold (PPT), Mechanical Temporal Summation (MTS), and Conditioned Pain Modulation (CPM). CPM was assessed as the change in PPT on the trapezius immediately after the immersion of the contralateral hand up to the wrist in a cold-water bath (Neslab, Portsmouth, NH) at 4 degrees Celsius for 20 seconds. [ [To assess PPT, a handheld digital pressure algometer (Wagner, Greenwich, CT) was applied at a constant rate of 2.9 Newton per centimeter squared (N/cm^2) per second to the participant's trapezius. Participants were asked to notify the experimenter when the pressure sensation ''first becomes painful" to assess pressure pain threshold (PPT).]

Functional Magnetic Resonance Imaging (fMRI) will be used to assess changes in functional connectivity between the Salience Network and Basal Ganglia Network (SAL-BGN) from baseline to post-intervention (1 month after baseline). Functional connectivity is calculated based on the correlations in Blood Oxygen Level Dependent (BOLD) signal fluctuations in different brain regions. Connectivity strength will be quantified using Fisher z-transformed correlation coefficients, with higher values indicating stronger functional connectivity.

Functional Magnetic Resonance Imaging (fMRI) will be used to assess changes in functional connectivity between the Salience Network and Basal Ganglia Network (SAL-BGN) from baseline to post-intervention (1 month after baseline). Functional connectivity is calculated based on the correlations in Blood Oxygen Level Dependent (BOLD) signal fluctuations in different brain regions. Connectivity strength will be quantified using Fisher z-transformed correlation coefficients, with higher values indicating stronger functional connectivity.

The Grooved Pegboard Test assesses fine motor skills, speed, and visual-motor coordination. Participants are asked to place 25 pegs into slots as quickly as possible. The total time to complete the task is recorded in seconds with dominant hand. Higher times indicate slower performance and reduced dexterity

The Grooved Pegboard Test assesses fine motor skills, speed, and visual-motor coordination. Participants are asked to place 25 pegs into slots as quickly as possible. The total time to complete the task is recorded in seconds with non-dominant hand. Higher times indicate slower performance and reduced dexterity

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines (including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 (p40 and p70), IL-13, IL-17, IFN-γ, TNF-α, TGF-β) were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.

Blood samples were collected to measure cytokines and inflammatory biomarkers. Serum concentrations of cytokines and chemokines were quantified using a multiplex bead-based immunoassay. Biomarker concentrations were analyzed as indicators of inflammatory response at baseline and 1 month after baseline.