Stability of CPM in Two Musculoskeletal Pain Models
Stability of CPM in Two Musculoskeletal Pain Models
The University of Florida's institutional review board for human participants approved this study. This prospective design was part of a larger study and includes two groups of participants, a clinical cohort of patients having shoulder surgery, and a healthy cohort. All participants provided informed consent before participating in this study.
Clinical Cohort (Clinical Pain Model). This study includes data from consecutive patients seeking treatment of shoulder disorder, which were recruited from University of Florida's Orthopedics Sports Medicine Institute (OSMI). The inclusion criteria for being a participant in the clinical cohort were: patient between 18 and 85 years of age, complaints of pain limited to anterior, lateral, or posterior shoulder, rotator cuff tendinopathy, adhesive capsulitis, SLAP (Superior Labrum from Anterior to Posterior) lesion, and scheduled for arthroscopic surgery. Exclusion criteria for the prospective clinical cohort were: current complaints of pain greater than the past 3 months involving neck, elbow, hand, low back, hip, knee, or ankle, massive or complete rotator cuff tear, shoulder OA or RA, prior shoulder surgery within the past year, current shoulder fracture, tumor, or infection, previously diagnosed chronic pain disorder, current psychiatric management, and gastrointestinal or renal illness.
Healthy Cohort (Acute Pain Model). Healthy volunteers were recruited via advertisements from the University and local community. The inclusion criteria for the healthy cohort were: healthy subjects (without any pain or psychological condition) between 18 and 85 years of age, and English speaking. The exclusion criteria were: history of neck or shoulder injury, sensory or motor impairment of the shoulder, regular or recent participation in high or low intensity upper-extremity weight training, or currently taking pain medication. These eligibility criteria have been used in our previous studies of exercise-induced shoulder pain.
Demographic Information. Study participants completed a standard intake information form. Demographic data collected at initial evaluation included gender, age, race, ethnicity, employment status, marital status, and educational level.
Conditioned Pain Modulation (CPM). Test Stimulus: Suprathreshold heat pain response (SHPR) was used as the test stimulus. Pathway Pain & Sensory Evaluation System (Medoc, Ramat Yishai, Israel), with a thermode of 2.5 cm surface area was used. Sequences of 5 consecutive heat pulses of < 1-second duration at interpulse intervals of 0.33 Hz were delivered to the thenar eminence of the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort, as previously described. The temperature used for the test stimulus was determined from a previous SHPR assessment (five minutes before CPM assessment). One series of five stimuli was applied at each of three different target temperatures (46°C, 48°C and 50°C), and the temperature that produced an average pain intensity score closest to 50 on a 0–100 visual analogue scale (VAS) was used for the test stimulus in the CPM protocol completed on that day. This process was repeated each day that CPM was assessed to determine the temperature necessary to evoke moderate pain during the test stimuli. Subjects verbally rated the intensity of each thermal pulse on a numerical rating scale from 0 = "no pain" to 100 = "the worst pain imaginable". We selected SHPR as the test stimulus because evidence suggests that CPM effects are largest for C-fiber mediated pain. For analyses purposes, this study used the "5th pain rating" which was the fifth pain rating from the fifth pulse of each trial, which is considered to represent a simple measure of SHPR assessment.
Conditioning Stimulus (Cold-pressor Pain): Subjects were instructed to immerse their surgical side hand (for the clinical cohort), and dominant hand (in healthy cohort) up to the wrist into a cold water bath for up to one minute. The water was maintained at a constant temperature of 8°C by a refrigerated water circulator, and was constantly circulated to prevent warming around the hand.
CPM Procedure: Participants from both cohorts underwent the CPM assessment with the application of the test stimulus (described above) on the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort. After 30 s from the last heat stimulus, subjects were instructed to immerse their contralateral hand up to the wrist into the cold water bath (conditioning stimulus). Thirty seconds after hand immersion, subjects were asked to rate the pain intensity (0–100) from the immersed hand, and were instructed to maintain their hand in the water bath for as long as they could tolerate for a maximum of one minute. One minute after the immersion of the hand, a new test stimulus was delivered on the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort. The protocol was created with consecutive stimuli (test stimulus, then conditioning stimulus, hand removed from water, and then test stimulus). This sequence of delivering the test stimuli, followed by the conditioning stimulus, and ending with re-delivering the test stimuli constituted the first CPM trial (CPM1). After a two-minute rest period, the CPM protocol was repeated in exactly the same manner for a second trial (CPM2).
Exercise Induced Muscle Pain (EIMP). Pain was induced in subjects from the healthy cohort with a shoulder fatigue procedure using a Kin-Com (Chattanooga, TN) isokinetic dynamometer. Upper extremity EIMP is considered a clinically relevant pain model since participants experience increased pain intensity, decreased range of motion, an inflammatory response, altered proprioception, and the use of self-care behaviors. Muscle soreness occurs within 24 hours following the shoulder fatigue procedure with maximal soreness typically lasting 48 hours from the time of the procedure. Subjects typically experience decreasing levels of muscle soreness three to five days post-shoulder fatigue protocol.
Maximum voluntary isometric contraction (MVIC) was determined by having the participants perform external rotation contractions with maximal effort while receiving verbal encouragement during the contractions. The MVIC was calculated by averaging the peak force from the middle 3 repetitions, a method with documented reliability from previous studies. After MVIC was calculated, participants completed eccentric/concentric external rotation repetitions to induce muscle fatigue. Previously established procedures were utilized to induce pain in this cohort, which is described in more detail in our previous studies.
Pain Intensity. These data were included to describe the effects of clinical pain (surgical cohort) and exercise-induced shoulder pain (healthy cohort) on CPM stability. Pain intensity in both cohorts was assessed with the Brief Pain Inventory (BPI) questionnaire, which includes a numerical rating scale (NRS) for pain intensity. Subjects from the clinical cohort (before and 3 months after surgery) and from the healthy cohort (after EIMP protocol) rated their pain intensity over three conditions, the present pain intensity, the worst pain intensity over the past 24 h, and the best pain intensity over the past 24 h. These 3 ratings were averaged for use in data analyses.
Patients from the clinical cohort had a baseline examination (baseline) to collect demographic data, shoulder pain intensity, and quantitative sensory testing 72 to 24 hours before the surgery. They were reassessed 3 months after the surgery (3 months). Subjects from the healthy cohort were scheduled to come to the testing facility on day 1, day 3, and day 5. On Day 1, subjects had a baseline examination to collect demographic data, shoulder pain intensity, and quantitative sensory testing (CPM and pain threshold) in a pain free state. Subjects completed strength testing, followed by eccentric/concentric external rotation repetitions to induce muscle fatigue. Collection of quantitative sensory testing and shoulder pain intensity was repeated on days 3 and 5 following EIMP induction.
Data analysis was performed in SPSS, Version 19.0 at alpha level of 0.05. Descriptive statistics (mean, standard deviation) were calculated for all variables. The distributions of variables were tested by visual examination and with Kolmogorov-Smirnov test before use in analysis.
Calculations for CPM. For analysis purposes on CPM, we followed recent recommendations on presenting results and calculation of CPM using the absolute difference for CPM and the percent change. The "absolute difference" for CPM, was calculated by the difference between test stimulus before the application of conditioning stimulus (pre CPM), minus the test stimulus after the application of conditioning stimulus (post CPM). The "percent change" for CPM was calculated as follows:
For each session there were two absolute difference and two percent change scores for CPM variables; one from the first CPM trial (CPM trial 1) and one from the second CPM trial (CPM trial 2). CPM trials were repeated before and 3 month after the surgery for the clinical cohort, and on three different days (Days 1, 3, and 5) for the healthy cohort.
Clinical Cohort. Stability analyses for CPM measures included intraclass correlations (ICC's) for the absolute difference of CPM and the percent change of CPM only within session (trial 1 and trial 2). These results were reported with the appropriate coefficient and 95% confidence interval (CI). From these data the standard error of measurement (SEM) was calculated for each measure using a previously described method [standard deviation*√(1 – test rest reliability coefficient)]. The minimal detectable change (MDC95) was calculated using a previously described method (1.96*SEM*√2). The stability estimates (SEM and MDC95) provide an idea of how much individual change is necessary before measurement error is likely to have been exceeded. To determine whether sex influences CPM stability, ICC's stratified by sex were also reported.
Repeated measures ANOVAs were used to assess the effect of trial (trial 1 and trial 2) on within session for the absolute difference of CPM. Next, shoulder pain intensity was included as a covariate to investigate the impact that pain intensity had on CPM stability. The analysis was performed separately for each session of the clinical cohort (session 1 and 3 months).
Healthy Cohort. Stability analyses for CPM measures included intraclass correlations (ICC's) for the absolute difference of CPM and the percent change of CPM within session (trial 1 and trial 2) and between sessions (day 1, day 3, and day 5). As in the clinical cohort, these results were reported with the appropriate 95% CI, SEM, and the MDC95. ICC's stratified by sex were also reported.
Repeated measures ANOVAs were used to assess the effect of trial (trial 1 and trial 2) on within session for the absolute difference of CPM. The analysis was performed separately for each session of the healthy cohort (day 1, day 3, and day 5). In addition, repeated measures ANOVA were used to assess the effect of time (day 1, day 3, and day 5) on the absolute difference of CPM with and without the inclusion of shoulder pain intensity as a covariate to investigate the impact that pain intensity had on CPM stability on between sessions.
Methods
Subjects
The University of Florida's institutional review board for human participants approved this study. This prospective design was part of a larger study and includes two groups of participants, a clinical cohort of patients having shoulder surgery, and a healthy cohort. All participants provided informed consent before participating in this study.
Clinical Cohort (Clinical Pain Model). This study includes data from consecutive patients seeking treatment of shoulder disorder, which were recruited from University of Florida's Orthopedics Sports Medicine Institute (OSMI). The inclusion criteria for being a participant in the clinical cohort were: patient between 18 and 85 years of age, complaints of pain limited to anterior, lateral, or posterior shoulder, rotator cuff tendinopathy, adhesive capsulitis, SLAP (Superior Labrum from Anterior to Posterior) lesion, and scheduled for arthroscopic surgery. Exclusion criteria for the prospective clinical cohort were: current complaints of pain greater than the past 3 months involving neck, elbow, hand, low back, hip, knee, or ankle, massive or complete rotator cuff tear, shoulder OA or RA, prior shoulder surgery within the past year, current shoulder fracture, tumor, or infection, previously diagnosed chronic pain disorder, current psychiatric management, and gastrointestinal or renal illness.
Healthy Cohort (Acute Pain Model). Healthy volunteers were recruited via advertisements from the University and local community. The inclusion criteria for the healthy cohort were: healthy subjects (without any pain or psychological condition) between 18 and 85 years of age, and English speaking. The exclusion criteria were: history of neck or shoulder injury, sensory or motor impairment of the shoulder, regular or recent participation in high or low intensity upper-extremity weight training, or currently taking pain medication. These eligibility criteria have been used in our previous studies of exercise-induced shoulder pain.
Measures and Procedure
Demographic Information. Study participants completed a standard intake information form. Demographic data collected at initial evaluation included gender, age, race, ethnicity, employment status, marital status, and educational level.
Conditioned Pain Modulation (CPM). Test Stimulus: Suprathreshold heat pain response (SHPR) was used as the test stimulus. Pathway Pain & Sensory Evaluation System (Medoc, Ramat Yishai, Israel), with a thermode of 2.5 cm surface area was used. Sequences of 5 consecutive heat pulses of < 1-second duration at interpulse intervals of 0.33 Hz were delivered to the thenar eminence of the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort, as previously described. The temperature used for the test stimulus was determined from a previous SHPR assessment (five minutes before CPM assessment). One series of five stimuli was applied at each of three different target temperatures (46°C, 48°C and 50°C), and the temperature that produced an average pain intensity score closest to 50 on a 0–100 visual analogue scale (VAS) was used for the test stimulus in the CPM protocol completed on that day. This process was repeated each day that CPM was assessed to determine the temperature necessary to evoke moderate pain during the test stimuli. Subjects verbally rated the intensity of each thermal pulse on a numerical rating scale from 0 = "no pain" to 100 = "the worst pain imaginable". We selected SHPR as the test stimulus because evidence suggests that CPM effects are largest for C-fiber mediated pain. For analyses purposes, this study used the "5th pain rating" which was the fifth pain rating from the fifth pulse of each trial, which is considered to represent a simple measure of SHPR assessment.
Conditioning Stimulus (Cold-pressor Pain): Subjects were instructed to immerse their surgical side hand (for the clinical cohort), and dominant hand (in healthy cohort) up to the wrist into a cold water bath for up to one minute. The water was maintained at a constant temperature of 8°C by a refrigerated water circulator, and was constantly circulated to prevent warming around the hand.
CPM Procedure: Participants from both cohorts underwent the CPM assessment with the application of the test stimulus (described above) on the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort. After 30 s from the last heat stimulus, subjects were instructed to immerse their contralateral hand up to the wrist into the cold water bath (conditioning stimulus). Thirty seconds after hand immersion, subjects were asked to rate the pain intensity (0–100) from the immersed hand, and were instructed to maintain their hand in the water bath for as long as they could tolerate for a maximum of one minute. One minute after the immersion of the hand, a new test stimulus was delivered on the non-surgical side for the clinical cohort, and non-dominant side for the healthy cohort. The protocol was created with consecutive stimuli (test stimulus, then conditioning stimulus, hand removed from water, and then test stimulus). This sequence of delivering the test stimuli, followed by the conditioning stimulus, and ending with re-delivering the test stimuli constituted the first CPM trial (CPM1). After a two-minute rest period, the CPM protocol was repeated in exactly the same manner for a second trial (CPM2).
Exercise Induced Muscle Pain (EIMP). Pain was induced in subjects from the healthy cohort with a shoulder fatigue procedure using a Kin-Com (Chattanooga, TN) isokinetic dynamometer. Upper extremity EIMP is considered a clinically relevant pain model since participants experience increased pain intensity, decreased range of motion, an inflammatory response, altered proprioception, and the use of self-care behaviors. Muscle soreness occurs within 24 hours following the shoulder fatigue procedure with maximal soreness typically lasting 48 hours from the time of the procedure. Subjects typically experience decreasing levels of muscle soreness three to five days post-shoulder fatigue protocol.
Maximum voluntary isometric contraction (MVIC) was determined by having the participants perform external rotation contractions with maximal effort while receiving verbal encouragement during the contractions. The MVIC was calculated by averaging the peak force from the middle 3 repetitions, a method with documented reliability from previous studies. After MVIC was calculated, participants completed eccentric/concentric external rotation repetitions to induce muscle fatigue. Previously established procedures were utilized to induce pain in this cohort, which is described in more detail in our previous studies.
Pain Intensity. These data were included to describe the effects of clinical pain (surgical cohort) and exercise-induced shoulder pain (healthy cohort) on CPM stability. Pain intensity in both cohorts was assessed with the Brief Pain Inventory (BPI) questionnaire, which includes a numerical rating scale (NRS) for pain intensity. Subjects from the clinical cohort (before and 3 months after surgery) and from the healthy cohort (after EIMP protocol) rated their pain intensity over three conditions, the present pain intensity, the worst pain intensity over the past 24 h, and the best pain intensity over the past 24 h. These 3 ratings were averaged for use in data analyses.
Testing Sequence
Patients from the clinical cohort had a baseline examination (baseline) to collect demographic data, shoulder pain intensity, and quantitative sensory testing 72 to 24 hours before the surgery. They were reassessed 3 months after the surgery (3 months). Subjects from the healthy cohort were scheduled to come to the testing facility on day 1, day 3, and day 5. On Day 1, subjects had a baseline examination to collect demographic data, shoulder pain intensity, and quantitative sensory testing (CPM and pain threshold) in a pain free state. Subjects completed strength testing, followed by eccentric/concentric external rotation repetitions to induce muscle fatigue. Collection of quantitative sensory testing and shoulder pain intensity was repeated on days 3 and 5 following EIMP induction.
Data Analysis
Data analysis was performed in SPSS, Version 19.0 at alpha level of 0.05. Descriptive statistics (mean, standard deviation) were calculated for all variables. The distributions of variables were tested by visual examination and with Kolmogorov-Smirnov test before use in analysis.
Calculations for CPM. For analysis purposes on CPM, we followed recent recommendations on presenting results and calculation of CPM using the absolute difference for CPM and the percent change. The "absolute difference" for CPM, was calculated by the difference between test stimulus before the application of conditioning stimulus (pre CPM), minus the test stimulus after the application of conditioning stimulus (post CPM). The "percent change" for CPM was calculated as follows:
For each session there were two absolute difference and two percent change scores for CPM variables; one from the first CPM trial (CPM trial 1) and one from the second CPM trial (CPM trial 2). CPM trials were repeated before and 3 month after the surgery for the clinical cohort, and on three different days (Days 1, 3, and 5) for the healthy cohort.
Clinical Cohort. Stability analyses for CPM measures included intraclass correlations (ICC's) for the absolute difference of CPM and the percent change of CPM only within session (trial 1 and trial 2). These results were reported with the appropriate coefficient and 95% confidence interval (CI). From these data the standard error of measurement (SEM) was calculated for each measure using a previously described method [standard deviation*√(1 – test rest reliability coefficient)]. The minimal detectable change (MDC95) was calculated using a previously described method (1.96*SEM*√2). The stability estimates (SEM and MDC95) provide an idea of how much individual change is necessary before measurement error is likely to have been exceeded. To determine whether sex influences CPM stability, ICC's stratified by sex were also reported.
Repeated measures ANOVAs were used to assess the effect of trial (trial 1 and trial 2) on within session for the absolute difference of CPM. Next, shoulder pain intensity was included as a covariate to investigate the impact that pain intensity had on CPM stability. The analysis was performed separately for each session of the clinical cohort (session 1 and 3 months).
Healthy Cohort. Stability analyses for CPM measures included intraclass correlations (ICC's) for the absolute difference of CPM and the percent change of CPM within session (trial 1 and trial 2) and between sessions (day 1, day 3, and day 5). As in the clinical cohort, these results were reported with the appropriate 95% CI, SEM, and the MDC95. ICC's stratified by sex were also reported.
Repeated measures ANOVAs were used to assess the effect of trial (trial 1 and trial 2) on within session for the absolute difference of CPM. The analysis was performed separately for each session of the healthy cohort (day 1, day 3, and day 5). In addition, repeated measures ANOVA were used to assess the effect of time (day 1, day 3, and day 5) on the absolute difference of CPM with and without the inclusion of shoulder pain intensity as a covariate to investigate the impact that pain intensity had on CPM stability on between sessions.
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