Comparative sensitivity of stopwatch methodology and conventional pain assessment measures for detecting early response to triptans in migraine: results of a randomized, open-label pilot study

BACKGROUND: The standard measure of efficacy used in migraine trials is a 4-point patient-rated headache pain intensity (HPI) scale. However, it has been suggested that using a stopwatch to measure the time to meaningful pain relief can provide a more precise measurement of treatment response. OBJECTIVE: This study evaluated the sensitivity of a stopwatch method for detecting meaningful relief of headache pain and the correlation of this method with the HPI scale and a 5-point pain relief scale. METHODS: In this open-label, parallel-group pilot study, patients were randomized to receive oral eletriptan 40 mg, eletriptan 80 mg, or rizatriptan 10 mg for the treatment of a single acute migraine attack. The effect of study treatment on migraine pain was assessed immediately before dosing and at 0.5, 1, 1.5, 2, 3, and 4 hours after dosing. At each time point, patients recorded the 3 types of pain assessment in a patient diary. HPI was rated using the standard 4-point International Headache Society pain intensity scale (from 0 = no pain to 3 = severe pain). Pain relief was rated on a 5-point pain relief scale (from 4 = no relief to 0 = complete relief). The time to the onset of meaningful pain relief was measured using a stopwatch. At 4 hours after dosing, patients provided a global rating of the overall efficacy of study medication on a 5-point scale (from 0 = poor to 4 = excellent). RESULTS: Seventy-nine patients participated in the trial (78.5% female; mean [SD] age, 37.7 [9.8] years; 58.2% white). The median times to meaningful pain relief measured by stopwatch were 84, 72, and 93 minutes for eletriptan 40 mg, eletriptan 80 mg, and rizatriptan 10 mg, respectively (log-rank P = 0.029, eletriptan 80 mg vs rizatriptan 10 mg). At 90 minutes (approximating the median time to meaningful pain relief on the stopwatch), headache response rates using HPI scoring (mild to no pain) were 65%, 68%, and 52% in the respective treatment groups, with no significant difference between groups. On the pain relief scale, the corresponding mean (SD) scores at 90 minutes were 1.6 (1.2), 1.4 (1.3), and 2.0 (1.4) (P = NS). The pain relief-defined response (> or = 75% pain relief) at 90 minutes did not differ significantly between the 3 treatment groups (62%, 56%, and 48%). Detection of early improvement (0.5 and 1 hour) was similar with the HPI and pain relief scales. CONCLUSION: The results of this open-label pilot study suggest the convergent validity of 3 pain-assessment methods in migraine, but indicate that the use of a stopwatch may be a more sensitive method for detecting between-group differences.     

Sensitivity of pain rating scales in an endoscopy trial

OBJECTIVE: The purpose of this study was to compare the sensitivity of two commonly used pain-rating scales, the Visual Analog Scale and the 4-point verbal rating scale. Both are considered reliable and valid, but previous studies regarding sensitivity of rating scales have lead to different conclusions, and there is no firm agreement as to the best scale to choose. METHODS: The sensitivity of the Visual Analog Scale and the 4-point verbal rating scale was compared by stochastic simulation. In the simulation model, we used 168 pairs of pain ratings on the Visual Analog Scale and the 4-point verbal rating scale from individuals undergoing a lower gastrointestinal endoscopy, maintaining the true relation between ratings from the same individual. We created empirical distributions mimicking 2 independent groups of pain ratings. Random samples from the 2 groups were compared by the Wilcoxon-Mann-Whitney U test in 10,000 repetitions of a computer algorithm. By increasing the proportion of individuals with a high level of pain in one group, we increased the true difference between pain ratings and estimated a statistical power function. RESULTS: In the present pain model with pain ratings from healthy individuals undergoing endoscopy, the Visual Analog Scale is consistently more sensitive than the four-point verbal rating scale. DISCUSSION: Because each individual provided one Visual Analog Scale and one 4-point verbal rating scale rating for the same pain experience, the ability of the two scales to detect differences between groups of pain ratings could be compared. The use of a simulation model enabled estimation of a power function and reduced the probability of basing the conclusion on a chance finding.     

A comparison of pain rating scales by sampling from clinical trial data

OBJECTIVE: The goals of this study were to examine agreement and estimate differences in sensitivity between pain assessment scales. DESIGN: Multiple simultaneous pain assessments by patients in acute pain after oral surgery were used to compare a four-category verbal rating scale (VRS-4) and an 11-point numeric rating scale (NRS-11) with a 100-mm visual analog scale (VAS). The sensitivity of the scales (i.e., their ability [power] to detect differences between treatments) was compared in a simulation model by sampling from true pairs of observations using varying treatment differences of predetermined size. RESULTS: There was considerable variability in VAS scores within each VRS-4 or NRS-11 category both between patients and for repeated measures from the same patient. Simulation experiments showed that the VAS was systematically more powerful than the VRS-4 in all simulations performed. The sensitivity of the VAS and NRS-11 was approximately equal. CONCLUSIONS: In this acute pain model, the VRS-4 was less sensitive than the VAS. The simulation results demonstrated similar sensitivity of the NRS-11 and VAS when comparing acute postoperative pain intensity. The choice between the VAS and NRS-11 can thus be based on subjective preferences.     

Response measures in the acute treatment of migraine

Pain ratings from 268 migraine patients have been used to compare the visual analogue scale (VAS) and a four-point verbal rating scale. All patients completed pain ratings on both scales at the beginning of a migraine attack and 4 h after starting treatment with sumatriptan or placebo. The VAS scores showed large variability within each category on the verbal rating scale. A common way of analysing pain in migraine studies is to classify patient response as a success or failure based on the score on the four-point verbal rating scale. In this study, the statistical power of analysing response either as "success or failure" or by means of the VAS score has been investigated by stochastic simulation. The simulations showed that the two response measures resulted in approximately equal power.     

Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.

Pain intensity is frequently measured on an 11-point pain intensity numerical rating scale (PI-NRS), where 0=no pain and 10=worst possible pain. However, it is difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1- or 2-point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies. We have estimated a clinically important difference on this scale by relating it to global assessments of change in multiple studies of chronic pain. Data on 2724 subjects from 10 recently completed placebo-controlled clinical trials of pregabalin in diabetic neuropathy, postherpetic neuralgia, chronic low back pain, fibromyalgia, and osteoarthritis were used. The studies had similar designs and measurement instruments, including the PI-NRS, collected in a daily diary, and the standard seven-point patient global impression of change (PGIC), collected at the endpoint. The changes in the PI-NRS from baseline to the endpoint were compared to the PGIC for each subject. Categories of "much improved" and "very much improved" were used as determinants of a clinically important difference and the relationship to the PI-NRS was explored using graphs, box plots, and sensitivity/specificity analyses. A consistent relationship between the change in PI-NRS and the PGIC was demonstrated regardless of study, disease type, age, sex, study result, or treatment group. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI-NRS represented a clinically important difference. The relationship between percent change and the PGIC was also consistent regardless of baseline pain, while higher baseline scores required larger raw changes to represent a clinically important difference. The application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies.     

Migraine with aura versus migraine without aura: pain intensity and associated symptom intensities after placebo

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo administration in patients with migraine with aura and migraine without aura. BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine ideally should include a placebo arm. The International Headache Society also recommends stratification according to age and sex but not by the presence versus absence of aura. METHODS: The study was conducted as part of a placebo controlled randomized survey comparing four active drugs against placebo in the acute treatment of migraine. Patients were blinded as to treatment received. Placebo consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and phonophobia were evaluated by a four-point analogical-verbal scale. For statistical analysis, unpaired t-test with Welch correction was used. RESULTS: After placebo administration, reduction of symptom intensity (pain, nausea, photophobia, and phonophobia) in patients with migraine without aura was significantly greater than that observed in patients with migraine with aura. CONCLUSIONS: Our findings suggest that studies comparing placebo against an active drug should use stratification according to the presence versus absence of aura.     

Likert pain score modeling: a Markov integer model and an autoregressive continuous model

Pain intensity is principally assessed using rating scales such as the 11-point Likert scale. In general, frequent pain assessments are serially correlated and underdispersed. The aim of this investigation was to develop population models adapted to fit the 11-point pain scale. Daily Likert scores were recorded over 18 weeks by 231 patients with neuropathic pain from a clinical trial placebo group. An integer model consisting of a truncated generalized Poisson (GP) distribution with Markovian transition probability inflation was implemented in NONMEM 7.1.0. It was compared to a logit-transformed autoregressive continuous model with correlated residual errors. In both models, the score baseline was estimated to be 6.2 and the placebo effect to be 19%. Developed models similarly retrieved consistent underlying features of the data and therefore correspond to platform models for drug effect detection. The integer model was complex but flexible, whereas the continuous model can more easily be developed, although requires longer runtimes.     

Comparing patients' and their physicians' assessments of pain

Patients and their physicians were asked to estimate the pain from needle aspiration and/or injection of joints or soft tissue using the visual analogue scale. On a 10-point scale, the mean score for patients prior to and after the procedure was 4.76 +/- 2.97 and 4.01 +/- 3.51, respectively, and for physicians was 4.15 +/- 2.45 and 3.36 +/- 2.08. Analysis of correlations revealed that prior to the procedure patients could predict their 'true' pain (after the procedure assessment) better (r = 0.765) than physicians could predict patients' pain (r = 0.542). However, physicians significantly improved their estimates of patients' scores by observing the procedure. After the procedure correlation between physician and patient scores increased to 0.62 (P = 0.003). The overall pattern of results suggests that experienced patients may be somewhat better than their physicians in predicting the level of pain they experience with a procedure, but that physicians' estimates appear to be accurate enough to allow them to give useful information about the degree of discomfort that a patient will experience during an invasive procedure.     

The effect of manipulation on pain and range of motion in the cervical spine: a pilot study.

OBJECTIVE: The objective of this pilot study was to determine the number of patients required for a randomized controlled trial of spinal manipulation for neck pain and to determine if there is a relationship between pain and range of motion (ROM) in the cervical spine. DESIGN: Fifty consecutive outpatients were studied in a pretest-posttest design without long-term follow-up. SETTING: The patients were taken from a primary cae outpatient teaching clinic specializing in back pain. PATIENTS: All patients had unilateral neck pain without neurological deficit. The patients were selected as a consecutive sample. INTERVENTION: All the patients received a single cervical manipulation. MAIN OUTCOME MEASURES: Prior to and immediately after the treatment, cervical ROM was recorded on a goniometer, and pain intensity was rated on the 101-point numerical rating scale. RESULTS: The results show an increase in all planes of post-treatment ROM and a decrease in post-treatment pain scores. Partial correlations between post-treatment ROM and 101-point numerical rating scale scores reveal a significant relationship between a decrease in pain and an increase in cervical rotation (p < .005). CONCLUSIONS: Since the results of this pilot study are not controlled, they cannot be seen as proof supporting the clinical efficacy of manipulation for neck pain. However, the correlation between an increase in cervical rotation and a decrease in pain is clinically instructive. In addition, the outcome measures used in this study could prove to be useful in the design of future randomized controlled trials of cervical manipulation.     

The effects of greater occipital nerve block and trigger point injection on brush allodynia and pain in migraine

OBJECTIVE: To evaluate the effect of GONB, with or without trigger point injection (TPI), on dynamic mechanical (brush) allodynia (BA) and on head pain in migraine. Background.-Patients with migraine often have cutaneous allodynia that is related to sensitization of central pain neurons. Greater occipital nerve block (GONB) is an effective treatment for migraine headache; however, its effect on cutaneous allodynia in migraine is unknown. METHODS: We studied patients with migraine and BA who were treated with GONB with or without TPI. Demographic data, migraine history, and headache features were documented. Allodynia was evaluated using a structured questionnaire and by applying a 4 x 4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia (the allodynia score) was measured on a 100-mm visual analog scale (VAS) before treatment and 10 and 20 minutes thereafter. Headache levels were assessed using an 11-point verbal scale. Allodynia scores, as well as headache levels, before and after treatment were compared. RESULTS: Nineteen patients were studied. Mean age was 43.6+/-11.8 years. Twenty minutes after treatment, headache was reduced in 17 patients (89.5%) and did not change in 2 (10.5%). The average headache level was 6.53 before treatment and 3.47, 20 minutes after it. The average allodynia score decreased after 20 minutes in all patients. Average allodynia score per site was reduced by 18.69 mm and 13.74 mm in the trigeminal and cervical areas, respectively. There was a positive correlation between allodynia index, obtained through the questionnaire, and allodynia score, obtained by examination. CONCLUSION: GONB, with or without TPI, reduced both head pain and brush allodynia in this migraine patient group.     

Back Performance Scale for the assessment of mobility-related activities in people with back pain

BACKGROUND AND PURPOSE: Activities that require mobility of the trunk are often limited in patients with back problems. For this study, 5 tests (Sock Test, Pick-up Test, Roll-up Test, Fingertip-to-Floor Test, and Lift Test), all requiring sagittal-plane mobility, were performed, and the test scores were combined by the authors in a scale called the Back Performance Scale (BPS) to obtain a performance measure of mobility-related activities. SUBJECTS: The participants were 288 patients with long-lasting musculoskeletal pain. METHODS: The basis for constructing a sum scale (BPS), discriminative ability, and responsiveness to important change of the BPS were examined in patients with back pain. RESULTS: Bivariate correlations (rs) of scores among tests ranged from.27 to.50, and correlations between separate tests and the BPS ranged from.63 to.73. The Cronbach alpha was.73. The BPS sum scores discriminated between patients with different return to work status and were higher for back pain than for other musculoskeletal pain. Responsiveness was high (effect size=1.33) in patients who had changed and low (effect size=0.31) in patients who had not changed, using return to work as an external indicator of important change. The BPS was more responsive than the separate tests. DISCUSSION AND CONCLUSION: The BPS appears to measure an aspect of physical performance that is of clinical importance to patients with back pain.     

MMPI patterns in chronic muscle pain, tension headache and migraine

MMPI personality profiles were obtained from three clinical groups (n = 79). One group consisted of men and women with chronic muscle pain (MP; n = 34), a second group of male and female chronic tension headache patients (TH; n = 12), and a third group of female migraine patients (M; n = 33). The M group was subdivided on the basis of source of referral and into groups of classic versus common migraine. Elevation of the MMPI subscales usually interpreted as neuroticism scales were found in all groups. A "psychosomatic V" pattern was found on these scales in the M group but not in female TH patients. The difference in scale configuration between groups was caused primarily by different elevations on the depression scale. A relationship between severity of headache and elevation of the "psychosomatic V" was found in migraine patients. Male MP and TH patients showed a descending slope on the neuroticism scales, not observed in females. There was a tendency for common migraine patients to show a more elevated and psychosomatic configuration on the MMPI, as compared with classic migraine patients.     

The cognitive risk profile for pain: development of a self-report inventory for identifying beliefs and attitudes that interfere with pain management

OBJECTIVES: An extensive body of research suggests that maladaptive beliefs about chronic pain can have a negative impact on patient adherence and treatment response. A series of studies to develop and validate a clinically-based, self-report instrument for pain beliefs, the Cognitive Risk Profile for Pain (CRPP), was undertaken. We sought to expand the existing body of knowledge for pain beliefs by development of an instrument with a somewhat different content and format than prior pain belief measures, and a primary focus on clinical risk assessment for treatment planning. METHODS: Test development and evaluation procedures were applied in the initial stages of CRPP development. We report here on a series of studies to evaluate and refine the structure and content of the CRPP, and to establish its internal reliability, concurrent, and criterion validities. A 68-item version of the CRPP was evaluated, including a total risk score and 9 scale scores: philosophic beliefs about pain (PB), denial that mood affects pain (MP), denial that pain affects mood (PM), perception of blame (BL), inadequate support (IS), disability entitlement (DE), desire for medical breakthrough (MB), skepticism of multidisciplinary approach (SM), and conviction of hopelessness (CH). The CRPP was administered to two large samples of chronic pain outpatients (n=499; 125) in conjunction with other self-report scales for pain and associated beliefs, behaviors, and psychopathology. In a final study, treatment outcome measures were obtained for a subsample of chronic pain patients (n=91) to evaluate criterion validity. RESULTS: Confirmatory factor analyses showed improved fit for the CRPP scale structure after elimination of 15 items. The resulting 53-item CRPP was found to have good internal consistency for the full score (alpha=0.82) and 7 of 9 scales, with moderate consistency for scales BL and MB. Low to moderate scale intercorrelations were found. Correlations with pain and psychosocial measures suggested good construct validity for the majority of individual scales and total score. Results were inconsistent for scale MP. Multivariate analyses of variances (MANOVAs) based on tertile split of total risk scores showed significant main effects across pain, mood, productivity, and sleep ratings at 3 and 6-month treatment follow-ups. Analyses of clinically significant treatment changes (ie, 2 points on a 11-point Numerical Rating Scales) showed significantly higher prevalence of treatment "failures" at 6 months among CRPP high-risk patients, but no significant differences at 3 months. DISCUSSION: Results provide initial support for the CRPP as a reliable, valid, and useful measure of general cognitive risk for pain management. Results were supportive of the content and reliabilities of the majority of scale scores. Scales for denial of mood impact on pain, perception of blame, and desire for medical breakthrough will require further evaluation. Data indicate an association of CRPP total risk with multidimensional outcome from medical treatment of chronic pain, supporting relevance to treatment planning. The unique content and format of the CRPP may be useful in some clinical pain settings. Possible applications of the CRPP for risk assessment and treatment planning for chronic pain are discussed.     

Estimation of pain intensity in emergency medicine: a validation study

This study was designed to estimate the validity of an 11-point verbal numerical rating scale (VNRS) and a 100 Unit (U) plasticized visual analogue scale (VASp) using a 100mm paper visual analogue scale (VAS) as a gold standard, to recommend the best method of reporting the intensity of acute pain in an emergency department (ED). A convenience sample of 1176 patients with acute pain were recruited in the ED of a teaching hospital. Patients >18 years and able to use the different scales were included. Scales were presented randomly. Results were converted to a 0-100 U scale and validity was quantified using the Bland-Altman method and the intra-class correlation (ICC). The limits of acceptability were previously set for the limits of agreement at +/-20 U, with a constant bias. The Bland-Altman method revealed a small bias of -4 U for the VNRS and +1 U for VASp. However, the bias of the VNRS varied with the intensity of pain from -10 to +1 U. The limits of agreement between the VNRS&VAS and the VASp&VAS were -25; +17 U and -17; +18 U, respectively. The ICC was excellent between the VNRS&VAS (0.88) and the VASp&VAS (0.92). In conclusion, the VASp has a small bias, acceptable limits of agreement and an excellent intra-class correlation. It is probably a valid tool to estimate acute pain in the ED. However, the VNRS is less valid in that context because of its wide limits of agreement and variable bias (mainly in lower scores).     

A clinical comparison of two pain scales: correlation, remembering chronic pain, and a measure of compliance

Fifteen chronic pain patients rated their pain intensity on both a visual analogue scale and a verbal scale so that comparisons between the scales could be made for each subject. Compliance to fill in the rating blanks and the remembering of pain intensity were also studied. Subjects first made a pre-baseline estimate of their pain and then they rated their pain throughout a baseline and treatment period averaging 5 weeks. Four to 9 weeks after baseline, subjects were asked to remember how much pain they had had at baseline and to confidentially provide ratings concerning their compliance. Results indicated that two-thirds of the individual subjects had significant correlations between the scales with a mean of 0.68. The one-third of the subjects who did not have significant correlations also had significantly less variability in their ratings than did subjects with significant correlations. This low level of variability may account for the lack of a significant correlation between the scales for these subjects. Discrepancies between actual baseline and remembered pain ratings were observed on both rating scales, but the visual analogue scale produced significantly greater discrepancies than the verbal scale. This was mainly because subjects tended to overestimate their baseline pain on the visual analogue scale, while discrepancies on the verbal scale were in both directions (overestimations, underestimations) when taken as a group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in outpatients: a case series

BACKGROUND: Migraine headache pain that does not respond to traditional antimigraine medications frequently requires treatment in the emergency department (ED) with parenteral opioids. Rapid onset of pain relief in an outpatient setting for migraine headache is the primary objective of patients and clinicians. Oral transmucosal fentanyl citrate (OTFC; ACTIQ) is a novel opioid product designed to deliver rapid analgesia to patients who experience breakthrough pain (BTP). OBJECTIVE: To evaluate the effectiveness, tolerability, and patient satisfaction with OTFC for the outpatient treatment of acute, refractory migraine headache pain. PATIENTS AND METHODS: Twenty patients with recurrent acute, refractory migraine headaches who had been referred to this headache clinic are reported in this case series. All patients had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. Patients were prescribed OTFC (400 microg) as rescue treatment for moderate or severe migraine headache pain as outpatients. Patients were instructed to self-administer OTFC at home and complete a diary recording: pain intensity (11-point scale; 10 = worst pain imaginable to 0 = no pain) before and 15, 30, 60, and 120 minutes after OTFC; satisfaction with the effectiveness of OTFC (selecting 1 of 7 categories ranging from "very dissatisfied" through "very satisfied") rated at 120 minutes; and adverse events. RESULTS: Eighteen patients (13 female) experienced a migraine and self-administered OTFC. OTFC successfully treated migraine episodes in all 18 outpatients; no patient went to an ED. OTFC rapidly reduced pain intensity, with significant improvement at 15 minutes that was sustained and provided progressively more pain relief at 30, 60, and 120 minutes (all P <.01). Mean (SEM) pain intensity significantly declined from 8.83 (0.35) pretreatment to 2.28 (0.67) at 120 minutes, an average reduction of 75% (P <.01). Patients' satisfaction ratings with OTFC were overwhelmingly positive, with 94% being satisfied and more than half (56%) being "very satisfied." Three (17%) patients experienced nausea, two (11%) somnolence, and one (6%) each itching, vomiting, and dry mouth. All adverse events were mild or moderate in severity. CONCLUSIONS: OTFC rapidly and significantly relieved acute, refractory migraine pain in outpatients, prevented the need for an ED visit, and was associated with high patient satisfaction ratings. The rapid onset of migraine headache pain relief in this case series is consistent with the analgesic effect reported with the use of OTFC in patients with BTP. OTFC was well tolerated in these patients who had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. OTFC may be effective for outpatient treatment of acute, refractory migraine headache pain. Further controlled studies are warranted.     

Comparative study of methods of measuring acute pain intensity in an ED

The best one-dimensional method for routine self-assessment of acute pain intensity in a hospital emergency department is unknown. In this study, an 11-point numerical rating scale (NRS), a simple verbal rating scale describing five pain states (VRS), and a visual analogue scale (VAS) were presented successively on admission to 290 patients with acute pain (200 with and 90 without trauma). VAS and NRS were closely correlated for both traumatic (r = .795) and nontraumatic pain (r = .911). The VAS could not be used with 19.5% of patients with trauma and the VRS with 11% of patients without trauma, whereas the NRS could be used with 96% of all patients. The NRS proved more reliable for patients with trauma, giving equivalent results to those with the VAS for patients without trauma. These two scales showed better discriminant power for all patients. Thus, the NRS would appear to be the means for self-evaluation of acute pain intensity in an emergency department.