Moderate Baseline Pain Research Articles

Can Baseline Characteristics Predict Successful Outcomes after Individual, Physiotherapist-Led Rehabilitation in Patients with Chronic Musculoskeletal Pain?

No strong and consistent variables to predict outcome after pain rehabilitation have been reported in patients with chronic musculoskeletal pain. The aim of the present study was to clarify if baseline variables could predict successful outcome after a unique, individualized, physiotherapist-led rehabilitation of nine sessions. In 274 individuals with severe chronic musculoskeletal pain, the risk ratio (RR) and 95% confidence intervals (CIs) were estimated for potentially predictive baseline variables on successful outcomes of pain management, overall health, and pain rating. Statistically significant results show that patients rating moderate or severe baseline pain were in both cases 14% less likely to improve pain management compared to patients rating mild baseline pain (RR = 0.86; 95% CI 0.77-0.97, RR = 0.86; 95% CI 0.74-1.00). Patients with the shortest pain duration were 1.61 times more likely to improve overall health (RR = 1.61; 95% CI 1.13-2.29) compared to patients reporting the longest pain duration (>5 years). Patients reporting anxiety/depression or severe pain were in both cases 1.48 times more likely to improve overall health compared to better baseline presentations (RR = 1.48; 95% CI 1.16-1.88, RR = 1.48; 95% CI 1.03-2.15). Patients with regional/generalized pain were 36% less likely to rate pain reduction (RR = 0.64; 95% CI 0.41-1.00) compared to patients rating localized baseline pain. Of 17 potentially predictive baseline variables, four reached statistical significance for at least one of the three outcomes; although none of them for all three outcomes. Of 17 potentially predictive baseline variables, mild pain ratings, short pain duration, and localized baseline pain were statistically significantly associated with improvements after individual, physiotherapist-led rehabilitation for patients with chronic musculoskeletal pain. This suggests that this type of rehabilitation probably should be offered early in the pain process. Reporting anxiety/depression or severe pain at the baseline did not hinder the improvements of overall health.

Nociception level index variations in patients with complex regional pain syndrome: a pilot study.

The nociception level index (NOL) is a multi-parameter index that incorporates changes in autonomic parameters to evaluate nociception, with more painful stimuli causing more pronounced index variations. How this nociception monitor relates to the pain experience is uncertain, and patients with chronic pain may respond differently to acute pain due to alterations in pain processing. The goal of this pilot study was to evaluate NOL index variations after a painful physiotherapy exercise in patients with upper limb complex regional pain syndrome. Baseline NOL indexes were recorded using a finger probe (PMD-200™Monitor, Medasense, Israel) and patient reported baseline pain scores using an 11-point numeric rating scale (NRS). Patients then performed a painful physiotherapy exercise and NOL index and pain scores were again recorded. The same procedure and recordings were repeated after a stellate ganglion block. Data were analyzed using a paired Student T test and a P value < 0.05 was considered statistically significant. Twenty patients (12/20 female, 10/20 right-sided) were included in this study. Patients reported moderate baseline pain (4.0 ± 2.7) despite having a low baseline NOL index (7.66 ± 5.76 out of 100). NRS and NOL index scores increased significantly during exercise, both before and after the block. The NOL index increased significantly when patients reported increased pain, indicating that it could eventually be useful in the objective assessment of acute pain in the chronic pain patients. However, NOL index was not able to reflect pain levels at rest, before the painful stimulation, in this chronic pain population. Further studies are needed to better assess NOL index utility at rest and to confirm these findings in this specific chronic pain population.

Drug Therapeutic in the Subacute and Chronic Phase of Chikungunya Virus Infection

Background: Chikungunya fever is an infectious disease that can evolve to a subacute or chronic condition, with changes in the daily activities of patients. Drugs that aim to reduce these symptoms are used, such as corticoids (acute phase) and disease-modifying anti-rheumatic drugs (chronic phase). Objective: To evaluate the clinical response to drug therapy in the subacute and chronic phase of infection by the Chikungunya virus. Methodology: A prospective and a retrospective study with patients with subacute and chronic Chikungunya infection, out at the infection and autoimmunity outpatient clinic at the Nucleus of Tropical Medicine, from January 2016 to December 2019, in the morning of Thursdays. The patient was observed in the Baseline, first and second return, and drugs were introduced according to the stage of the disease with subsequent reassessment. The Visual Analogue Scale (VAS) was applied to all evaluation moments. Results: 101 patients were evaluated, and arthralgia was the predominant symptom in the three evaluated moments. According to the VAS, moderate baseline pain was observed in 58.1% and 58.6% of subacute and chronic cases, respectively. On the first return, moderate pain still predominated in 46.2% in subacute cases and 43% in chronic cases. In the second visit, all patients were in the chronic phase of the disease, 43.8% had VAS with no pain. Regarding the number of compromised joints in the Baseline, polyarticular involvement predominated in both subacute (79%) and chronic (74.1%) cases, in the first return, oligoarticular involvement predominated in 53.8% of subacute cases and 54.7% in chronic cases and, the second return, 40.6% of the patients had oligoarticular involvement and 43.8% had no joint involvement. As for the use of medications in the Baseline, 33.4% of subacute cases used antiinflammatory drugs, and 40% of chronic cases used corticosteroids. At the first visit, 25% of chronic patients were already using combined corticosteroids and methotrexate and 15% were using only methotrexate. In the second return, 35.1% used combined methotrexate and corticosteroids, and 64.9% used only methotrexate. Safety in the use of methotrexate was observed in the context of CHIKV treatment, as the number of adverse reactions was minimal (three patients) and the medication was well tolerated. Conclusion: It was observed that with the adjustment of the medications, there was a reduction in joint impairment, VAS showed mild pain indexes and in some cases with no pain, showing the benefit of using therapy in subacute and chronic cases and improving quality of life of these users.

Virtual Reality Analgesia for Children With Large Severe Burn Wounds During Burn Wound Debridement.

The objective of this study was to compare the effect of adjunctive virtual reality vs. standard analgesic pain medications during burn wound cleaning/debridement. Participants were predominantly Hispanic children aged 6–17 years of age, with large severe burn injuries (TBSA = 44%) reporting moderate or higher baseline pain during burn wound care. Using a randomized between-groups design, participants were randomly assigned to one of two groups, (a) the Control Group = pain medications only or (b) the VR Group = pain medications + virtual reality. A total of 50 children (88% Hispanic) with large severe burns (mean TBSA > 10%) received severe burn wound cleaning sessions. For the primary outcome measure of worst pain (intensity) on Study Day 1, using a between groups ANOVA, burn injured children in the group that received virtual reality during wound care showed significantly less pain intensity than the No VR control group, [mean worst pain ratings for the No VR group = 7.46 (SD = 2.93) vs. 5.54 (SD = 3.56), F(1,48) = 4.29, <0.05, MSE = 46.00]. Similarly, one of the secondary pain measures, “lowest pain during wound care” was significantly lower in the VR group, No VR = 4.29 (SD = 3.75) vs. 1.68 (2.04) for the VR group, F(147) = 9.29, < 0.005, MSE = 83.52 for Study Day 1. The other secondary pain measures showed the predicted pattern on Study Day 1, but were non-significant. Regarding whether VR reduced pain beyond Study Day 1, absolute change in pain intensity (analgesia = baseline pain minus the mean of the worst pain scores on Study days 1–10) was significantly greater for the VR group, F(148) = 4.88, p < 0.05, MSE = 34.26, partial eta squared = 0.09, but contrary to predictions, absolute change scores were non-significant for all secondary measures.

Reverse total shoulder arthroplasty for patients with minimal preoperative pain: a matched-cohort analysis

Profound improvements in function have been described in patients following reverse total shoulder arthroplasty (RSA). Previous studies have demonstrated young age, high preoperative function, and neurologic dysfunction to be predictors of poor functional improvement. However, no study to date has focused on patients electing to undergo RSA for function more than pain. The purpose of this study was to compare the outcomes of RSA in patients with minimal preoperative pain with those in patients who have higher baseline pain. We performed a retrospective matched-cohort study of RSA patients treated by a single surgeon with a minimum of 2 years' follow-up. Patients with at least moderate baseline pain (function-pain group), predefined by existing literature as a visual analog scale pain score > 3, were matched 3:1 based on sex, indication, and age to patients with minimal pain (function group), defined as a visual analog scale score ≤ 3. Patient-reported outcome measures, active range of motion, and overall satisfaction were compared. The percentage of maximal improvement in outcomes and the proportion of patients exceeding the established threshold that predicts excellent satisfaction were also compared. A total of 260 patients (195 in function-pain group and 65 in function group) were selected for matched analysis with a similar sex distribution; the mean age was 73.1 years, and the mean follow-up period was 50 months. No differences in most recent postoperative function, overall improvement in functional scores, and active motion were found between patients in the 2 groups (P > .05). However, pain scores improved only in patients with at least moderate baseline pain (P < .0001). Patient satisfaction was significantly different (P = .035), as 10.8% of patients who elected to undergo RSA for function were unsatisfied. The function cohort also had worse percentage of maximal Simple Shoulder Test score (P = .034) and American Shoulder and Elbow Surgeons score (P < .0001) improvement, and a lower proportion of these patients exceeded the threshold for the percentage of maximal improvement that predicts an "excellent" outcome (P < .0001). RSA patients with minimal preoperative pain achieve significant improvements in function and motion similar to those who choose to undergo RSA for both pain and function, but they are less satisfied and are less likely to achieve an excellentoutcome. Patients electing to proceed with RSA with minimal pain should be counseled accordingly.

The efficacy of pregabalin for the treatment of neuropathic pain in Japanese subjects with moderate or severe baseline pain.

PurposeAlthough analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP.Patients and methodsData were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13–16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day.ResultsMean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema.ConclusionPregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity.ClinicalTrials.gov identifiersNCT0039490130, NCT0055347522, NCT0040774524

Self-efficacy and risk of persistent shoulder pain: results of a Classification and Regression Tree (CART) analysis

ObjectivesTo (i) identify predictors of outcome for the physiotherapy management of shoulder pain and (ii) enable clinicians to subgroup people into risk groups for persistent shoulder pain and disability.Methods1030 people...

Exploratory Study of 6-Month Pain Trajectories in Individuals With Predominant Patellofemoral Osteoarthritis: A Cohort Study.

Knowledge of patellofemoral osteoarthritis (OA) pain trajectories is vital to helping clinicians and patients make shared disease-specific decisions regarding treatment options and coping strategies. To describe the pain trajectories of people living with patellofemoral OA who present to a chronic care management program, and to explore baseline characteristics associated with different trajectories. In this prospective longitudinal cohort study, 88 participants who presented to a chronic care management program reported their worst pain over the previous week at baseline and at 6, 12, 18, and 26 weeks using a 10-cm visual analog scale. Trajectories (classes) were identified using latent class growth analysis. Demographics, pain, physical performance, strength, quality of life, mental health, and lower limb/foot structural measures obtained at baseline were assessed for association with trajectory class membership. Individuals in class 1 (28%) exhibited high, persistent pain from baseline (7.8 ± 1.7 cm), which continued over time (P = .52). Class 2 (57%) displayed moderate baseline pain (4.8 ± 1.8 cm), which also remained persistent (P = .97). Individuals in class 3 (15%) showed low, improving pain (baseline pain, 2.6 ± 1.2 cm) over time (P = .017). At baseline, poor Knee injury and Osteoarthritis Outcome Score (KOOS) scores, local and proximal sensitivity to pressure, and lower knee extensor strength were associated with increased odds of following the high-pain trajectory (range [95% confidence interval], 1.03 [1.00, 1.07] to 16.24 [2.53, 104.34]). Distinct pain trajectories appear to exist in people with patellofemoral OA presenting to a chronic care management program. Baseline variables may be useful for identifying individuals at risk of poorer prognosis. Larger studies are needed to confirm the efficacy of this finding. Prognosis, level 2b. J Orthop Sports Phys Ther 2019;49(1):5-16. Epub 12 Sep 2018. doi:10.2519/jospt.2019.8354.

Comparison of the efficacy and safety of pregabalin for postherpetic neuralgia in Chinese and international patients.

PurposePregabalin is indicated for postherpetic neuralgia (PHN) in multiple countries, including China. This analysis compared pregabalin efficacy and safety in Chinese and international patients with PHN.Patients and methodsData from Chinese and international randomized, double-blind, placebo-controlled trials were compared. Pregabalin was administered at fixed (150, 300, or 600 mg/day) or flexible (150–600 mg/day) doses. The main efficacy measure was mean pain score change at endpoint on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. Secondary efficacy measures included proportions of 30% and 50% pain responders, pain-related sleep interference (PRSI) scores, and proportions of Patient Global Impression of Change (PGIC) responders. The incidences of serious adverse events (SAEs) and adverse events (AEs) were used to assess safety. The effect of baseline pain severity on efficacy was tested. The proportions of patients with severe baseline pain who had moderate or mild pain at endpoint were also assessed.ResultsA total of 1166 patients were analyzed: 312 Chinese and 854 international. Overall, results were similar between Chinese and international patients. Pregabalin statistically significantly improved mean pain score versus placebo (least squares mean difference [95% CIs]: Chinese, −0.8 [–1.2, −0.5]; international, −1.3 [–1.6, −1.0]; both p<0.001). Pregabalin was statistically significantly better than placebo in Chinese and international patient groups in the proportions of 30% and 50% pain responders, PRSI scores, and proportions of PGIC responders. Baseline pain severity did not affect efficacy, except for some measures in Chinese patients with moderate baseline pain. Similar proportions of pregabalin-treated patients with severe baseline pain had moderate or mild pain at endpoint in both groups. SAE and AE profiles were comparable in Chinese and international patient groups, except incidences were commonly higher in international patients.ConclusionChinese and international patients with PHN exhibit comparable pregabalin efficacy and safety, highlighting the utility of pregabalin for diverse PHN patient populations.

Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials.

PurposeUse of nonopioid analgesics (including nonsteroidal anti-inflammatory drugs) for postoperative pain management can reduce opioid consumption and potentially prevent opioid-related adverse events. This study examined the postoperative opioid-sparing effect of repeated-dose injectable diclofenac formulated with hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac.Patients and methodsPooled data from two double-blind, randomized, placebo- and active comparator-controlled Phase III trials were analyzed. Patients received HPβCD-diclofenac, placebo, or ketorolac by intravenous injection every 6 hours for up to 5 days following abdominal/pelvic or orthopedic surgery. Rescue opioid use was evaluated from the time of first study drug administration to up to 120 hours following the first dose in the overall study population and in subgroups defined by baseline pain severity, age, and HPβCD-diclofenac dose.ResultsOverall, 608 patients received ≥1 dose of study medication and were included in the analysis. While 93.2% of patients receiving placebo required opioids, the proportion of patients requiring opioids was significantly lower for patients receiving HPβCD-diclofenac (18.75, 37.5, or 50 mg) or ketorolac (P<0.005 for all comparisons). Mean cumulative opioid dose and number of doses were significantly lower among patients receiving HPβCD-diclofenac versus placebo for the 0–24 through 0–120 hour time periods (P<0.0001), as well as versus ketorolac for the 0–72 through 0–120 hour time periods (P<0.05). HPβCD-diclofenac significantly reduced opioid consumption versus placebo in subgroups based on baseline pain severity (moderate, severe) and age (<65 years, ≥65 years) from the 0–24 hour period onward. When compared to ketorolac, HPβCD-diclofenac also significantly reduced cumulative opioid consumption among patients with moderate baseline pain (0–72 through 0–120 hours) and opioid dose number among patients ≥65 years old (0–24 through 0–120 hours).ConclusionHPβCD-diclofenac can reduce postoperative opioid requirements. As this analysis was not powered to compare opioid-related adverse event rates, follow-up studies examining the clinical impact of HPβCD-diclofenac’s opioid sparing are warranted.

Performance of the Angle Labor Pain Questionnaire During Initiation of Epidural Analgesia in Early Active Labor.

The Angle Labor Pain Questionnaire (A-LPQ) is a new, 22-item multidimensional psychometric questionnaire that measures the 5 most important dimensions of women's childbirth pain experiences using 5 subscales: The Enormity of the Pain, Fear/Anxiety, Uterine Contraction Pain, Birthing Pain, and Back Pain/Long Haul. Previous work showed that the A-LPQ has overall good psychometric properties and performance during early active labor in women without pain relief. The current study assessed the tool's sensitivity to change during initiation of labor epidural analgesia with the standardized response mean (SRM, primary outcome). Two versions of the A-LPQ were administered once, in each of 2 test sessions, by the same trained interviewer during early active labor. The sequence of administration was randomized (ie, standard question order version [Test 1] followed by mixed version [Test 2] or vice versa). Test 1 was completed before epidural insertion; Test 2 commenced 20 to 30 minutes after the test dose. Providers assessed/treated pain independently of the study. Sensitivity to change was assessed using SRMs, Cohen's d, and paired t tests. Overall pain intensity was concurrently examined using Numeric Rating Scale and the Verbal Rating Scale (VRS); coping was assessed with the Pain Mastery Scale. Changes in pain were measured with the Patient Global Impression of Change Scale. Internal consistency was assessed with Cronbach's α. Concurrent validity with other tools was assessed using Spearman's rank correlation coefficient. A total of 51 complete datasets were analyzed. Most women reported moderate (63%, 32/51) or severe (18%, 9/51) baseline pain on VRS scores during Test 1; 29% (15/51) reported mild pain, and 6% (3/51) reported moderate pain during Test 2. Approximately 90% (46/51) of women reported much or very much improved pain at the end of testing. Cronbach's α for A-LPQ summary scores was excellent (0.94) and ranged from 0.78 (acceptable) to 0.92 (excellent) for subscales (Test 1). Large SRMs were found for A-LPQ summary scores (1.6, 95% CI: 1.2, 2.1) and all subscales except the Birthing Pain subscale (moderate, 0.60, 95% CI: 0.23, 0.97). Significant (P < .001) differences were found between A-LPQ summary scores and between all subscales on paired t tests. Correlations between A-LPQ summary and Numeric Rating Scale scores (overall pain intensity) were strong (ρ > 0.73), correlations were moderate (ρ > 0.5) with VRS scores and coping scores (ρ > 0.67). Findings support A-LPQ use for measurement of women's childbirth pain experiences during initiation of labor epidural analgesia during early active labor. Combined with our previous work, they also support the use of the A-LPQ in late labor and at delivery.

Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults

ABSTRACTPrevious studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm2 Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0–100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

The efficacy of pregabalin in patients with moderate and severe pain due to diabetic peripheral neuropathy

Objective To compare the therapeutic response to pregabalin in patients with moderate or severe painful diabetic peripheral neuropathy (pDPN).Research design and methods Data were pooled from 11 placebo-controlled trials to evaluate the efficacy of pregabalin flexible or fixed dose (150, 300 or 600 mg/day) in pDPN patients with mean baseline pain scores of ≥4 to <7 (moderate) or ≥7 to ≤10 (severe). Last observation carried forward imputation was used.Study number/ClinicalTrials.gov identifier 1008-014/-, 1008-029/-, 1008-040/-, 1008-131/-, 1008-149/-, 1008-000-155/-, A0081030/NCT00156078, A0081060/NCT00159679, A0081071/NCT00143156, A0081081/NCT00301223, A0081163/NCT00553475.Main outcome measures Pregabalin-mediated change in pain, pain-related sleep interference (PRSI) and patient global impression of change (PGIC) were compared versus placebo and between moderate and severe pain cohorts. Adverse events (AEs) were reported.Results At baseline, 1816 patients had moderate pain (pregabalin, n = 1189) and 1119 patients had severe pain (pregabalin, n = 720). Pregabalin significantly reduced pain scores at endpoint compared with placebo when patients of all pain levels were combined (all doses; p < 0.05). In the moderate and severe pain cohorts, pregabalin treatment (300, 600 mg/day or flexible) significantly reduced mean pain scores at endpoint compared with placebo (p < 0.01). Pain reduction was greatest in patients with severe baseline pain compared with moderate baseline pain (pregabalin 300, 600 mg/day or flexible; p < 0.0001). Pregabalin improved PRSI and PGIC in the moderate and severe cohorts compared with placebo. The greatest improvement in PRSI also occurred in the severe cohort. Treatment-emergent AEs, most commonly dizziness, somnolence and peripheral edema, occurred more frequently in patients treated with pregabalin compared with placebo.Conclusions Pregabalin was effective in pDPN patients with both moderate and severe baseline pain. Patients with severe pain exhibited greater improvements in pain and PRSI than patients with moderate pain. Pain severity may, in part, predict therapeutic response to pregabalin.

The safety and efficacy of pregabalin for treating subjects with fibromyalgia and moderate or severe baseline widespread pain

Objective To evaluate pregabalin’s efficacy (≤12 weeks) for pain relief and sleep improvement in patients with fibromyalgia (FM) and moderate-to-severe baseline pain.Research design and methods Data were pooled from five randomized, double-blind, placebo-controlled, phase III clinical trials of pregabalin (300–450 mg/day) for FM treatment. Subjects, aged ≥18 years, had moderate (≥4–<7) or severe (≥7–10) mean baseline pain scores. Analyses included mixed effects repeated measures (MMRM), baseline observation carried forward (for parameters without enough data points for MMRM), or logistic regression.Clinical trial registration Study number/ClinicalTrials.gov number: A0081056/NCT00645398, A0081077/NCT00230776, A0081100/NCT00333866, A0081208/NCT00830167.Main outcomes measures Endpoints included mean change in pain and sleep quality scores (Weeks 8 and 12), patient-reported outcomes, and adverse events (AEs).Results Baseline demographic characteristics were comparable between pregabalin and placebo in both baseline pain severity groups. Mean ± SD baseline pain severity scores were equivalent between pregabalin and placebo within moderate (5.8 ± 0.8) or severe pain (7.9 ± 0.7) subgroups. All subjects reported reduced pain and improved sleep quality through Weeks 8 and 12, with larger effects observed with pregabalin over placebo and with baseline severe over moderate pain (all p < 0.01). Pregabalin was generally well tolerated, AE findings were consistent with previously published trials, and AE profiles were similar between moderate and severe baseline pain subgroups. Limitations of this pooled analysis included differences in individual trial designs (e.g., dosing schedules, racial distribution, exclusion criteria that did not enroll mild severity patients).Conclusions Pregabalin was efficacious through 12 weeks for reducing pain and improving sleep quality in FM patients with baseline moderate or severe pain, with larger effects in the baseline severe pain subgroup. AEs were consistent with pregabalin’s known safety profile and did not differ between moderate and severe pain subgroups.

A randomized, placebo-controlled trial of the analgesic efficacy and safety of the p38 MAP kinase inhibitor, losmapimod, in patients with neuropathic pain from lumbosacral radiculopathy.

Preclinical studies have demonstrated involvement of p38 mitogen-activated protein kinase signaling pathways in the development of persistent pain after peripheral nerve injury. A double-blind, randomized, placebo-controlled study was undertaken to evaluate the analgesic efficacy of losmapimod (GW856553), a novel p38α/β inhibitor, in patients with chronic neuropathic pain due to lumbosacral radiculopathy. A total of 144 patients with at least moderate baseline pain intensity (average daily score of ≥4 on an 11-point pain intensity numeric rating scale) were randomized to receive losmapimod, 7.5 mg bid orally or placebo. All patients underwent a blinded placebo run-in period for 7 days before receiving losmapimod/placebo for 28 days. Efficacy and safety evaluations were undertaken weekly. The adjusted mean treatment difference for the change from baseline to week 4 in numeric rating scale was -0.36 U (95% confidence interval, -0.84, 0.13; P=0.149) in favor of losmapimod over placebo; this was not considered clinically meaningful. Statistically significant differences in favor of losmapimod were observed, however, for several secondary endpoints of emotional, physical, and social functioning: Oswestry Disability Index; Profile of Mood States total score; Short-Form 36 Health Survey physical functioning, bodily pain, general health, role emotional, social functioning, and vitality domains; and Short-Form 36 physical, and mental components. There were no unexpected findings related to safety or tolerability following treatment with losmapimod. Losmapimod could not be differentiated from placebo in terms of analgesia. The lack of response could reflect insufficient losmapimod levels in the spinal cord or differences between lumbosacral radiculopathy and animal models of neuropathic pain.

Reduction of Bodily Pain in Response to an Online Positive Activities Intervention

Inducing temporary positive states reduces pain and increases pain tolerance in laboratory studies. We tested whether completing positive activities in one's daily life produces long-term reductions in self-reported bodily pain in a randomized controlled trial of an online positive activities intervention. Participants recruited via the Web were randomly assigned to complete 0, 2, 4, or 6 positive activities administered online over a 6-week period. Follow-up assessments were collected at the end of 6 weeks and at 1, 3, and 6 months postintervention. We used linear mixed effects models to examine whether the intervention reduced pain over time among those who had a score <67 on the bodily pain subscale of the Short Form-36 at baseline (N = 417; pain scores range from 0 to 100; higher scores indicate less pain). Mean pain scores improved from baseline to 6 months in the 2-activity (55.7 to 67.4), 4-activity (54.2 to 71.0), and 6-activity (50.9 to 67.9) groups. Improvements were significantly greater (P < .05) in the 4-activity and 6-activity groups than in the 0-activity control group (54.1 to 62.2) in unadjusted and adjusted models. This study suggests that positive activities administered online can reduce bodily pain in adults with at least mild to moderate baseline pain. PerspectiveThis study demonstrates that teaching people simple positive activities can decrease reported levels of bodily pain; moreover, these activities can be administered over the internet, a potential avenue for broadly disseminating health interventions at relatively low costs and with high sustainability.

Effects of Cabozantinib on Pain and Narcotic Use in Patients with Castration-resistant Prostate Cancer: Results from a Phase 2 Nonrandomized Expansion Cohort

BackgroundPain negatively affects quality of life for cancer patients. Preliminary data in metastatic castration-resistant prostate cancer (mCRPC) suggested a benefit of the oral tyrosine kinase inhibitor cabozantinib to pain palliation. ObjectiveProspective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC. Design, setting, and participantsThis was a nonrandomized expansion (NRE) cohort (n=144) of a phase 2 randomized discontinuation trial in docetaxel-refractory mCRPC patients. Pain and interference of symptoms with sleep and general activity were electronically self-reported daily for 7-d intervals at baseline and regularly scheduled throughout the study. Mean per-patient scores were calculated for each interval. Narcotic use was recorded daily during the same intervals. InterventionOpen-label cabozantinib (100mg or 40mg). Outcome measurements and statistical analysisThe following stringent response definition was used: clinically meaningful pain reduction (≥30% improvement in mean scores from baseline) confirmed at a later interval without concomitant increases in narcotics. Only patients with moderate or severe baseline pain were analyzed. Results and limitationsSixty-five patients with moderate or severe baseline pain were evaluable. Of these, 27 (42%) experienced pain palliation according to the stringent response definition. Thirty-seven patients (57%) had clinically meaningful pain relief at two consecutive intervals, reported ≥6 wk apart in the majority. Forty-four patients (68%) had palliation at one or more intervals; 36 (55%) decreased narcotics use during one or more intervals. Clinically meaningful pain reduction was associated with significant (p ≤ 0.001) improvements in sleep quality and general activity. A limitation of this study was its open-label design. ConclusionsCabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients’ narcotic use, and improved patient functioning, thus meriting prospective validation in phase 3 studies. Patient summaryWe evaluated the potential of cabozantinib to improve symptoms in patients with metastatic prostate cancer that no longer responds to standard therapies. We saw a promising reduction in pain and reduced need for narcotic painkillers. Larger, well-controlled trials are necessary to confirm these findings.

How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative.

IntroductionThe aim of this analysis was to describe comprehensively the cross-sectional and longitudinal patterns of analgesic and nutraceutical medication use for knee osteoarthritis (OA) in a contemporary US cohort and to investigate associated demographic and clinical factors.MethodsBaseline, 12, 24 and 36 month data were obtained retrospectively from the National Institutes of Health Osteoarthritis Initiative. Participants had symptomatic radiographic knee OA. Multiple binary logistic regression models identified characteristics independently associated with the use of analgesics or nutraceuticals.ResultsWe included 987 subjects (55.9% female, mean age 61.5 years, 71.0% white). At baseline, 68.2% reported frequent use of a conventional analgesic or nutraceutical for joint pain (for more than half of the previous month). Non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently reported medications (26.8%), even in those more than 75-years old. Multiple conventional analgesics were used by 11.9%. Frequent analgesic use was more likely in women (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.3 to 2.3)) and people with more pain (moderate 1.7 (1.2 to 2.4); severe 3.1 (2.1 to 4.7)); nutraceutical use was less likely in non-whites (0.4 (0.3 to 0.6)), those more than 74-years old (0.6 (0.3 to 0.9)) and those with comorbidities (0.6 (0.5 to 0.9)) and more likely in people with Kellgren-Lawrence (KL) grade 4 (2.2 (1.5 to 3.3)). Overall there was no change in the proportion of participants frequently using prescription or over the counter (OTC) analgesics at 36 months, although most people had changed medication type; of those using a traditional analgesic at baseline approximately one third were still using the same type at 36 months (ranging from 26.2% of baseline prescription NSAID users to 40.6% of baseline acetaminophen users). All participants reporting baseline analgesic use also reported 36 month analgesic use. Female participants (OR 95% CI 1.2 to 3.2, P = 0.009), those with high body mass index (1.2 to 4.8, P = 0.010) and those with moderate (1.6 to 2.6, P = 0.090) or severe (1.8 to 12.0, P = 0.002) baseline pain were more likely to use pain medication during the 36 month follow-up period; participants more than 75-years old were less likely (0.2 to 1.0, P = 0.053).ConclusionsMost people with knee OA used pharmacological therapies frequently, and use appeared to be according to American College of Rheumatology recommendations. Change in medication type used was common. Persistent non-prescription NSAID use in older people is an area of concern.

Influence of Patient Coaching on Analgesic Treatment Adjustment: Secondary Analysis of a Randomized Controlled Trial

ContextFor patients with cancer-related pain and their physicians, routine oncology visits are an opportunity to adjust the analgesic regimen and secure better pain control. However, treatment intensification occurs haphazardly in practice. ObjectivesTo estimate the effect of patient-centered tailored education and coaching (TEC) on the likelihood of analgesic treatment adjustment during oncology visits, and in turn, the influence of treatment adjustment on subsequent cancer pain control, we studied patients enrolled in a randomized trial of TEC. MethodsJust before a scheduled oncology visit, 258 patients with at least moderate baseline pain received TEC or control; just after the same visit, they reported on whether the physician recommended a new pain medicine or a change in dose of an existing medicine. Pain severity and pain-related impairment were measured two, six, and 12 weeks later. ResultsPatients assigned to TEC were more likely than controls to report a change in the analgesic treatment regimen (60% vs. 36%, P<0.01); significant effects persisted after adjustment for baseline pain, study site, and physician (adjusted odds ratio 2.61, 95% confidence interval 1.55, 4.40, P<0.01). In a mixed-effects repeated measures regression, analgesic change (but not TEC itself) was associated with a sustained decrease in pain severity (P<0.05). ConclusionTEC increases the likelihood of self-reported, physician-directed adjustments in analgesic prescribing, and treatment intensification is associated with better cancer pain outcomes.

Satisfaction With and Confidence in Needle-Free Subcutaneous Sumatriptan in Patients Currently Treated with Triptans

To evaluate patient satisfaction with and confidence in Sumavel® DosePro® (needle-free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks. Sumavel DosePro is a needle-free, single-use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing. In this open-label, multicenter study, Sumavel DosePro was self-administered for ≤4 migraine attacks (over a ≤60-day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (i.e., baseline satisfaction ranging from satisfied to very dissatisfied). Treatment satisfaction was measured via the Patient Perception of Migraine Questionnaire, revised (PPMQ-R). Among the 212 patients using Sumavel DosePro to treat ≥1 migraine attack, PPMQ-R Overall Satisfaction (primary endpoint) increased significantly from baseline to the end of treatment (mean ± SD 65.7 ± 19.8 vs. 73.7 ± 29.1, P = .0007), an improvement that met the criterion for clinical significance. From baseline to the end of treatment, PPMQ-R scores also improved significantly for Efficacy (62.2 ± 17.6 vs. 76.2 ± 23.7, P < .0001), Functionality (59.0 ± 22.3 vs. 73.8 ± 25.3, P < .0001), and Tolerability (83.9 ± 13.1 vs. 86.4 ± 15.0, P = .02), but declined for Ease of Use (82.6 ± 15.3 vs 67.8 ± 27.6, P < .0001). For all global satisfaction domains, the percentage of patients satisfied or very satisfied increased from baseline to the end of treatment (Overall Satisfaction 36.3% vs. 64.0%, Satisfaction with Medication Effectiveness 40.1% vs. 68.2%, Satisfaction with Side Effects 48.6% vs. 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval [CI] 35.4, 46.9 vs. end of treatment: 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain-free response, sustained 24-hour pain relief and pain-free response) were consistent with those previously observed with needle-based sumatriptan. Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks.