Reduction In Pain Intensity Scores Research Articles

Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundBreakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients.MethodsThe trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30).ResultsA total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs.ConclusionTreatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial.Trial registrationClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.

Musculoskeletal Pain in Parkinson's Disease.

BackgroundMusculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain.ObjectivesTo investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD.MethodsWe enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain.ResultsTwo hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07–2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63–6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life.ConclusionsThe lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Derivation of a Risk Assessment Tool for Prediction of Long-Term Pain Intensity Reduction After Physical Therapy.

RationaleRisk assessment tools can improve clinical decision-making for individuals with musculoskeletal pain, but do not currently exist for predicting reduction of pain intensity as an outcome from physical therapy.Aims and ObjectiveThe objective of this study was to develop a tool that predicts failure to achieve a 50% pain intensity reduction by 1) determining the appropriate statistical model to inform the tool and 2) select the model that considers the tradeoff between clinical feasibility and statistical accuracy.MethodsThis was a retrospective, secondary data analysis of the Optimal Screening for Prediction of Referral and Outcome (OSPRO) cohort. Two hundred and seventy-nine individuals seeking physical therapy for neck, shoulder, back, or knee pain who completed 12-month follow-up were included. Two modeling approaches were taken: a longitudinal model included demographics, presence of previous episodes of pain, and regions of pain in addition to baseline and change in OSPRO Yellow Flag scores to 12 months; two comparison models included the same predictors but assessed only baseline and early change (4 weeks) scores. The primary outcome was failure to achieve a 50% reduction in pain intensity score at 12 months. We compared the area under the curve (AUC) to assess the performance of each candidate model and to determine which to inform the Personalized Pain Prediction (P3) risk assessment tool.ResultsThe baseline only and early change models demonstrated lower accuracy (AUC=0.68 and 0.71, respectively) than the longitudinal model (0.79) but were within an acceptable predictive range. Therefore, both baseline and early change models were used to inform the P3 risk assessment tool.ConclusionThe P3 tool provides physical therapists with a data-driven approach to identify patients who may be at risk for not achieving improvements in pain intensity following physical therapy.

Effect of Early Management on Pain and Depression in Patients with Pancreatobiliary Cancer: A Randomized Clinical Trial.

Background: The present study assessed whether early palliative care (EPC) targeting pain and depression and automated symptom monitoring could improve symptoms in patients with advanced pancreatobiliary cancer. Methods: Patients diagnosed with pathologically confirmed locally advanced or metastatic pancreatic or biliary tract cancer who had cancer-related pain (brief pain inventory (BPI) worst pain score >3) and/or depression (Center for Epidemiological Studies—Depression Scale (CES-D) >16) were randomized within 8 weeks after diagnosis to receive EPC or on-demand palliative care (n = 144 each). EPC included (1) nursing assessment of pain and depression, (2) pain control based on National Comprehensive Cancer Network guidelines, (3) depression control by psychoeducation and/or consultation with a psychiatric specialist, and (4) patient education. The primary end points were ≥50% reductions from baseline to week 4 in pain and depression scores. Results: The proportion of patients in the EPC and usual care groups with ≥50% reductions in pain (29.5% vs. 25.2%; p = 0.4194) and depression (30.8% vs. 36.8%; p = 0.5732) scores from baseline to week 4 did not differ significantly. The proportion of patients with BPI worst pain score ≤3 was significantly higher (51.1% vs. 38.9%, p = 0.0404) and the reduction in pain intensity score significantly greater (1.5 vs. 1.0 points, p = 0.0318) in the EPC than in the usual care group. At 4 weeks, patients in the EPC group reported significant increases in global health status, role of functioning, nausea and vomiting, and pain scores on the European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) general questionnaire. Conclusions: Although the primary outcome was not met, this trial indicates that EPC may improve early pain relief in patients with advanced pancreatobiliary cancers.

Prevalence and Characteristics of Moderate to Severe Pain among Hospitalized Older Adults.

To investigate the prevalence, characteristics, and management of pain in older hospitalized medical patients. Medical record aggregate review. Tertiary care hospital. Individuals aged 65 and older admitted to the medicine service between November 28, 2014, and May 28, 2015. Demographic characteristics, comorbidity burden, pain characteristics, and analgesics during index hospitalization were assessed in individuals with moderate to severe pain (≥4 on 0-10 Numeric Pain Rating Scale). Of 1,267 patients admitted to the medicine service, 248 (20%) had moderate to severe pain on admission (mean age 75 ± 8, 57% female, 50% white). During hospitalization, most participants received opioids (80%) and acetaminophen (74%), and few received nonsteroidal antiinflammatory drugs (9%). Participants with chronic pain had less reduction in pain intensity score from admission to discharge than those without a history of chronic pain (mean change score 3.7 vs 4.9, p=.002) and were more likely to receive opioids, adjuvant analgesics, and other analgesics (all p<.05). Twenty percent of older adults admitted to a general medicine service had moderate to severe pain. Further research about optimal pain management in hospitalized older adults, particularly those with chronic pain, is necessary to improve care in this population.

Effects of Tactile Desensitization on Postoperative Pain After Amputation Surgery

Pain in the acute setting after amputation is complex with multiple types of pain experienced, including somatic and neuropathic. No studies have measured multiple pain control modalities while using self-management techniques for acute amputation pain. Desensitization could provide a means of pain control for somatic and neuropathic pain. The purpose of this study was to test the efficacious use and effects of tactile desensitization in managing acute postoperative pain after lower limb amputation. This was a pre-experimental repeated measure study. Pain description, intensity, anxiety, depression, and medication usage were measured during repeated time periods. Pain intensity was measured before and after each intervention along with efficacy. Of the times the intervention was self-administered (n=50) there was a statistically significant reduction in the pain level (P<.001) with large effect sizes for all paired comparisons. Participants found the intervention efficacious and feasible to use. The findings support a reduction in pain intensity scores using pain medication coupled with tactile desensitization.

Impact of a Pharmacy-Led Pain Management Team on Adults in an Academic Medical Center.

Background: Pain is a major health problem affecting more than 15% of adults in the United States. In a multidisciplinary pain management team, pharmacists can optimize pharmacotherapy quality by ensuring safe and appropriate medication use. Objective: Assess the impact of a pharmacy pain medication management service on pain-related outcomes in an adult inpatient population. Methods: This retrospective study evaluated patients who were admitted from November 2009 through November 2011 and received a pharmacy pain consult. Patients were excluded if they left against medical advice, their care was assumed by palliative care, or they had no complaint of pain when seen by the pharmacist. The primary outcome was the difference between each patient's average pain score from pre-consult to post-consult. Secondary outcomes were difference between each patient's average pain score from pre-consult to pre-discharge, overall functional improvement, pharmacist interventions, and 14-day and 30-day readmissions. Results: One hundred patients were included in the final analysis. Eight hundred twenty-one interventions were made by the clinical pharmacists. Patients displayed a significant reduction in their pre- and post-consult pain intensity scores on a 0 to 10 numerical rating scale (6.15 vs 3.25; p < .001). Likewise, a significant reduction in pain intensity scores was seen from pre-consult to pre-discharge (6.15 vs 3.6; p < .001). Overall functional improvement, specifically sleep, mobility, and appetite, was seen in 86.6% of patients. Conclusions: Pain management is an area that provides opportunities for pharmacotherapy interventions. Pharmacists' involvement in pain management on an inpatient consult service had a positive impact on pain scores and improvement in functionality.

Breast cancer-related lymphedema: a randomized controlled pilot and feasibility study.

Chronic lymphedema occurs frequently in breast cancer patients and is associated with significant morbidity and reduced quality-of-life. In this pilot study, the authors (1) addressed whether conducting a larger randomized controlled trial of aqua lymphatic therapy (ALT) would be feasible and (2) estimated the extent to which ALT combined with home-based exercise compared with home-based exercise alone would reduce arm disability in patients with breast cancer-related lymphedema. Twenty-five women with breast cancer-related lymphedema were randomized to either ALT in addition to a home land-based exercise program (ALT group; n = 13) or to a home land-based exercise program alone (control group; n = 12). The participants were evaluated before and after a 12-wk intervention period composed of weekly pool exercise sessions. Main outcome measures were arm volume, arm disability, pain, and quality-of-life. At follow-up, there was no statistical difference between the control and ALT groups in any of the outcomes, except for present pain intensity. At the end of the study period, there was no change in the lymphedematous limb volume in either group. Grip strength was improved in both groups. Only the ALT group showed a statistically significant difference with a reduction in pain intensity score and arm disability. Furthermore, quality-of-life significantly improved only in the ALT group. Conducting a larger randomized controlled trial would be feasible. In comparison with the beginning of the intervention, the participants in the ALT group showed significant beneficial changes after 12 wks of treatment, whereas the control group did not improve. ALT did not make the lymphedema volume worse and therefore may serve as a safe alternative to land-based treatments of breast cancer-related lymphedema.

A randomized, double-blind, placebo-controlled study of the efficacy and safety of MNK-795, a dual-layer, biphasic, immediate-release and extended-release combination analgesic for acute pain

Objective:To investigate the efficacy and safety of a bilayer combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (OC/APAP ER) in patients with moderate to severe pain using an established acute pain model.Research design and methods:This was a randomized, double-blind, placebo-controlled trial. Adult patients were included in the study if they had a pain intensity score ≥4 on a 0–10 numerical rating scale after bunionectomy surgery, and were randomized (1:1) to receive four doses (two tablets q12h) of OC/APAP ER or placebo.Clinical trial registration:ClinicalTrials.gov identifier: NCT01484652.Main outcome measures:The primary efficacy endpoint was the summed pain intensity difference over the first 48 hours (SPID48). Secondary endpoints included SPIDs and total pain relief (TOTPAR) over the dosing intervals; time to perceptible, meaningful, and confirmed pain relief; and the proportion of patients with ≥30% reduction in pain intensity scores.Results:A total of 329 patients were enrolled, of whom 266 (OC/APAP ER, n = 135; placebo, n = 131) completed the study. The mean (SE) SPID48 was 114.9 (7.6) in the OC/APAP ER group and 66.9 (7.6) in the placebo group (P < 0.0001). SPID and TOTPAR values were significantly greater with OC/APAP ER than with placebo over all time periods analyzed, and the median times to perceptible, meaningful, and confirmed pain relief were significantly shorter. More patients showed ≥30% reduction in pain intensity scores with OC/APAP ER than with placebo at all times after 0.5 hours. OC/APAP ER was generally well tolerated. A limitation of this study was the lack of an active comparator.Conclusions:OC/APAP ER was efficacious and generally well tolerated in an established model of moderate to severe acute pain, providing an onset of analgesia in approximately 30 minutes and sustained pain relief over the 12 hour dosing period.

Evaluating Therapeutic Benefit in Postsurgical Analgesia Requires Global Assessment: An Example From Liposome Bupivacaine in Hemorrhoidectomy

Background and Objective: Interpreting analgesic efficacy based solely on measures of pain intensity can be misleading. Here, we use data from an adult hemorrhoidectomy study to demonstrate the importance of evaluating pain intensity scores with other outcome measures in interpreting analgesic study results. Methodology: We looked for coordinated outcome measures including pain intensity at rest using a numeric rating scale (NRS), postsurgical consumption of rescue medication, subject-reported results from the Brief Pain Inventory, subject satisfaction with postsurgical analgesia, and adverse events. Results: The analgesic efficacy of liposome bupivacaine was reflected in a significant reduction in pain intensity scores at each timed assessment during the first 12 to 24 hours after surgery (meanNRS at 12 hours: liposome bupivacaine, 2.2; placebo, 2.9; P = 0.04), and less consumption of opioid rescue medications thereafter through 72 hours postsurgery (mean total amount of opioids consumed: liposome bupivacaine, 10 mg; placebo, 18 mg; P = 0.0006). These observations are supported by results of other outcome measures, including time to first use of opioid rescue medication, pain-related interference of subject functionality, and subject satisfaction with postsurgical analgesia. Conclusion: Liposome bupivacaine produced superior analgesia when compared with placebo at early postoperative time points, but appropriate use of rescue medication diminished this effect after 12 hours. However, based on our assessment of multiple outcome measures used in the study, it appears that the therapeutic benefit associated with the tested analgesic lasted throughout the 72-hour study period.

Sativex successfully treats neuropathic pain characterised by allodynia: A randomised, double-blind, placebo-controlled clinical trial

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores −1.48 points vs. −0.52 points on a 0–10 Numerical Rating Scale (p=0.004; 95% CI: −1.59, −0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient’s Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.

Hypnotherapy for Children With Functional Abdominal Pain or Irritable Bowel Syndrome: A Randomized Controlled Trial

Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are highly prevalent in childhood. A substantial proportion of patients continues to experience long-lasting symptoms. Gut-directed hypnotherapy (HT) has been shown to be highly effective in the treatment of adult IBS patients. We undertook a randomized controlled trial and compared clinical effectiveness of HT with standard medical therapy (SMT) in children with FAP or IBS. Fifty-three pediatric patients, age 8-18 years, with FAP (n = 31) or IBS (n = 22), were randomized to either HT or SMT. Hypnotherapy consisted of 6 sessions over a 3-month period. Patients in the SMT group received standard medical care and 6 sessions of supportive therapy. Pain intensity, pain frequency, and associated symptoms were scored in weekly standardized abdominal pain diaries at baseline, during therapy, and 6 and 12 months after therapy. Pain scores decreased significantly in both groups: from baseline to 1 year follow-up, pain intensity scores decreased in the HT group from 13.5 to 1.3 and in the SMT group from 14.1 to 8.0. Pain frequency scores decreased from 13.5 to 1.1 in the HT group and from 14.4 to 9.3 in the SMT group. Hypnotherapy was highly superior, with a significantly greater reduction in pain scores compared with SMT (P < .001). At 1 year follow-up, successful treatment was accomplished in 85% of the HT group and 25% of the SMT group (P < .001). Gut-directed HT is highly effective in the treatment of children with longstanding FAP or IBS.

Lamotrigine for treatment of pain associated with diabetic neuropathy: Results of two randomized, double-blind, placebo-controlled studies

To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy, two replicate randomized, double-blind, placebo-controlled studies were conducted. Patients ( n = 360 per study) with painful diabetic neuropathy were randomized to receive lamotrigine 200, 300, or 400 mg daily or placebo during the 19-week treatment phase, including a 7-week dose-escalation phase and a 12-week, fixed-dose maintenance phase. The mean reduction in pain-intensity score from baseline to week 19 (primary endpoint) was greater ( p ⩽ 0.05) in patients receiving lamotrigine 400 mg than placebo in Study 2 (observed scores, −2.7 versus −1.6 on a 0- to 10-point scale). This finding was not replicated in Study 1. Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study. Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints. The 200-mg dose did not separate from placebo. In a post hoc analysis of pooled data including only patients who reached their target dose, lamotrigine 400 mg conferred greater ( p ⩽ 0.05) mean reduction in pain-intensity score from baseline to week 19 than placebo (−2.5 for 300 mg and −2.7 for 400 mg versus −2.0 for placebo). Adverse events were reported in 71–82% of lamotrigine-treated patients compared with 63–70% of placebo-treated patients. The most common adverse events with lamotrigine were headache and rash. Compared with placebo, lamotrigine (300 and 400 mg daily) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated.

This Month in Anesthesiology

This Month in Anesthesiology

Intrathecal clonidine in the treatment of intractable pain: a phase I/II study.

Epidural clonidine has been proven effective in relieving intractable cancer pain, especially neuropathic. This phase I/II study was performed to investigate if intrathecal clonidine is well tolerated and effective for long-term treatment of intractable chronic pain. Thirty-one patients, previously implanted with programmable pumps and unable to obtain adequate pain relief with opioids and adjuvant oral medications, were enrolled. Clonidine monotherapy was initiated at 1 mcg/hr and escalated to a maximum of 40 mcg/hr (960 mcg/day). Efficacy measurements included Verbal Digital Pain Ratings, and side effects were determined by physical exam and patient reports. Patients achieving 50% or greater reduction in pain intensity scores in the dose-titration phase continued for long-term follow-up. Twenty-two patients (71%) entered long-term follow-up with intrathecal clonidine; nine patients (29%) did not obtain adequate pain control in the dose-titration phase. Thirteen patients were considered long-term successes with a mean follow-up of 16.7 months (range = 6.3 to 44 months). Nine patients failed to achieve adequate pain relief due to side effects or lack of efficacy. Fifty-nine percent of the patients successful in the dose-titration stage (42% of all patients considered) were considered long-term successes. Patients in the long-term phase maintained adequate pain control with minimal dose escalation. This study demonstrates the tolerability and effectiveness of intrathecal clonidine in the treatment of chronic pain. The physician using clonidine for long-term intrathecal infusion should be cognizant of the risk that severe rebound systemic hypertension can occur with abrupt cessation of the intrathecal infusion of clonidine.

A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain

To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50–150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95% −0.001, CI −3.36, P=0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline ( P=0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline ( n=5) had significantly ( P<0.05) better analgesia and overall outcome than did those on placebo ( n=6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.