Average Daily Pain Score Research Articles

Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: a prospective randomized trial

Our hypothesis was that in patients undergoing shoulder arthroplasty, a prospective randomized trial would find no significant differences in average daily pain scores of those treated with interscalene nerve block (INB) vs. local liposomal bupivacaine (LB). Sixty patients undergoing primary shoulder arthroplasty were assessed for eligibility. Study arms included either intraoperative local infiltration of LB (20 mL bupivacaine/20 mL saline) or preoperative INB, with a primary outcome of postoperative average daily visual analog scale scores for 4 days. Secondary outcomes assessed included opioid consumption, length of stay, and complications. Randomization was by a computerized algorithm. Only the observer was blinded to the intervention. Three patients were excluded, all before randomization. A total of 57 patients were analyzed. Outcomes showed a significant increase in pain in the LB group between 0 and 8 hours postoperatively (mean [standard deviation] 5.3 [2.2] vs. 2.5 [3.0]; P = .001). A significant increase in intravenous morphine equivalents was found in the INB group at 13 to 16 hours (mean [standard deviation] 1.2 [0.9] vs. 0.6 [0.7]; P = .01). No significant differences were found in any variable after postoperative day 0 between the 2 groups. An increase in early postoperative pain on the day of surgery was found with LB, whereas the INB group required more narcotics at the end of the day. After the day of surgery, there were no significant differences found in any variables. These findings suggest that LB provides similar overall pain relief as INB, with no increase in complications or length of stay and a decrease in narcotic requirements on the day of surgery.

The Effect of Gabapentin Enacarbil on Pain Associated with Moderate-to-Severe Primary Restless Legs Syndrome in Adults: Pooled Analyses from Three Randomized Controlled Trials.

Adults with moderate-to-severe primary restless legs syndrome (RLS) often experience painful dysesthesias, which may lead to impaired quality of life. The aim of this study was to assess the effects of gabapentin enacarbil (GEn) on pain associated with moderate-to-severe primary RLS in adults. Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials (NCT00298623, NCT00365352, NCT01332305) for adults receiving GEn or placebo once daily. Change in average daily RLS pain score and a combined International Restless Legs Scale (IRLS)-pain response were examined. The modified intention-to-treat population included 671 adults (placebo, n=244; GEn 600mg, n=161; GEn 1200mg, n=266). Both GEn doses significantly improved average daily RLS pain score at week 12 (p<0.001 for GEn 600mg vs. placebo and GEn 1200mg vs. placebo). The combined IRLS-pain response subanalysis included 366 patients with a baseline IRLS total score ≥15 and pain score ≥4 (placebo, n = 133; GEn 600mg, n = 86; GEn 1200mg, n=147). Most patients were both IRLS and pain responders (placebo, 40%; GEn 600mg, 70%; GEn 1200mg, 67%). Spearman rank correlations between IRLS total and pain score (change from baseline to week 12) were moderate or strong. The most frequent treatment-emergent adverse events were somnolence (placebo, 5%; GEn 600mg, 20%; GEn 1200mg, 23%) and dizziness (placebo, 4%; GEn 600mg, 13%; GEn 1200mg, 22%). This post hoc pooled analysis suggests that GEn (600 and 1200mg) once daily significantly improved pain associated with moderate-to-severe primary RLS in adults; however, the analysis was not powered to detect statistical differences between the two GEn doses. Numerically, more GEn-treated patients had a combined IRLS-pain response than placebo-treated patients.

Rapid Recovery Pathway After Spinal Fusion for Idiopathic Scoliosis.

Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is associated with significant pain and prolonged hospitalization. There is evidence that early mobilization and multimodal analgesia can accelerate functional recovery and reduced length of stay (LOS). Using these principles, we implemented a quality improvement initiative to enable earlier functional recovery in our AIS-PSF population. We designed and implemented a standardized rapid recovery pathway (RRP) with evidence-based management recommendations for children aged 10 to 21 years undergoing PSF for AIS. Our primary outcome, functional recovery, was assessed using statistical process control charts for LOS and average daily pain scores. Our process measures were medication adherence and order set utilization. The balancing measure was 30-day readmission rate. We included 322 patients from January 1, 2011 to June 30, 2015 with 134 (42%) serving as historical controls, 104 (32%) representing our transition population, and 84 (26%) serving as our RRP population. Baseline average LOS was 5.7 days and decreased to 4 days after RRP implementation. Average daily pain scores remained stable with improvement on postoperative day 0 (3.8 vs 4.9 days) and 1 (3.8 vs 5 days) after RRP implementation. In the second quarter of 2015, gabapentin (91%) and ketorolac (95%) use became routine and order set utilization was 100%. Readmission rates did not increase as a result of this pathway. Implementation of a standardized RRP with multimodal pain management and early mobilization strategies resulted in reduced LOS without an increase in reported pain scores or readmissions.

Is There a Benefit for Liposomal Bupivacaine Compared to a Traditional Periarticular Injection in Total Knee Arthroplasty Patients With a History of Chronic Opioid Use?

BackgroundPostoperative pain after total knee arthroplasty (TKA) poses a major challenge. It delays mobilization, increases opioid consumption and side effects, and lengthens hospitalization. This challenge multiplies when treating an opioid-dependent population. We examined whether a novel suspended release local anesthetic, liposomal bupivacaine (LB) would improve pain control and decrease opioid consumption after TKA compared to a standard periarticular injection in opioid-dependent patients. MethodsThirty-eight patients undergoing TKA were randomly assigned to receive either a periarticular injection (PAI) with LB (n = 20) or with a standard PAI (including a combination of ropivacaine, clonidine, Toradol, Epinepherine, and saline; n = 18) as part of a multimodal pain management approach. All periarticular injections were done by a single surgeon. Perioperative treatment was similar between groups. Postoperative information regarding pain level was evaluated by a pain visual analog scale score. Postoperative opioid consumption was recorded. ResultsAfter controlling baseline narcotic usage before surgery, no differences were found between groups in daily postoperative narcotic usage (P = .113), average daily pain score (P = .332), or maximum daily pain score (P = .881). However, when examining pain levels separately for each day, pain visual analog scale scores were reported higher in post operative day 1 in the LB group (P = .033). ConclusionsLB was not found to be superior to standard PAI in opioid-dependent patients undergoing TKA. This patient population continues to present a challenge even with modern multimodal pain protocols.

Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain

Mirogabalin (DS-5565) is an α2δ-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Nonlinear mixed-effects analyses were performed on average daily pain and on the incidence of the adverse events dizziness and somnolence. These models were used to predict the dose of mirogabalin equivalent to pregabalin and the probability of meaningful reduction in pain compared with placebo and pregabalin. In addition, regimen effects were evaluated for reductions of adverse events. Mirogabalin was estimated to be 17-fold more potent than pregabalin. The effectiveness of 150 mg pregabalin, dosed twice daily, attenuated by week 5. Therefore, the estimated mechanism-based equivalent dose (ED) of 17.7 mg mirogabalin was higher than that predicted to achieve comparable pain reduction. If attenuation of the pregabalin effect is real, mirogabalin doses lower than the ED could yield comparable pain reduction, albeit with less differentiation in pain from placebo. The incidence rate of dizziness and somnolence decreased over time. Twice-daily dosing of mirogabalin was predicted to yield a lower incidence rate of dizziness than once-daily dosing; thus, titration of dosages should reduce adverse event rates. These model results were used to influence phase 3 dosing selection.

(438) A 24-week extension of an open-label, long-term safety study evaluating the safety and effectiveness of once-daily, single-entity, hydrocodone in patients with chronic nonmalignant and non-neuropathic pain

HYD is a once-daily, single-entity hydrocodone bitartrate tablet formulated with abuse-deterrent properties that is under development for treatment of moderate-to-severe chronic pain. This 24-week extension of a long-term, open-label study with a 12-month maintenance period characterized the safety, effectiveness, and impact on quality of life (QoL) measures of HYD (20, 40, 60, 80, 120 mg/day) treatment in patients with moderate-to-severe chronic non-malignant and non-neuropathic pain. Evaluations included adverse events (AEs), aberrant drug behaviors, audiologic and clinical laboratory assessments, ECGs, average daily pain scores, the Brief Pain Inventory, the Short Form-36, and the MOS-Sleep-revised.

A randomized placebo-controlled trial of duloxetine for central pain in multiple sclerosis.

Pain is common in multiple sclerosis (MS). Duloxetine has a potential therapeutic role in treating MS-related pain. Thirty-eight MS patients were randomized 1:1 to receive duloxetine (n = 18) or matched placebo (n = 20). The dosing regimen was 30 mg daily for 1 week, then 60 mg daily for 5 weeks. The primary outcome measure was change in worst pain for week 6 relative to baseline recorded on a daily pain diary. Of 38 randomized patients, 14 (78%) patients randomized to duloxetine and 18 (90%) randomized to placebo completed treatment per protocol. These participants had an average age of 55.5 years, 25% were male, and 66% had relapsing-remitting MS (RRMS). Baseline characteristics were similar. Discontinuations were due primarily to drug intolerance. Among those who completed treatment, worst pain at 6 weeks was reduced by 29% (±20%) for duloxetine versus 12% (±18%) for placebo (P = .016). Average daily pain at 6 weeks was reduced by 39% (±29%) in the duloxetine group compared to 10% (±18.8%) in the placebo group (P = .002). There were no significant changes (week 6 vs. baseline) or between-group differences for subject global impression, Beck Depression Inventory, 36-item Short Form Health Status Survey (SF-36), or sleep quality score. Fewer patients could tolerate duloxetine compared to placebo. Among patients who completed 6 weeks of treatment, there were significant reductions in average and worst daily pain scores with duloxetine compared to placebo. This study suggests that duloxetine has a direct pain-relieving effect in MS.

Laparoscopic Donor Nephrectomy and Primary Post-Operative Pain Control Therapy.

The purpose of this study was to understand the outcomes associated with the use of ketorolac compared to standard analgesic therapy post laparoscopic donor nephrectomy (LDN). This was an IRB approved, single center, retrospective cohort analysis utilizing chart review. Subjects were identified using our institution's kidney donor list and the electronic medical record system. Subjects 18 years and older who underwent a LDN between November 1, 2007 and July 31, 2012 at our institution, who received at least one dose of intravenous (IV) opioid analgesics or IV ketorolac post-operatively, and with sufficient electronic records of patient-controlled analgesia (PCA) data available were included in the study and categorized to an opioid only group or a ketorolac plus opioid group. Data were collected utilizing paper and electronic medical records and the United Network for Organ Sharing database. The primary endpoint was opioid analgesic requirements per day while on PCA following LDN reported in intravenous morphine equivalents. Secondary endpoints included time to first stool, time to diet initiation during hospitalization, time to discharge, average daily pain score, change in estimated creatinine clearance using the CKD-EPI equation, bleeding events, naloxone usage, readmission rates, and mortality within the first year following procedure. Average cumulative opioid requirements while on PCA reported in IV morphine equivalents was 104 mg in the opioid only group (n=39) compared to 106 mg in the ketorolac plus opioid group (n=28). There was no difference in average daily pain scores on post-operative days 1-3. There was no difference in serum creatinine or creatinine clearance using the CKD-EPI equation at one year post kidney donation. Average hospital length of stay was similar between the two groups (4.3 days in both groups).Table: No Caption available.In this single-center, retrospective analysis, the use of ketorolac as an adjunctive analgesic therapy following a laparoscopic donor nephrectomy resulted in no difference in opioid requirements, kidney function at one year, or hospital length of stay. Additional randomized, prospective studies are needed to further assess safety and efficacy of ketorolac after kidney donation.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study

Objective:Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design.Research design and methods:This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330–495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep.Clinical trial registration:ClinicalTrials.gov identifier: NCT01271933.Results:A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan–Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported ‘benefit from treatment’ (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%).Conclusions:Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Postoperative opioid analgesic use after Nuss versus Ravitch pectus excavatum repair

Background/PurposeAnticipated postoperative pain may affect procedure choice in patients with pectus excavatum. This study aims to compare postoperative pain in patients undergoing Nuss and Ravitch procedures. MethodsA 5year retrospective review was performed. Data on age, gender, Haller index, procedure, pain scores, pain medications, and length of hospital stay were collected. Total inpatient opioid administration was converted to morphine equivalent daily dose per kilogram (MEDD/kg) and compared between procedures. ResultsOne hundred eighty-one patients underwent 125 (69%) Nuss and 56 (31%) Ravitch procedures. Ravitch patients were older (15.7 yo vs 14.6 yo, p=0.004) and had a higher Haller index (5.21 vs 4.10, p=<0.001). Nuss patients had higher average daily pain scores, received 25% more opioids (MEDD/kg 0.66 vs. 0.49, p=<0.001), and received twice as much IV diazepam/kg. In the multivariate analysis, higher MEDD/kg correlated with both the Nuss procedure and older age in the Nuss group. Opioid administration did not correlate with Haller index or Nuss bar fixation technique. Increased NSAID administration did not correlate with lower use of opioids. ConclusionThe Nuss procedure is associated with greater postoperative pain compared to the Ravitch procedure. Opioid use is higher in older patients undergoing the Nuss procedure, but is not associated with severity of deformity.

The association of vibratory sense and muscle strength with the incidence and worsening of knee instability: the most study

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S377 ECGs and vital signs were unremarkable and similar across all treatments. Plasma TCA concentration across the FX006 doseswere linear and dose-dependent. Peak plasma concentrations achieved with 40 mg TCA IR were 10X of those seen with FX006 40 mg. Conclusions: It is demonstrated that sustained residency of TCA in the joint prolongs therapeutic effect. The 40 mg dose of FX006 produced an effect atWeek 12 ( 3.7) that was equivalent to the maximal effect of TCA IR at Week 4. Surprisingly, between Weeks 2 and 11, the analgesic effect of the 40mg dose of FX006 exceeded themaximal effect of TCA IR seen at Week 4. This observation suggests that prolonged occupation of the corticosteroid receptor may be associated with an enhanced analgesic effect. Further, this amplification of effect may constitute a meaningful clinical improvement relative toTCA IR as indicated by the 20% responder analysis for the 40 mg dose of FX006. A study is underway to determine the TCA concentrations in the joint at varying time points, and subsequent studies against placebo will define effect size and duration of action. Figure 1. Weekly Mean of Average Daily Pain Score (ADP) Figure 2. Proportion of Responders, >20% Improvement

The Effects of Gastroretentive Gabapentin (Gralise®) on Spinal Stenosis Patients with Radicular Pain

Background: The health and efficacy profiles of Gralise® in the treatment of pain from spinal stenosis and radicular symptomatology have not been measured. A review of the current literature indicates that no studies exist that evaluate the safety and efficacy profiles of Gralise® in the treatment of pain from spinal stenosis and radicular symptomatology. Objective: Our study is aimed at determining whether Gralise is a safe and effective pharmacotherapy for the pain from spinal stenosis and radicular symptomatology. Study Design: A 4-week prospective open label single arm and single center study of patients with MRI diagnosis of spinal stenosis with radicular pain. Methods: The primary measure of efficacy was a change in average daily pain (ADP) score from baseline to completion of Gralise therapy for 4 weeks. The secondary efficacy endpoints were the patients’ Patients Global Impression of Change Scale (PGIC), the clinician’s Clinical Global Impression of Change Scale (CGI) reports, and the Medical Outcomes Study (MOS) sleep scale of improvement from baseline to completing 4 weeks of Gralise therapy. The safety and tolerability were evaluated by the incidence of adverse events reported while on Gralise therapy. Setting: The study was performed at the Clinical Research Facilities at Tulane Medical Center, New Orleans, Louisiana, in the period from December 1, 2012, to August 30, 2013. Results: Thirty-five patients achieved an efficacy point of one-week Gralise medication treatment. Twenty-seven of 35 (77.2%) patients completed all 5 visits. The PGIC noted a significant positive change in: (1) activity limitations; (2) symptoms; (3) emotions and overall quality of life when related to their condition from first visit as well as improved degree of change when related to their condition from first to last visit. The MOS sleep scale and sleep diaries noted a significant increase of hours slept on average (an increase in over one hour per night — 5.8 hours versus 6.86 hours) from the beginning of the study to the end. The CGI noted a majority of 10 out of 27 with marked significant therapeutic effect with no side effects. The ADP rating from pain intensity scale and pain diaries noted significant improvement of lesser levels of pain experienced (P =.5907 and P =.8547 respectively). No significant adverse effects were noted in the study. Limitations: Variation in degree of spinal stenosis, small sample size. Conclusions: Gralise demonstrated moderate efficacy with reduced pain intensity and increased sleep and was well tolerated in spinal stenosis patients with radicular symptoms. Key words: Spinal stenosis, gabapentin, Gralise®, radicular pain, neuropathic pain

Is there an alternative to continuous opioid infusion for neonatal pain control? A preliminary report of parent/nurse‐controlled analgesia in the neonatal intensive care unit

Continuous opioid infusion (COI) remains the mainstay of analgesic therapy in the neonatal intensive care unit (NICU). Parent/nurse-controlled analgesia (PNCA) has been accepted as safe and effective for pediatric patients, but few reports include use in neonates. This study sought to compare outcomes of PNCA and COI in postsurgical neonates and young infants. Twenty infants treated with morphine PNCA were retrospectively compared with 13 infants treated with fentanyl COI in a Midwestern pediatric hospital in the United States. Outcome measures included opioid consumption, pain scores, frequency of adverse events, and subsequent methadone use. The PNCA group (median 6.4 μg · kg(-1) · h(-1) morphine equivalents, range 0.0-31.4) received significantly less opioid (P < 0.001) than the COI group (median 40.0 μg · kg(-1) · h(-1) morphine equivalents; range 20.0-153.3), across postoperative days 0-3. Average daily pain scores (based on 0-10 scale) were low for both groups, but median scores differed nonetheless (0.8 PNCA vs 0.3 COI, P < 0.05). There was no significant difference in the frequency of adverse events or methadone use. Results suggest PNCA may be a feasible and effective alternative to COI for pain management in postsurgical infants in the NICU. Results also suggest PNCA may provide more individualized care for this vulnerable population and in doing so, may potentially reduce opioid consumption; however, more studies are needed.

The Cleveland Clinic experience with supraclavicular and popliteal ambulatory nerve catheters.

Continuous peripheral nerve blocks (CPNB) are commonly used for intraoperative and postoperative analgesia. Our study aimed at describing our experience with ambulatory peripheral nerve catheters. After Institutional Review Board approval, records for all patients discharged with supraclavicular or popliteal catheters between January 1, 2009 and December 31, 2011 were reviewed. A licensed practitioner provided verbal and written instructions to the patients prior to discharge. Daily follow-up phone calls were conducted. Patients either removed their catheters at home with real-time simultaneous telephone guidance by a member of the Acute Pain Service or had them removed by the surgeon during a regular office visit. The primary outcome of this analysis was the incidence of complications, categorized as pharmacologic, infectious, or other. The secondary outcome measure was the average daily pain score. Our study included a total of 1059 patients with ambulatory catheters (769 supraclavicular, 290 popliteal). The median infusion duration was 5 days for both groups. Forty-two possible complications were identified: 13 infectious, 23 pharmacologic, and 6 labeled as other. Two patients had retained catheters, 2 had catheter leakage, and 2 had shortness of breath. Our study showed that prolonged use of ambulatory catheters for a median period of 5 days did not lead to an increased incidence of complications.

Safety and Efficacy of Once-Daily Gastroretentive Gabapentin in Patients with Postherpetic Neuralgia Aged 75 Years and Over

BackgroundTreatment of postherpetic neuralgia (PHN) is more complicated in elderly patients, and multiple daily dosing, complex titration, and high incidences of adverse events can be limiting for many pharmacological treatment options.ObjectiveThe aim of this study was to determine whether the efficacy and tolerability of once-daily gastroretentive gabapentin (G-GR) is similar between elderly patients (≥75 years) and younger patients (<75 years).MethodsData from two phase III, placebo-controlled studies of 1,800 mg G-GR once daily with dinner in patients with PHN were integrated and analyzed by age subgroups (<75 years, n = 527; ≥75 years, n = 192). Efficacy assessments at endpoint (week 10) included baseline-adjusted change in average daily pain (ADP) and average daily sleep interference (SIS) scores, the proportion of responders (≥30 % pain reduction), and the proportion of patients feeling “Much” or “Very Much” improved on the Patient Global Impression of Change (PGIC).ResultsCompared with placebo, patients in both age subgroups treated with G-GR (placebo/G-GR) had greater reductions in mean ADP (≥75: −21.9/−34.2 %, p = 0.0348; <75: −29.9/−38.3 %, p = 0.0079) and SIS (≥75: −1.3/−2.4, p = 0.0017; <75: −1.8/−2.7, p < 0.0001), more patients were responders (≥75: 30.4/52.0 %, p = 0.0025; <75: 45.0/54.7 %, p = 0.0265), and more felt “Much” or “Very Much” improved on the PGIC (≥75: 20.7/35.0 %, p = 0.0272; <75: 33.6/44.9 %, p = 0.0077). The most common (placebo/G-GR) adverse events (AEs) were dizziness (≥75: 3.3/12.0 %; <75: 1.8/10.4 %), nausea (≥75: 1.0/5.4 %; <75: 2.9/4.2 %), and somnolence (≥75: 0/5.0 %; <75: 3.7/4.2 %). For all patients, AEs rapidly decreased to low steady levels after 4–5 weeks of treatment. The incidence of serious AEs was low and they were reported more frequently in the placebo than in the G-GR group.ConclusionsTherapy with once-daily G-GR was as effective for treating pain associated with PHN in elderly patients as it was in younger patients. G-GR was well tolerated, and the incidence of the most common AEs did not appear to be age related.

Meta-analysis of gabapentin in the treatment of postherpetic neuralgia

Objective To evaluate the effects and tolerability of gabapentin in the treatment of postherpetic neuralgia (PHN). Methods The randomized controlled trials (RCTs) of gabapentin for the treatment of PHN were retrieved from PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Chinese Biology Medicine (CBM), VIP, China National Knowledge Infrastructure (CNKI) and Wanfang Data. Two reviewers independently evaluated the quality of the included articles and abstracted the data. Meta-analysis was performed using RevMan 5.0. Results According to the enrollment criteria, 5 prospective, randomized controlled clinical trials including 1225 subjects were finally selected. The mean changes for average daily pain score were significant in gabapentin group compared with placebo group (SMD = -0.920, 95%CI: -1.330~-0.520; P = 0.000), as well as the mean change for Short-Form McGill Pain Questionnaire (SF-MPQ) visual analogue scale (SMD = -2.650, 95%CI: -3.410~-1.890; P = 0.000) and average daily sleep intervention score (SMD = -2.480, 95%CI: -3.750~-1.200; P = 0.000). There was no significance between gabapentin group and placebo group in the withdrawl rate (P > 0.05). The common adverse reactions during gabapentin treatment included dizziness (OR = 3.710, 95%CI: 2.530-5.430; P = 0.000), somnolence (OR = 2.430, 95%CI: 1.530-3.860; P = 0.000) and peripheral edema (OR = 13.570, 95%CI: 4.190-43.970; P = 0.000). Conclusion It is indicated clinically that gabapentin is effective and well tolerated for the treatment of postherpetic neuralgia with high retention rate. However, adverse reactions, such as dizziness, somnolence and edema, should be paid attention.

A pilot trial of intravenous pamidronate for chronic low back pain

Intravenous (i.v.) bisphosphonates relieve pain in conditions such as Paget’s disease of bone, metastatic bone disease, and multiple myeloma. Based on positive findings from a prior case series, we conducted a randomized placebo-controlled study to assess the analgesic effect of i.v. pamidronate in subjects with chronic low back pain (CLBP) and evidence of degenerative disease of the spine. Four groups of 11 subjects (7 active, 4 placebo) were enrolled at escalating dose levels of 30, 60, 90, and 180mg pamidronate (the latter administered as two 90mg infusions). Primary outcomes were safety and change from baseline in average daily pain scores, recorded at 1, 2, 3, and 6months postinfusion using electronic diaries. Secondary outcomes included responder rate, daily worst pain, and pain-related interference with daily function. There were no pamidronate-related serious adverse events or other significant safety findings. A statistically significant overall treatment difference in pain scores was observed, with clinically meaningful effects persisting for 6months in the 180mg pamidronate group. Least squares mean changes in daily average pain score were −1.39 (SE=0.43) for placebo, and −1.53 (0.71), −1.26 (0.81), −1.42 (0.65), and −4.13 (0.65) for pamidronate 30, 60, 90, and 180mg, respectively (P=0.012 for pamidronate 180mg vs placebo). The proportion of responders, changes in worst pain, and pain interference with daily function were also significantly improved for pamidronate 180mg compared with placebo. In conclusion, i.v. pamidronate, administered as two 90mg infusions, decreased pain intensity for 6months in subjects with CLBP.

Efficacy and Safety of Carisbamate in Patients with Diabetic Neuropathy or Postherpetic Neuralgia: Results from 3 Randomized, Double‐Blind Placebo‐Controlled Trials

The results of 3 proof-of-concept studies to evaluate carisbamate's efficacy and safety in treating neuropathic pain are presented. In studies 1 (postherpetic neuralgia, n=91) and 2 (diabetic neuropathy, n=137), patients received carisbamate 400mg/day or placebo for 4weeks and then crossed over to the other treatment for 4weeks. In study 3 (diabetic neuropathy, higher carisbamate doses), patients (n=386) were randomized (1:1:1:1) to receive either carisbamate 800mg/day, 1200mg/day, pregabalin 300mg/day or placebo for 15weeks. Primary efficacy end point was the mean of the last 7 average daily pain scores obtained on days the study drug was taken, for all 3 studies. Least square mean (95% CI) differences between carisbamate and placebo groups on the primary end point were as follows: study 1: -0.512 (-1.32, 0.29) carisbamate 400mg/day; study 2: -0.307 (-0.94, 0.33) carisbamate 400mg/day; and study 3: -0.51 (-1.10, 0.08), carisbamate 800mg/day; -0.55 (-1.13, 0.04), carisbamate 1200mg/day; and -0.43 (-1.01, 0.15), pregabalin 300mg/day. Neither carisbamate (all 3 studies) nor pregabalin (study 3) significantly differed from placebo, although multiple secondary end points showed significant improvement in efficacy with carisbamate in studies 1 and 2. Dizziness was the only treatment-emergent adverse event occurring at ≥10% difference in carisbamate groups versus placebo (study 1: 12% vs. 1%; study 3: 14% vs. 4%; study 2: 1% vs. 2%). Carisbamate, although well tolerated, did not demonstrate efficacy in neuropathic pain across these studies, nor did the active comparator pregabalin (study 3).

Predictive value of lidocaine for treatment success of oxcarbazepine in patients with neuropathic pain syndrome.

IntroductionPharmacotherapy in patients with neuropathic pain syndromes (NPS) can be associated with long periods of trial and error before reaching satisfactory analgesia. The aim of this study was to investigate whether a short intravenous (i.v.) infusion of lidocaine may have a predictive value for the efficacy of oxcarbazepine.MethodsIn total, 16 consecutive patients with NPS were studied in a prospective, uncontrolled, open-label study design. Each patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term oral oxcarbazepine treatment (900–1,500 mg/day). During an observation period of 28 days, treatment response was documented by a questionnaire including the average daily pain score documented on a numeric rating scale (NRS).ResultsA total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine treatment due to side effects. In an interim analysis predictive value of the lidocaine infusion was low with a Kendall’s tau correlation coefficient of 0.29 and coefficient of determination R2 of 0.119 (95% confidence interval –0.29 to 0.72). As a consequence of this low correlation, the study was discontinued for ethical reasons.ConclusionIn conclusion, lidocaine infusion has a low predictive value for effectiveness of oxcarbazepine—if at all.

A Negative Correlation Between Hyperalgesia and Analgesia in Patients with Chronic Radicular Pain: Is Hydromorphone Therapy a Double-Edged Sword?

Background: Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Yet, unconfirmed evidence suggests that chronic exposure to opioids may cause hypersensitivity to pain, a phenomenon known as opioid-induced hyperalgesia (OIH). Objectives: The current preliminary prospective study was aimed to explore the relationship between experimental OIH and clinical opioid induced analgesia (OIA) in a model of experimental OIH in patients with chronic radicular pain using intermediate-term opioid therapy. Study Design: Prospective evaluation Setting: Interdisciplinary Pain Clinic at a referral Health Care Campus Methods: Thirty patients with chronic neuropathic (radicular) pain were assessed prior to and following 4 weeks of an individually titrated dose of oral hydromorphone treatment (4-20 mg/d). The assessments included an evaluation of experimental OIH by testing for heat pain intensity and cold pain tolerance and an assessment of OIA by completing pain and disability questionnaires. Results: Hydromorphone was found to induce hyperalgesia, as measured by an elevation of phasic heat pain intensity (P &lt; 0.05). At the same time, hydromorphone caused significant clinical analgesic effects. There was a notable reduction in average daily pain scores (primary analgesic outcome) of 26 Visual Analog Scale (0-100) points. A significant negative correlation was found between OIH and all OIA measures (r = -0.389, P &lt; 0.05 for the primary analgesic outcome). Hydromorphone dosage was positively correlated with OIH (P &lt; 0.01, r = 0.467) and negatively correlated with OIA parameters (r = -0.592, P &lt; 0.01 for the primary analgesia outcome). Limitations: The nonrandomized, open-label, prospective evaluation. Conclusion: A 4-week regimen of open-label hydromorphone therapy results in a dosedependent OIH, which negatively correlates with its analgesic effect. Future randomized, controlled, and blinded studies are needed to verify these preliminary results. Key words: Opioid-induced hyperalgesia (OIH), analgesia, hydromorphone, neuropathic pain, disc herniation, radiculopathy