Michael Serpell

Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial

&NA; A double‐blind, randomised, placebo‐controlled 8‐week study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain, using doses up to 2400 mg/day. The study used a novel design that was symptom‐ rather than syndrome‐based; an approach that aimed to reflect the realities of clinical practice. Participants had a wide range of neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. Patients were randomised to gabapentin (n=153) or placebo (n=152). Gabapentin was given in three divided doses, initially titrated to 900 mg/day over 3 days, followed by two further increases, to a maximum of 2400 mg/day if required by the end of week 5. The primary outcome measure was changed in average daily pain diary score (baseline versus final week). Over the 8 week study, this score decreased (i.e. improved) by 1.5 (21%) in gabapentin treated patients and by 1.0 (14%) in placebo treated patients (P=0.048, rank‐based analysis of covariance). Significant differences were shown in favour of gabapentin (P<0.05) for the Clinician and Patient Global Impression of Change, and some domains of the Short Form‐McGill Pain Questionnaire. Improvements were also shown in patient‐reported outcomes in quality of life, as seen by significant differences in favour of gabapentin in several domains of the Short‐Form‐36 Health Survey. Gabapentin was well tolerated and the majority of patients completed the study (79 versus 73% for placebo). The most common adverse events were mild to moderate dizziness and somnolence, most of which were transient and occurred during the titration phase. This study shows that gabapentin reduces pain and improves some quality‐of‐life measures in patients with a wide range of neuropathic pain syndromes.

Randomized clinical trial of the effect of postoperative intravenous fluid restriction on recovery after elective colorectal surgery

Use of intravenous fluids is an important part of perioperative management. The aim of this study was to compare outcome following administration of restricted or standard postoperative intravenous fluids and sodium in patients undergoing elective colorectal surgery.

5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study

ABSTRACT Objective: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). Study design and methods: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of ≥2 points or an absolute value of ≤4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs). Results: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. Conclusion: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study

Objective To compare the analgesic efficacy and side effects of the synthetic cannabinoid nabilone with those of the weak opioid dihydrocodeine for chronic neuropathic pain. Design Randomised, double blind, crossover trial of 14 weeks’ duration comparing dihydrocodeine and nabilone. Setting Outpatient units of three hospitals in the United Kingdom. Participants 96 patients with chronic neuropathic pain, aged 23-84 years. Main outcome measures The primary outcome was difference between nabilone and dihydrocodeine in pain, as measured by the mean visual analogue score computed over the last 2 weeks of each treatment period. Secondary outcomes were changes in mood, quality of life, sleep, and psychometric function. Side effects were measured by a questionnaire. Intervention Patients received a maximum daily dose of 240 mg dihydrocodeine or 2 mg nabilone at the end of each escalating treatment period of 6 weeks. Treatment periods were separated by a 2 week washout period. Results Mean baseline visual analogue score was 69.6 mm (range 29.4-95.2) on a 0-100 mm scale. 73 patients were included in the available case analysis and 64 patients in the per protocol analysis. The mean score was 6.0 mm longer for nabilone than for dihydrocodeine (95% confidence interval 1.4 to 10.5) in the available case analysis and 5.6 mm (10.3 to 0.8) in the per protocol analysis. Side effects were more frequent with nabilone. Conclusion Dihydrocodeine provided better pain relief than the synthetic cannabinoid nabilone and had slightly fewer side effects, although no major adverse events occurred for either drug. Trial registration Current Controlled Trials ISRCTN15330757.

Comparison of lumbar plexus block versus conventional opioid analgesia after total knee replacement

A randomised controlled study was undertaken to assess the analgesic efficacy of continuous lumbar plexus block for the first 48 hours after total knee replacement surgery. Boluses of 0.5% bupivacaine with adrenaline 1 in 200 000 (0.3 ml/kg) were administered through a cannula inserted into the neurovascular sheath of the femoral nerve. Thirteen patients who received this block required significantly less morphine than a control group of 16 patients. Pain scores were similar and there were no complications related to this technique.

Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy

ABSTRACT Objective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patients satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs. Clinical trial registration: EudraCT No. 2006-003132-29. Results: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients’ treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated. Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

Neuropathic pain in the community: More under-treated than refractory?

Summary There is a significant proportion of chronic pain that is persistent and neuropathic, appears undertreated or untreated, and is associated with poor health and quality of life. Abstract Best current estimates of neuropathic pain prevalence come from studies using screening tools detecting pain with probable neuropathic features; the proportion experiencing significant, long‐term neuropathic pain, and the proportion not responding to standard treatment are unknown. These “refractory” cases are the most clinically important to detect, being the most severe, requiring specialist treatment. The aim of this study was to estimate the proportion of neuropathic pain in the population that is “refractory,” and to quantify associated clinical and demographic features. We posted self‐administered questionnaires to 10,000 adult patients randomly selected from 10 general practitioner practices in 5 UK locations. The questionnaire contained chronic pain identification and severity questions, cause of pain, SF‐12, EQ‐5D, S‐LANSS (Self‐administered Leeds Assessment of Neuropathic Signs and Symptoms), PSEQ (Pain Self‐Efficacy Questionnaire), use of neuropathic pain medications, and health care utilisation. These data were combined to determine the presence and characteristics of “refractory” neuropathic pain according to the defining features identified by a Delphi survey of international experts. Graded categories of chronic pain with and without neuropathic characteristics were generated, incorporating the refractory criteria. Completed questionnaires were returned by 4451 individuals (response rate 47%); 399 had “chronic pain with neuropathic characteristics” (S‐LANSS positive, 8.9% of the study sample); 215 (53.9%) also reported a positive relevant history (“Possible neuropathic pain”); and 98 (4.5% of all Chronic Pain) also reported an “adequate” trial of at least one neuropathic pain drug (“Treated possible neuropathic pain”). The most refractory cases were associated with dramatically poorer physical and mental health, lower pain self‐efficacy, higher pain intensity and pain‐related disability, and greater health care service use.

Pregabalin in the treatment of post-traumatic peripheral neuropathic pain: a randomized double-blind trial.

Background:  Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated pregabalin in the treatment of post‐traumatic peripheral neuropathic pain (including post‐surgical).

Local or general anesthesia for open hernia repair: a randomized trial

ObjectiveTo compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial. Summary Background DataLA hernia repair is thought to be safer for patients, causes less postoperative pain, cost less, and is associated with a more rapid recovery when compared with the same operation performed under GA. MethodsAll patients presenting to three surgeons during the study period with a primary groin hernia were considered eligible. Outcome parameters measured including tests of vigilance, divided attention, sustained attention, memory, cognitive function, pain, return to normal activity, and costs. ResultsTwo hundred seventy-nine patients were randomized to LA or GA hernia repair; 276 of these had an operation, with 138 participants in each group. At 6, 24, and 72 hours postoperatively there were no differences in vigilance or divided attention between the groups. Similarly, memory, sustained attention, and cognitive function were not impaired in either group. Although physical activity was significantly impaired at 24 hours, this and return to usual social activities were similar in both groups. While patients in the LA group had significantly less pain on moving, at 6 hours they were less likely to recommend the same operation to someone else. GA hernia repair cost 4% more than the same operation under LA. ConclusionsThere are no major differences in patient recovery after LA or GA hernia repair. Patients should be offered a choice of anesthesia, LA or GA, for repair of their groin hernia.

Comparison of psychological and physical function in neuropathic pain and nociceptive pain: Implications for cognitive behavioral pain management programs

Research has increased our understanding of the psychological and physical functioning associated with persistent pain and has facilitated the development of cognitive behavioral pain management programs to help improve peoples physical function and decrease their distress in the presence of persistent pain. The majority of this research has focused on nociceptive pain or pain of mixed etiology. There has been less focus on these aspects of neuropathic pain. It is possible that differences exist in the function and difficulties associated with nociceptive and neuropathic pain. These differences may be associated with our clinical observation that some people with neuropathic pain have difficulty applying some aspects of the theory and practice of cognitive behavioral pain management. The purpose of this study was to compare a single neuropathic pain condition (post‐herpetic neuralgia) with a persistent pain of nociceptive origin (low back pain) and determine whether differences exist in: (1) physical and psychological function; (2) factors that increase difficulties; (3) responses to pain; (4) beliefs about pain and (5) problems experienced. The results suggest that the differences between the two groups were not on the major variables of pain, mood, cognition and physical function. The main differences were in factors that increase pain, peoples responses to pain, their beliefs about diagnosis and the cause of pain and the problems they reported as a result of experiencing pain. The implications of our findings for the development of cognitive behavioral pain management programs for people with neuropathic pain are discussed.