A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain.

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Diagnosis and management of postherpetic neuralgia.

Risk factors for postherpetic neuralgia (PHN) include: increasing age; a prodrome of pain before rash onset; the degree of spread of the rash, particularly if it extends beyond a single dermatome; and severity of pain during the acute attack. Forty per cent of patients over 50 and 75% of those over 75 develop PHN following resolution of the rash. Patients develop persistent pain classified as PHN 120 days following rash onset. It can be either constant or paroxysmal and is commonly described as burning, stabbing or itching and located in the same dermatomal distribution as the shingles rash. Pain can lead to sleep disturbance, anorexia, reduced socialisation and reactive depression. Paracetamol should be tried initially for mild to moderate pain, either alone or in combination with codeine but there is no evidence to support the use of NSAIDs. Compared with other antidepressants, tricyclic antidepressants are the most likely to confer benefit in neuropathic pain. In frail elderly patients nortriptyline appears to be tolerated best. Both gabapentin and pregabalin can reduce pain and improve sleep patterns in patients with PHN. Patients with severe pain or those whose condition is affecting their daily activities and function should be referred to a specialist in pain management.

Towards a definition of refractory neuropathic pain for epidemiological research. An international Delphi survey of experts.

BACKGROUND: Best current estimates of neuropathic pain (NeuP) prevalence come from studies using various screening detecting pain with probable neuropathic features; the proportion experiencing significant, long-term NeuP, 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. METHODS: We report an international Delphi survey of experts in NeuP, aiming for consensus on the features required to define, for epidemiological research: (1) neuropathic pain; and (2) when NeuP is "refractory". A web-based questionnaire was developed and data collected from three rounds of questionnaires from nineteen experts. RESULTS: There was good consensus on essential inclusion of six items to identify NeuP ("prickling, tingling, pins & needles", "pain evoked by light touch", "electric shocks or shooting pain", "hot or burning" pain, "brush allodynia on self-examination", and "relevant history") and on some items that were non-essential. Consensus was also reached on components of a "refractory NeuP" definition: minimum duration (one year); number of trials of drugs of known effectiveness (four); adequate duration of these trials (three months / maximum tolerated); outcomes of treatment (pain severity, quality of life). Further work needs to validate these proposed criteria in general population research. CONCLUSIONS: This paper presents an international consensus on measuring the epidemiology of refractory neuropathic pain. This will be valuable in reaching an agreed estimate of the prevalence of neuropathic pain, and the first estimate of refractory neuropathic pain prevalence.

Long-term follow-up of patients undergoing laparoscopic surgery for phaeochromocytoma.

INTRODUCTION: Phaeochromocytomas are rare tumours with a recurrence after open surgery ranging between 6-23 per cent. Long-term follow-up studies after laparoscopic surgery for phaeochromocytoma are lacking. The aim of this study was to look at the long-term oncological outcome of a consecutive series of patients from a single centre undergoing laparoscopic surgery for a phaeochromocytoma. METHODS: Demographic data on all patients with an adrenal tumour or paraganglioma were prospectively kept on a database between September 1999 and December 2017. Electronic hospital records, including imaging from a national linked archiving and communication system, were reviewed for patients with a phaeochromocytoma in November 2021. RESULTS: During the study interval 135 patients with a phaeochromocytoma were operated on in the unit, of which 118 (87.4 per cent) were attempted laparoscopically. Five (4.2 per cent) were converted to open surgery, whereas 117 had a potentially curative operation. There was no peri- or postoperative mortality. At a median follow-up of 10 (interquartile range 6-12.9) years, only 3 (2.6 per cent) patients died from metastatic phaeochromocytoma. One further patient developed lymph node metastases, which were removed at open surgery. No patient had a local recurrence and the only significant predictor of recurrence was the presence of lymph node metastases (P < 0.001). Two patients developed a contralateral adrenal phaeochromocytoma, while one of these also had a paraganglioma. The Kaplan-Meier estimate of phaeochromocytoma-free survival was 96 per cent (95 per cent c.i. 92.2 to 98.8) at 5 years and 92 per cent (95 per cent c.i. 86.7 to 97.3) at 10 years. CONCLUSION: This study demonstrates that long-term oncological outcomes of laparoscopic surgery for patients with a phaeochromocytoma are at least as good as that with an open operation.

Relationships between changes in pain severity and other patient-reported outcomes: an analysis in patients with posttraumatic peripheral neuropathic pain.

BACKGROUND: The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain. METHODS: This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in pain (0-10 NRS) as the predictor and scores on the following PRO measures as the outcome: Pain Interference Index; Hospital Anxiety and Depression Scale anxiety and depression subscales; Medical Outcomes Study-Sleep Scale 9-item Sleep Problems Index and Sleep Disturbance subscale; and Daily Sleep Interference Scale (0-10 NRS). RESULTS: Change in pain severity showed clear, direct relationships with changes in function, anxiety, depression, and sleep PROs, all of which were statistically significant (P <.001). Results from subgroup analyses (≥30% or ≥50% pain responders, pregabalin or placebo treatment, age ≤ 51 years or > 51 years) tended to be consistent with results from the overall sample. CONCLUSIONS: Overall, a direct relationship exists between pain and various aspects of patient's well-being and functioning, which can provide a quantitative assessment of how improvements in pain may be expected to relate to other patient outcomes. (http://ClinicalTrials.gov Identifier number NCT00292188; EudraCT #2005-003048-78).

Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial.

BACKGROUND AND OBJECTIVE: Postherpetic neuralgia (PHN) and diabetic polyneuropathy (DPN) are two common causes of peripheral neuropathic pain. Typical localized symptoms can include burning sensations or intermittent shooting or stabbing pains with or without allodynia. Evidence-based treatment guidelines recommend the 5% lidocaine (lignocaine) medicated plaster or pregabalin as first-line therapy for relief of peripheral neuropathic pain. This study aimed to compare 5% lidocaine medicated plaster treatment with pregabalin in patients with PHN and patients with DPN. METHODS: The study was a two-stage, adaptive, randomized, controlled, open-label, multicentre trial that incorporated a drug wash-out phase of up to 2 weeks prior to the start of the comparative phase. At the end of the enrollment phase, patients who fulfilled the eligibility criteria were randomized to either 5% lidocaine medicated plaster or pregabalin treatment and entered the 4-week comparative phase. The interim analysis represents the first stage of the two-stage adaptive trial design and was planned to include data from the comparative phase for the first 150 randomized patients of the 300 total planned for the trial. Patients aged > or = 18 years with PHN or DPN were recruited from 53 investigational centres in 14 European countries. For this interim analysis, 55 patients with PHN and 91 with DPN (full-analysis set [FAS]), randomly assigned to the treatment groups, were available for analysis. Topical 5% lidocaine medicated plaster treatment was administered by patients to the area of most painful skin. A maximum of three or four plasters were applied for up to 12 hours within each 24-hour period in patients with PHN or DPN, respectively. Pregabalin capsules were administered orally, twice daily. The dose was titrated to effect: all patients received 150 mg/day in the first week and 300 mg/day in the second week of treatment. After 1 week at 300 mg/day, the dose of pregabalin was further increased to 600 mg/day in patients with high pain intensity scores. The pre-planned primary study endpoint was the rate of treatment responders, defined as completing patients experiencing a reduction from baseline of > or = 2 points or an absolute value of < or = 4 points on the 11-item numerical rating scale of recalled average pain intensity over the last 3 days (NRS-3), after 4 weeks of treatment. Secondary endpoints included > or = 30% and > or = 50% reductions in NRS-3 scores, changes in neuropathic pain symptom inventory (NPSI) scores and allodynia severity ratings. Overall, 65.3% of patients treated with the 5% lidocaine medicated plaster and 62.0% receiving pregabalin responded to treatment with respect to the primary endpoint. A higher proportion of PHN patients responded to plaster treatment compared with pregabalin (63.0% vs 37.5%), whereas in the larger DPN group treatments were comparable. Both treatments improved NPSI scores and reduced allodynia severity. Patients administering lidocaine plaster experienced fewer drug-related adverse events (3.9% vs 39.2%) and there were substantially fewer discontinuations due to drug-related adverse events (1.3% vs 20.3%). CONCLUSION: After 4 weeks, 5% lidocaine medicated plaster treatment was associated with similar levels of analgesia in patients with PHN or DPN but substantially fewer frequent adverse events than pregabalin.

The role of topiceuticals in cancer pain.

PURPOSE OF REVIEW: Pain is one of the most common and feared symptoms associated with a new diagnosis of cancer and its subsequent treatment. Unfortunately, it remains undertreated in around one third of patients. It has been recently postulated that one mechanism for this could be failure to recognize neuropathic pain. One attractive option in both the case of neuropathic pain and pain associated with intolerable side effects of prescribed opioids is the use of 'topiceuticals', as a means of targeted pain relief with potentially fewer side effects. The present review summarizes the evidence base for the various topiceuticals available for the treatment of localized neuropathic pain. RECENT FINDINGS: The recent evidence base for established treatments such as capsaicin and lignocaine is examined. A variety of novel and previously used therapies are considered. SUMMARY: The use of topiceuticals in localized neuropathic pain associated with malignancy remain a valuable option with many advantages over systemic treatments. In addition to anecdotal reports of efficacy, there is a growing body of evidence to consider the early use of topical lignocaine and capsaicin in this context. The authors' have proposed a guideline including the use of topiceuticals to aid in the management of neuropathic pain.

Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials.

BACKGROUND: Pregabalin is an effective treatment option for many patients with neuropathic pain. Higher doses of pregabalin have been shown to be more effective in improving pain outcomes but, in practice, failing to appropriately increase the dose can leave patients under-treated. METHODS: This was a pooled analysis of 6 flexible-dose clinical trials of pregabalin in patients with neuropathic pain (diabetic peripheral neuropathy, peripheral herpetic neuralgia, posttraumatic pain, or postsurgical pain). Patients were divided into "dose pathway" groups based on their weekly pregabalin dose from the start of their trial to the first week of their maintenance phase. These were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; 300 to 600 mg/day. Pain outcomes assessed for each group at each new dose were proportion of 30% and 50% responders (≥30% or ≥50% reduction in mean pain score from baseline) and mean change in pain score. Percent change in mean pain score from baseline was assessed using a marginal structural model. RESULTS: Seven hundred and sixty-one patients treated with flexible-dose pregabalin were included in the analysis. For each dose pathway group, there was a notably greater proportion of 30% and 50% responders and change in pain score, at each escalating dose. As assessed by the marginal structural model, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week. This dose response with flexible-dose pregabalin was consistent with that previously observed with fixed-dose pregabalin. CONCLUSION: Many patients who do not respond to lower doses of pregabalin will respond with notable improvements in pain outcomes when the dose is escalated. These data should encourage physicians treating patients with neuropathic pain to escalate pregabalin to the dose that delivers optimal analgesia and tolerable side effects.

Satisfaction, Adherence and Health-Related Quality of Life with Transdermal Buprenorphine Compared with Oral Opioid Medications in the Usual Care of Osteoarthritis Pain.

BACKGROUND: Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. METHODS: Patients in the UK with self-reported knee and/or hip OA who had been receiving one or more of TDB, co-codamol (an oral paracetamol/codeine combination) and tramadol for at least 1 month completed an online or telephone questionnaire. Medication satisfaction scores, HRQL scores (Short-Form 36 [SF-36]), medication adherence (Morisky Medication Adherence Scale [MMAS™]), adverse events and treatment discontinuations were recorded. Linear and logistic regression models were used to compare the treatment effect of TDB with co-codamol or tramadol. RESULTS: Overall, 966 patients met the inclusion criteria; 701 were taking only one of the target medications (TDB: 85; co-codamol: 373; tramadol: 243). The largest age group was 50-59 years and 76.0 % of patients were female. The TDB group was younger, with more male patients, therefore the statistical models were adjusted for age and sex. Medication satisfaction scores were significantly higher in the TDB group than the other two groups (TDB vs. co-codamol: 3.56, 95 % confidence interval [CI] 1.90-6.68, p < 0.0001; TDB vs. tramadol: 3.22, 95 % CI 1.67-6.20, p = 0.0005). Physical Component Summary scores for HRQL and mean adherence were also higher in the TDB group, while Mental Component Summary HRQL scores were similar across the three groups. CONCLUSIONS: Patients with knee and/or hip OA pain treated with TDB were more satisfied and more adherent with their medication, and reported higher Physical Component Summary HRQL scores than those treated with co-codamol or tramadol, although demographic differences were observed between groups.

The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized Neuropathic Pain, and Clinical Evidence Supporting its Use.

When peripheral neuropathic pain affects a specific, clearly demarcated area of the body, it may be described as localized neuropathic pain (LNP). Examples include postherpetic neuralgia and painful diabetic neuropathy, as well as post-surgical and post-traumatic pain. These conditions may respond to topical treatment, i.e., pharmaceutical agents acting locally on the peripheral nervous system, and the topical route offers advantages over systemic administration. Notably, only a small fraction of the dose reaches the systemic circulation, thereby reducing the risk of systemic adverse effects, drug-drug interactions and overdose. From the patient's perspective, the analgesic agent is easily applied to the most painful area(s). The 5% lidocaine-medicated plaster has been used for several years to treat LNP and is registered in approximately 50 countries. Many clinical guidelines recommend this treatment modality as a first-line option for treating LNP, particularly in frail and/or elderly patients and those receiving multiple medications, because the benefit-to-risk ratios are far better than those of systemic analgesics. However, some guidelines make only a weak recommendation for its use. This paper considers the positioning of the 5% lidocaine-medicated plaster in international treatment guidelines and how they may be influenced by the specific criteria used in developing them, such as the methodology employed by randomized, placebo-controlled trials. It then examines the body of evidence supporting use of the plaster in some prevalent LNP conditions. Common themes that emerge from clinical studies are: (1) the excellent tolerability and safety of the plaster, which can increase patients' adherence to treatment, (2) continued efficacy over long-term treatment, and (3) significant reduction in the size of the painful area. On this basis, it is felt that the 5% lidocaine-medicated plaster should be more strongly recommended for treating LNP, either as one component of a multimodal approach or as monotherapy.

A pharmacological treatment algorithm for localized neuropathic pain.

Neuropathic pain is caused by a lesion or disease affecting the somatosensory system and is difficult to manage, often proving refractory to existing treatments. In more than half of cases, it is localized and affects a specific, clearly circumscribed area of the body (localized neuropathic pain, or LNP). A recently developed screening tool enables patients with probable neuropathic pain/LNP to be identified quickly and easily. In view of the conflicting current treatment recommendations, an advisory board of pain specialists met in June 2015 to develop a complementary treatment guidance algorithm, for use in the primary care setting and by non-pain specialists. The starting point of the algorithm is a diagnosis of LNP and there was consensus that first-line treatment should be a topical analgesic agent, because the benefit/risk ratios are far better than for systemic agents. Topical application offers site-specific delivery, a lower total systemic dose and avoidance of first-pass metabolism, reducing the risk of adverse events and drug/drug interactions. The 5% lidocaine medicated plaster has most evidence supporting its use in LNP, producing effective analgesia and reducing the associated area of allodynia, but other topical agents include capsaicin, clonidine and botulinum toxin type A. Treatment should be commenced with the topical agent of choice, and the patient re-assessed after an appropriate period. Where the response is good the topical agent is continued, with a re-evaluation after 3-6 months. A systemic agent (e.g. gabapentin, pregabalin, duloxetine, venlafaxine) is added if there is only a partial response, or substituted if there is no response, and the patient re-assessed after a month. If there is poor or no response to the systemic agent the patient should be switched to an alternative one and, if this also proves ineffective, referred to a pain specialist.

Estimating the burden of disease in chronic pain with and without neuropathic characteristics: does the choice between the EQ-5D and SF-6D matter?

The EQ-5D and Short Form (SF)12 are widely used generic health-related quality of life (HRQoL) questionnaires. They can be used to derive health utility index scores, on a scale where 0 is equivalent to death and 1 represents full health, with scores less than zero representing states "worse than death." We compared EQ-5D or SF-6D health utility index scores in patients with no chronic pain, and chronic pain with and without neuropathic characteristics (NC), and to explore their discriminant ability for pain severity. Self-reported health and chronic pain status was collected as part of a UK general population survey (n=4451). We found moderate agreement between individual dimensions of EQ-5D and SF-6D, with most highly correlated dimensions found for mental health and anxiety/depression, role limitations and usual activities, and pain and pain/discomfort. Overall 43% reported full health on the EQ-5D, compared with only 4.2% on the SF-6D. There were significant differences in mean utilities for chronic pain with NC (EQ-5D 0.47 vs SF-6D 0.62) and especially for severe pain (EQ-5D 0.33 vs SF-6D 0.58). On the EQ-5D, 17% of those with chronic pain with NC and 3% without NC scored "worse than death," a state which is not possible using the SF-6D. Health utilities derived from EQ-5D and SF-12/36 can discriminate between group differences for chronic pain with and without NC and greater pain severity. However, the instruments generate widely differing HRQoL scores for the same patient groups. The choice between using the EQ-5D or SF-6D matters greatly when estimating the burden of disease.

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

Sativex is an endocannabinoid system modulator principally containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit.

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

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.

An investigation of constructions of justice and injustice in chronic pain: a Q-methodology approach.

This study used Q-methodology to explore justice-related accounts of chronic pain. Eighty participants completed the Q-sorting procedure (33 chronic pain sufferers and 47 non-pain sufferers). Analysis revealed five main factors. Three factors blame: society for poor medical and interpersonal treatment; the chronic pain sufferer for indulging in self-pity and unempathic healthcare workers for ignoring patients. A fourth factor acknowledges the unfairness of pain and encourages self-reliance. The fifth factor rejects injustice in the chronic pain discourse. Overall, there is a shared view that chronic pain brings unfair treatment, disrespect and a de-legitimization of pain. Future research ideas are suggested.

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

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 > or = 2 points or an absolute value of < or = 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.

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

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 patient's 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.

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 people's 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, people's 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.

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

OBJECTIVE: To compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial. SUMMARY BACKGROUND DATA: LA 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. METHODS: All 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. RESULTS: Two 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. CONCLUSIONS: There 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.