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Although one of the first pieces of legislation to address ethical issues in clinical trials was drawn up following the findings from the Nuremberg Trials, only in the more recent clinical research have the principles of beneficence, non-maleficence, autonomy and justice been considered and informed consent plays a major role. In the UK, the National Research Ethics Service and the Medicines and Healthcare Products Regulatory Agency require compliance with Good Clinical Practice. Patients are unlikely to participate in, or clinicians consent their patients to, trials where they do not feel safe or protected - data and safety monitoring assess for loss of clinical equipoise thus ensuring the most efficacious treatment is always available. Honesty and trust are crucial and place an obligation on investigators to disseminate even less favourable trial results, with the ultimate aim being partnerships between patients, their families, and those delivering the research which are mutually beneficial and respectful.

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

Michael Serpell,1 Mark Latymer,2 Mary Almas,3 Marie Ortiz,4 Bruce Parsons,4 Rita Prieto5 1University Department of Anaesthesia, Stobhill Ambulatory Care Hospital, Glasgow, 2Pfizer Ltd, Tadworth, UK; 3Pfizer, Groton, CT, 4Pfizer, New York, NY, USA; 5Pfizer GEP SLU, Madrid, Spain 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. Keywords: neuropathic pain, pregabalin, dosing

This study was funded by the Chief Scientist Office, part of the Scottish Government Health Directorates (CZH-4-429). Background: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. Methods : Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003–2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. Results : The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25–40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. Conclusions: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines, was common. Postprint

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.\ud \ud 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.\ud \ud 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.

Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.

Background: Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9‐tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15‐week randomized, double‐blind, placebo‐controlled parallel group study. Methods: In total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co‐primary efficacy endpoints were the 30% responder rate in PNP 0–10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated. Results: At the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention‐to‐treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05–3.70]. There was also a reduction in mean PNP 0–10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0–10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment. Conclusions: These findings demonstrate that, in a meaningful proportion of otherwise treatment‐resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.

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., 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.

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.

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.

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). Methods: Patients with a pain score ≥4 (0–10 scale) were randomized and treated with either flexible-dose pregabalin 150–600 mg/day (n = 127) or placebo (n = 127) in an 8-week double-blind treatment period preceded by a 2-week placebo run-in. Results: Pregabalin was associated with a significantly greater improvement in the mean end-point pain score vs. placebo; mean treatment difference was −0.62 (95% CI −1.09 to −0.15) (P = 0.01). The average pregabalin dose at end-point was ∼326 mg/day. Pregabalin was also associated with significant improvements from baseline in pain-related sleep interference, and the Medical Outcomes Study sleep scale sleep problems index and sleep disturbance subscale (all P

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 enrolment 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 ≥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 150mg/day in the first week and 300 mg/day in the second week of treatment. After 1week 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 ≥2 points or an absolute value of ≥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 ≥30% and ≥50% reductions in NRS-3 scores, changes in neuropathic pain symptom inventory (NPSI) scores and allodynia severity ratings. Results: 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.

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.

Background: Laparoscopic colorectal surgery has been claimed to enhance recovery when compared with open surgery. The aim of our study was to investigate whether laparoscopic colorectal resection improved recovery with the use of a multimodal rehabilitation programme. Method: We carried out a prospective audit of 80 patients undergoing elective colorectal resection between November 2003 and March 2005. All patients underwent a fast-track protocol with early feeding, mobilization and a fluid and sodium restriction regime. Recovery was measured in terms of return of gastrointestinal function, hospital stay, complications and quality of life measures. Results: Of the 80 patients in the study 22 underwent laparoscopic resection and 58 had open surgery. Patients were well matched for all baseline characteristics. The groups were not significantly different in terms of opioid or antiemetic use. They were also similar in median time to first flatus (69 h vs 69 h, P = 0.36) and median time to first bowel motion (127 h vs 101 h, P = 0.07). There was no difference in median hospital stay (5.8 days vs 5.9 days, P = 0.87) or complications (P = 0.46) between the laparoscopic and open group. There were no significant differences in Short Form 36 scores between the two groups for any of the components measured. Conclusion: Laparoscopic colorectal resection does not appear to reduce the duration of ileus or hospital stay with the use of a multimodal rehabilitation regime. Further large randomized trials are required to confirm these findings.

Research interest into alternatives to analgesic medication has grown substantially during the past two decades. Moreover, a number of studies have provided empirical evidence that music listening, and in particular listening to our own preferred music, may provide an emotionally engaging distraction capable of reducing both the sensation of pain itself and the accompanying negative affective experience. The current study is a survey of 318 chronic pain sufferers, which aimed to (i) give a detailed description of the music listening behaviour of this group and relate this to experience of pain and quality of life, and (ii) indicate the numbers who consider music listening to be part of their pain management and investigate their perceptions of the benefits. Results indicated distraction and relaxation to be the most frequently perceived benefits of music reported by participants. Both frequent music listening and a perception of music as personally important were further found to relate to higher quality of life. Also, personal importance of music was significantly related to listening to help pain. These findings suggest beneficial effects of music listening to long-term pain.

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.

This article reports two empirical experiments investigating the anxiety and pain reducing effects of listening to music via personal stereo following surgical procedures involving general anaesthetic. Both experiments involved participants selecting music of their own choice. In Experiment 1, following minor surgery on the foot, 20 participants in an experimental group listened to music while 20 participants in a control group did not. Results indicate that the music group felt significantly less anxiety than the control group. No differences in pain measurements between the two groups were found. Experiment 2 involved a music listening group of 30 females and a no music control group of 28 females. Both groups underwent a total abdominal hysterectomy. Post-operative measures of pain, anxiety and patient-controlled analgesia were taken. No differences between the groups were obtained on these measurements. The results of both experiments are discussed with reference to subjective responses to musical stimuli.

To compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial.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.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.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.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.

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.\ud \ud Design: Randomised, double blind, crossover trial of 14 weeks’ duration comparing dihydrocodeine and nabilone.\ud \ud Setting: Outpatient units of three hospitals in the United Kingdom.\ud \ud Participants: 96 patients with chronic neuropathic pain, aged 23-84 years.\ud \ud 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.\ud \ud 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.\ud \ud 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.\ud \ud 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.

Die Therapie des peripheren neuropathischen Schmerzes ist auch heutzutage eine schmerztherapeutische Herausforderung. Das Ziel, eine optimale medikamentose Wirkung-Nebenwirkung-Relation zu erzielen, ist Grundvoraussetzung fur die erwunschte Patientencompliance. Der Einsatz von Cannabis ist dabei eine oft diskutierte Medikamentenoption.

Background The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood. The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg. Methods Forty patients with similar preoperative characteristics were randomized, 20 to each group. Results There were no significant differences in intraoperative heart rate or cardiac index, although the latter fell significantly soon after insufflation in both groups. The fall in cardiac index lasted longer (7 versus 2 min) and coincided with a slower rise in mean arterial pressure in those having 15 mmHg insufflation. Changes in peak airway pressure, end-tidal carbon dioxide and arterial blood gases were similar. After operation the low-pressure group had significantly less pain, better preservation of pulmonary function and were discharged home sooner (P = 0.015). Conclusions Insufflation pressure significantly affects the haemodynamic changes and postoperative pain associated with laparoscopic cholecystectomy.

We examined the flow pattern produced when liquid dye was actively injected into a fluid medium at various flows through five different commonly used spinal needles. At all flows, the Whitacre-type needles produced a directional stream exiting at an angle from the longitudinal axis. At intermediate rates the stream developed tracks which disappeared at faster rates. The Quincke needle always produced an undeviated stream of dye and did not form tracks at any flow rate. When a perspex plate (representing the spinal cord) was interposed in front of the needle, the dispersion of dye was always unidirectional from the Whitacre needle and bidirectional from the Quincke needle. The dye adhered to the surface of the plate as a concentrated film at slow rates and at faster rates it dispersed turbulently for both types of needle.

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.

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.

A double-blind randomised clinical trial was undertaken in 40 patients undergoing major abdominal surgery. Postoperative pain relief was provided using epidural infusions of 0.06% bupivacaine with fentanyl 4 micrograms.ml-1 (n = 20) (group F) or with pethidine 1.5 mg.ml-1 (n = 20) (group P). Postoperative pain scores using a visual analogue scale (0-100 mm) were not significantly different between the two groups. Median pain scores were 0-19 mm at all times of assessment indicating that good analgesia was provided by both regimens. There was no significant difference between the epidural infusion rates in the two groups. The side effects and effect on pulmonary function were similar in each group. Nine patients were withdrawn from the study (four from group F, five from group P) due to failure of the epidural technique or other complications. Fourteen patients, equally distributed, required a total of 24 epidural 'top-ups' by an anaesthetist because of inadequate analgesia. We demonstrated no advantage with epidural pethidine over fentanyl when used by infusion in combination with bupivacaine in the management of postoperative pain.

A patient is presented who obtained only an L1 sensory block, which was inadequate for her procedure, from continuous spinal anaesthesia despite appropriate doses of 0.5% plain bupivacaine. She then developed a high spinal block after an epidural was sited and a test dose given in the sitting position. The possible mechanisms for this are discussed.

A new generation of Atraumatic (blunt tipped) needles now exists in addition to the traditional Quincke (cutting tip) needles for LP.We wished to identify the optimal size and type of needle that should be used for this technique. Requirements include rapid and accurate transduction of CSF pressure and adequate flow rate for CSF collection purposes while minimizing headache and other neurologic sequelae. Different types of available Atraumatic and Quincke needles were tested in two models that simulated normal and raised CSF pressures. The flow rates and the time required for an accurate transduction of CSF pressure onto a standard spinal manometer through each needle type was measured. Overall, Atraumatic-tipped needles compared favorably with similarly sized Quincke needles tested. The 20-gauge needles displayed suitable flow and pressure transduction characteristics. Some of the 22-gauge Atraumatic needles rapidly measured CSF pressure, but their flow rates were only suitable for small volume CSF collection. There is extensive literature to support that neurologic sequelae are reduced using Atraumatic needles. Diagnostic LP can be easily and accurately performed by using a large Atraumatic needle with the potential for considerable reduction in post-LP headache and related neurologic sequelae.NEUROLOGY 1996;47: 33-37

Carbon dioxide pneumoperitoneum has been shown to produce respiratory and hemodynamic changes due to both CO2 absorption and the effects of increased intraperitoneal pressure. We have measured the blood gas, end-tidal CO2, and hemodynamic changes produced during extraperitoneal CO2 insufflation (n = 22). These have been compared with the changes occurring during CO2 pneumoperitoneum (n = 11) under standardized anesthetic conditions. The changes observed during pneumoperitoneum were consistent with previous descriptions. There was a median rise in arterial pCO2 of 1 kPa over the first 15-20 min, followed by a second phase of only gradual change. There was also an increase in mean arterial pressure of 18 mmHg during the insufflation period. We have found a similar magnitude of rise in arterial pCO2 during extraperitoneal insufflation (median 0.83 kPa), but the rate of rise was significantly slower (P0.05). In addition, there was no change in the mean arterial pressure during extraperitoneal insufflation. Our results suggest that extraperitoneal CO2 insufflation may be safer than CO2 pneumoperitoneum in patients with preexisting cardiorespiratory disease.

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.

Perioperative haemodynamic changes are well recognised sequelae of adrenalectomy for phaeochromocytomas. The aim of this study was to compare haemodynamic changes in patients undergoing laparoscopic adrenalectomy (LA) for phaeochromocytomas and other adrenal tumours.Patients were identified from a prospective database (Jan 1999-Feb 2008). All patients were managed by a multi-disciplinary team. Haemodynamic variables were: pulse, blood pressure and the requirement of antihypertensive or vasopressor therapies in the perioperative period.Over the nine-year period, 34 consecutive patients underwent laparoscopic phaeochromocytoma resection (one patient had delayed contralateral LA) and 104 consecutive patients underwent LA for other tumours (two patients had delayed contralateral LA). 5 out of 35 resections in the phaeochromocytoma group experienced severe hypertension (systolic blood pressure (SBP)200 mm Hg) compared to two out of 106 resections in the non phaeochromocytoma group (p=0.010). No patient in either group had a transient or persistent (10 min) SBP220 mm Hg. Intraoperative antihypertensive use was significantly increased in the phaeochromocytoma group (p0.005). There were no significant differences between groups for persistent hypotension (SBP80 mm Hg), heart rate120/min and recovery room haemodynamic parameters.LA for phaeochromocytoma can be accomplished with low perioperative haemodynamic complications when compared to LA for other adrenal tumours.

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).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.EudraCT No. 2006-003132-29.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.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.

The processing of nociception involves multiple neural pathways, transmitters and receptors. All this suggests that there will never be a single ‘magic bullet’ analgesic drug. Optimum pain control will therefore require a multimodal approach using several analgesic therapies.

Interventional pain procedures have their own place in the treatment algorithm of resistant chronic pains. The advantages of these techniques are that they are usually a one-off treatment over a period of months and do not require maintenance therapy and, if effective, patient compliance is good.

The unpleasant sensation of pain plays an important protective role. Physiological, ‘fast’ pain warns us of imminent tissue damage and enables us to locate and withdraw from the source of injury. Later, inflammatory, ‘slow’ pain encourages protective immobilization of the injured area, which promotes tissue healing and functional recovery.

In order to prescribe for and treat painful conditions pharmacologically it is important to know whether the pain to be treated is nociceptive, neuropathic or mixed in nature. Neuropathic pain in particular may not respond to conventional analgesics. A simple and successful way to use analgesics in most pain conditions requires application of the World Health Organization (WHO) pain ladder [1] and use of multimodal analgesia. This chapter will focus on non-opioid, opioid and anti-neuropathic analgesic medications in current usage and will comment on their efficacy and safe prescription.

Background 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. Methods Eighty patients were randomized to restricted fluids (less than 2 litres water and 77 mmol sodium for 24 h after surgery) or a standard postoperative fluid regimen (3 litres water and 154 mmol sodium per day for as long as necessary). The primary endpoint was hospital stay. Results The median (i.q.r.) total intravenous fluid intake in the restricted group was 4·50 (4·00–5·62) litres compared with 8·75 (8·00–9·80) litres in the standard group (P < 0·001). Intravenous sodium intake was also significantly less in the restricted group (229 (131–332) versus 560 (477–667) mmol; P < 0·001). There was no difference in median time to first flatus (2·9 versus 2·9 days; hazard ratio (HR) 0·85 (95 per cent confidence interval (c.i.) 0·54 to 1·32); P = 0·466) or first bowel motion (4·7 versus 4·9 days; HR 1·06 (95 per cent c.i. 0·68 to 1·65); P = 0·802) between the restricted and standard groups, or in median hospital stay (7·2 versus 7·2 days; HR 1·03 (95 per cent c.i. 0·66 to 1·61); P = 0·902). Conclusion Restriction of postoperative intravenous fluid and sodium does not reduce hospital stay following elective colorectal surgery.

The important features which determine the ease of use of spinal needles include rapid detection of cerebrospinal fluid, minimal delay before injection and low resistance to injection of local anaesthetic. We investigated these three parameters among the following 11 spinal needles: Becton-Dickinson 22 G, 25 G and 27 G Whitacre, 25 G and 27 G Quincke; B. Braun Spinocan 22 G, 25 G and 26 G Quincke; Vygon 25 G Whitacre, Portex 26 G Pencil Point and the 24 G Sprotte. Three needles of each type were tested using an artificial cerebrospinal fluid model maintained at body temperature and at two hydrostatic pressures of 12 and 50 cm of water. The Becton Dickinson 27 G Whitacre has an immediate detection time at both pressure heights, a reasonably short 'ready to inject' time and relatively low resistance to injection, which, together with a reported low rate of postdural puncture headache, would indicate that it is the most appropriate for spinal anaesthesia. The 25 G Whitacre types would be the next most suitable to use.