Volume 7, Issue 1

Background and aims The experience of pain may vary in accordance with personality traits and individual characteristics. Neuroticism is demonstrated to constitute a vulnerability factor among younger and middle-aged pain patients. The combination of openness and neuroticism is associated with high anxiety/depression scores among adult individuals with chronic conditions. The aim of this study was to investigate possible associations between pain and the personality dimensions of neuroticism, extroversion, openness, agreeableness and conscientiousness among persons aged 60 years and older. An additional aim was to explore whether such associations are equally gender expressed. Methods The Swedish National Study on Aging and Care includes a randomly selected sample from the National Population Register. The data collection was conducted at four research centres and was approved by the Ethics Committees of Lund University and the Karolinska Institutet, Stockholm, Sweden. The Blekinge sample includes 1402 individuals, aged 60–96 years, of whom 769 (55%) reported pain. A total of 2312 individuals had been invited to participate. The reason for non-participation was registered. Participants underwent medical examination and testing by research personnel, conducted in two sessions, each of which lasted about 3 h. A questionnaire was completed between the two sessions. Pain was self-reported and based on the question: Have you had ache/pain during the last 4 weeks? Information on personality traits was obtained by means of the personality SGC1 questionnaire; a 60-item Swedish version of Costa & McCrae’s FFM questionnaire. Personality traits were then tested based on gender by means of multivariate forward logistic regression in models adjusted for age, insomnia, financial status and educational level. Results When adjusting for covariates among women, neuroticism had a small but significant odds ratio of experiencing pain (OR 1.05, CI 1.02–1.08). Insomnia had the highest odds ratio (OR 2.19, CI 1.52–3.15) followed by low education (OR 1.59, CI 1.07–2.36), while belonging to the younger part of the older adult cohort was also associated with pain (OR 1.02, CI 1.005–1.04). In men, neuroticism (OR 1.03, CI 1.002–1.06) followed by openness (OR 1.03 CI 1.001–1.07) had a small but significant odds ratio of experiencing pain. Insomnia had the highest odds ratio (OR 1.98, CI 1.24–3.15). Conclusions Personality traits and pain were related among the older adults but there were gender differences. The relationship between pain and neuroticism in women was about the same in strength as the relation between pain and neuroticism/openness in men. Both sexes suffer from insomnia. The relationship between personality traits and pain was only affected to a minor extent by insomnia. Implications There is a need to increase awareness of the impact of personality as well as to provide improved treatment for pain and insomnia in older people.

Background and aims We have previously reported that sinomenine, an alkaloid isolated from the root of the plant Sinomenium acutum , had antinociceptive effect in rodent models of acute inflammatory or neuropathic pain. As a traditional medicine, sinomenine is used in China to treat rheumatoid arthritis (RA). Methods In the present study, we evaluated the potential antinociceptive effect of sinomenine in a mouse model of RA, collagen type II antibody (CII Ab) induced arthritis (CAIA) after acute and chronic administration. Results As single administration, sinomenine at 40 or 80 mg/kg significantly reduced mechanical hypersensitivity both at the time of peak joint inflammation (days 11–19 after CII Ab injection) or during the post-inflammatory phase (days 35–54). No tolerance to the effect of 80 mg/kg sinomenine was observed during repeated injection twice a day for 5 days from day 11 to day 19 or from day 49 to day 53 after CII Ab injection in CAIA mice. Conclusions We have shown that sinomenine is effective in alleviating localized and spread hypersensitivities in CAIA mice both during acute inflammation and in post-inflammatory phase. Further, repeated sinomenine administration has elevated the baseline mechanical threshold without producing tolerance. Implications Sinomenine may be clinically useful to treat chronic pain in RA, including wide-spread pain which appears to be a difficult clinical problem despite the improvement in the acute treatment of RA by disease modifying agents.

Background and aims The present randomized open label parallel group study was conducted to evaluate if an oral oxycodone (OXY) regimen can be at least equally effective and as safe for postoperative analgesia after caesarean section (CS) as a standard of care program using nurse-administered intravenous morphine (IVM), followed by oral codeine. Methods Eighty women (40 + 40) were scheduled for elective CS under spinal anaesthesia. All patients received postoperative multimodal analgesic therapy, including ibuprofen and paracetamol. The OXY group got standardized extended release and short acting oral treatment (and in a few cases intravenous OXY) as needed and the other group received current standard of care, IVM as needed for 24 h, followed by codeine. Opioid treatment lasted maximum five days. Outcome measures were pain intensity (numerical rating scale, NRS), opioid requirements, duration of administering opioids and safety for mother and newborn. All opioids in the study were expressed in OXY equivalents, using a conversion table. As the bioavailability of each opioid has a certain extent of interindividual bioavailability this conversion represents an approximation. The possible influence of opioids on the newborns was evaluated by the Neurological Adaptive Capacity Score at birth and at 24 and 48 h. Results During the first 24 h, there were no differences between treatments in opioid requirements or mean pain intensity at rest but pain intensity when asking for rescue medication was lower in the OXY than in the IVM group (mean ± SD; 5.41 ± 6.42 vs. 6.42 ± 1.61; p = 0.027). Provoked pain (uterus palpation) during the first 6h was also less in the OXY group (3.26 ± 2.13 vs. 4.60 ± 2.10; p = 0.007). During the 25–48 h period postoperatively, patients on OXY reported significantly lower pain intensity at rest (2.9 ± 1.9 vs. 3.8 ± 1.8; p = 0.039) and consumed less opioids (OXY equivalents; mg) (31.5 ± 9.6 vs. 38.2 ± 38.2; p = 0.001) than those on IVM/codeine. The total amount of opioids 0–5 days postoperatively was significantly lower in the OXY than in the IVM/codeine group (108.7 ± 37.6 vs. 138.2 ± 45.1; p = 0.002). Duration of administering opioids was significantly shorter in the OXY group. Time to first spontaneous bowel movement was shorter in the OXY group compared with the IVM/codeine group. No serious adverse events were recorded in the mothers but the total number of common opioid adverse effects was higher among women on IVM/codeine than among those receiving OXY (15 vs. 3; p = 0.007). No adverse outcomes in the newborns related to treatment were observed in either group. Conclusions In a multimodal protocol for postoperative analgesia after CS better pain control and lower opioid intake was observed in patients receiving oral OXY as compared to those on IVM/codeine. No safety risks for mother and child were identified with either protocol. Implications Our findings support the view that use of oral OXY is a simple, effective and time saving treatment for postoperative pain after CS.

Background and aims Bone marrow aspiration and/or biopsy (BMAB), performed under local anaesthesia in adults, is a common and often painful procedure. Anxiety is known to intensify pain during the procedure. Nitrous oxide (N 2 O), known for its sedative and analgesic benefit in various short medical procedures and labour pain, could be advantageous also for pain relief during bone marrow examination. N 2 O acts rapidly and is eliminated in a couple of minutes once the inhalation is stopped, and occasional side effects (e.g. dizziness and nausea) are mild. The aim of this study was to compare the analgesic effects of inhaled 50% mixture of nitrous oxide and oxygen to 50% oxygen during bone marrow examination. Methods In this randomized, controlled, patient and observer blinded study patients received either 50% mixture of nitrous oxide and oxygen or 50% mixture of oxygen in air during bone marrow examination, in addition to local analgesia. Both patient groups comprised 35 adult patients. Pre-procedural anxiety and procedural pain were rated on the Numeral Rating Scale (NRS 0‒10). Cognitive function was measured before and 30 min after the procedure. Possible side effects were recorded. A telephone interview was performed 24 h later. Results There were no statistically significant differences in pain scores of the procedural steps (median NRS ranging 3.0‒4.0) between the study groups. High pain scores of 8‒10 comprised 0% vs. 8.6% of the scores during infiltration, 2.9% vs. 5.7% during puncture, 11.4% vs. 14.3% during aspiration and 2.9% vs. 2.9% during biopsy in N 2 O and 50% O 2 groups, respectively (NS). Pre-procedural anxiety (median NRS 3.5 in both groups), measured in the outpatient clinic just prior to procedure, correlated with pain intensity during bone marrow aspiration (P = 0.045). There were no significant differences between side effects. During the BMAB four patients (3 in N 2 O group, 1 in 50% O 2 group) reported dizziness and one patient in the N 2 O group reported nausea. Gas inhalation did not affect the cognitive function of the participants. In both groups the majority (>80%) of the patients was satisfied with the inhalation technique. During the 24 h interview, most of the participants were pain free and they did not report any serious adverse effects. Conclusions In spite of similar moderate to strong procedural pain in both groups and no benefit of N 2 O, most patients were satisfied with the inhalational techniques. We assume that the bedside presence of an anaesthesiologist and the distraction caused by the inhalational arrangements introduced positive context-sensitive therapeutic effect independent of the gas used. Pre-procedural anxiety predicted pain associated with bone marrow aspiration. Implications Inhaled 50% nitrous oxide was not an effective analgesic during bone marrow examination in our unselected outpatient population. Further studies should concentrate on its use with patients predicted to be at increased risk of suffering intense pain during the procedure, such as very anxious patients or those who have a painful history of previous bone marrow examinations.

Background and aims The development of postoperative chronic pain (POCP) after surgery is a major problem with a considerable socioeconomic impact. It is defined as pain lasting more than the usual healing, often more than 2–6 months. Recent systematic reviews and meta-analyses demonstrate that the N -methyl- D -aspartate-receptor antagonist ketamine given peri- and intraoperatively can reduce immediate postoperative pain, especially if severe postoperative pain is expected and regional anaesthesia techniques are impossible. However, the results concerning the role of ketamine in preventing chronic postoperative pain are conflicting. The aim of this study was to perform a systematic review and a pooled analysis to determine if peri- and intraoperative ketamine can reduce the incidence of chronic postoperative pain. Methods Electronic searches of PubMed, EMBASE and Cochrane including data until September 2013 were conducted. Subsequently, the titles and abstracts were read, and reference lists of reviews and retrieved studies were reviewed for additional studies. Where necessary, authors were contacted to obtain raw data for statistical analysis. Papers reporting on ketamine used in the intra- and postoperative setting with pain measured at least 4 weeks after surgery were identified. For meta-analysis of pain after 1, 3, 6 and 12 months, the results were summarised in a forest plot, indicating the number of patients with and without pain in the ketamine and the control groups. The cut-off value used for the VAS/NRS scales was 3 (range 0–10), which is a generally well-accepted value with clinical impact in view of quality of life. Results Our analysis identified ten papers for the comprehensive meta-analysis, including a total of 784 patients. Three papers, which included a total of 303 patients, reported a positive outcome concerning persistent postsurgical pain. In the analysis, only one of nine pooled estimates of postoperative pain at rest or in motion after 1, 3, 6 or 12 months, defined as a value ≥3 on a visual analogue scale of 0–10, indicated a marginally significant pain reduction. Conclusions Based on the currently available data, there is currently not sufficient evidence to support a reduction in chronic pain due to perioperative administration of ketamine. Only the analysis of postoperative pain at rest after 1 month resulted in a marginally significant reduction of chronic postoperative pain using ketamine in the perioperative setting. Implications It can be hypothesised, that regional anaesthesia in addition to the administration of perioperative ketamine might have a preventive effect on the development of persistent postsurgical pain. An additional high-quality pain relief intra- and postoperatively as well after discharge could be more effective than any particular analgesic method per se. It is an assumption that a low dose infusion ketamine has to be administered for more than 72 h to reduce the risk of chronic postoperative pain.

Background and aims Pain is a subjective experience, and as such, pre-clinical models of human pain are highly simplified representations of clinical features. These models are nevertheless critical for the delivery of novel analgesics for human pain, providing pharmacodynamic measurements of activity and, where possible, on-target confirmation of that activity. It has, however, been suggested that at least 50% of all pre-clinical data, independent of discipline, cannot be replicated. Additionally, the paucity of “negative” data in the public domain indicates a publication bias, and significantly impacts the interpretation of failed attempts to replicate published findings. Evidence suggests that systematic biases in experimental design and conduct and insufficiencies in reporting play significant roles in poor reproducibility across pre-clinical studies. It then follows that recommendations on how to improve these factors are warranted. Methods Members of Europain, a pain research consortium funded by the European Innovative Medicines Initiative (IMI), developed internal recommendations on how to improve the reliability of pre-clinical studies between laboratories. This guidance is focused on two aspects: experimental design and conduct, and study reporting. Results Minimum requirements for experimental design and conduct were agreed upon across the dimensions of animal characteristics, sample size calculations, inclusion and exclusion criteria, random allocation to groups, allocation concealment, and blinded assessment of outcome. Building upon the Animals in Research: Reportingin vivo Experiments (ARRIVE) guidelines, reporting standards were developed for pre-clinical studies of pain. These include specific recommendations for reporting on ethical issues, experimental design and conduct, and data analysis and interpretation. Key principles such as sample size calculation, a priori definition of a primary efficacy measure, randomization, allocation concealments, and blinding are discussed. In addition, considerations of how stress and normal rodent physiology impact outcome of analgesic drug studies are considered. Flow diagrams are standard requirements in all clinical trials, and flow diagrams for preclinical trials, which describe number of animals included/excluded, and reasons for exclusion are proposed. Creation of a trial registry for pre-clinical studies focused on drug development in order to estimate possible publication bias is discussed. Conclusions More systematic research is needed to analyze how inadequate internal validity and/or experimental bias may impact reproducibility across pre-clinical pain studies. Addressing the potential threats to internal validity and the sources of experimental biases, as well as increasing the transparency in reporting, are likely to improve preclinical research broadly by ensuring relevant progress is made in advancing the knowledge of chronic pain pathophysiology and identifying novel analgesics. Implications We are now disseminating these Europain processes for discussion in the wider pain research community. Any benefit from these guidelines will be dependent on acceptance and disciplined implementation across pre-clinical laboratories, funding agencies and journal editors, but it is anticipated that these guidelines will be a first step towards improving scientific rigor across the field of pre-clinical pain research.

Background and purpose Dealing with chronic pain is difficult and affects physiological as well as psychological well-being. Patients with chronic pain are often reporting concurrent emotional problems such as low mood and depressive symptoms. Considering this, treatments need to involve strategies for improving mood and promoting well-being in this group of patients. With the rise of the positive psychology movement, relatively simple intervention strategies to increase positive feelings, cognitions, and behaviours have become available. So far, the evidence for positive psychology techniques mainly comes from studies with healthy participants, and from studies with patients expressing emotional problems such as depression or anxiety as their main complaint. This study describes an initial attempt to explore the potential effects of a positive psychology intervention in a small sample of patients suffering from chronic pain. Methods A replicated single case design was employed with five participants. The participants started to fill out daily self-reports and weekly questionnaires two weeks before the intervention started, and continued throughout the intervention. In addition, they filled out a battery of questionnaires at pretest, posttest, and at a three months follow-up. The instruments for assessment were selected to cover areas and constructs which are important for pain problems in general (e.g. disability, life satisfaction, central psychological factors) as well as more specific constructs from positive psychology (e.g. compassion, savoring beliefs). Results The results on pre and post assessments showed an effect on some of the measures. However, according to a more objective measure of reliable change (Reliable Change Index, RCI), the effects were quite modest. On the weekly measures, there was a trend towards improvements for three of the participants, whereas the other two basically did not show any improvement. The daily ratings were rather difficult to interpret because of their large variability, both between and within individuals. For the group of participants as a whole, the largest improvements were on measures of disability and catastrophizing. Conclusions The results of this preliminary study indicate that a positive psychology intervention may have beneficial effects for some chronic pain patients. Although it is not to be expected that a limited positive psychology intervention on its own is sufficient to treat pain-related disability in chronic patients, our findings suggest that for some it may be an advantageous complement to enhance the effects of other interventions. Implications The results of this pilot study about the potential effects of a positive psychology intervention for chronic pain patients may be encouraging, warranting a larger randomized controlled study. Future studies may also concentrate on integrating positive psychology techniques into existing treatments, such as composite CBT-programs for chronic pain patients. Our advice is that positive psychology interventions are not to be regarded as stand-alone treatments for this group of patients, but may potentially enhance the effect of other interventions. However, when and for which patients these techniques may be recommended is to be explored in future research.