Pain chronification: what should a non-pain medicine specialist know?

Objective: Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of “pain chronification”.

Methods: This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification.

Results: Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: “Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification.”

Conclusions: Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.     

Detection of counterfeit Viagra with Raman spectroscopy

During the last few years, counterfeiters have become increasingly sophisticated by falsifying drugs and making them look identical to genuine tablets. In this paper, Raman spectroscopy is proposed as a fast and reliable method for the detection of counterfeit Viagra tablets. This technique can easily differentiate genuine from counterfeit tablets without the need of sample preparation. In total 18 tablets were analysed which all contained the active ingredient sildenafil, but different excipients were used, as could be observed in the Raman spectra between 1150 and 700 cm(-1). So, the spectra could be divided into genuine or counterfeit. Additionally, principal component analysis (PCA), combined with hierarchical cluster analysis (HCA), was used to establish an automated approach for the discrimination of counterfeit from genuine Viagra tablets. Raman spectroscopy, combined with principal components analysis, could be used in the future by customs or in the field to identify counterfeit tablets on the spot without involvement of trained chemists.     

Headache service quality: evaluation of quality indicators in 14 specialist-care centres

Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. Fifteen patients with M-TMD and 15 age- and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0–100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. Dopamine in plasma differed significantly between patients with M-TMD (4.98 ± 2.55 nM) and healthy controls (2.73 ± 1.24 nM; P < 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P < 0.001) and had lower PPTs (P < 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P < 0.05) and perceived mental stress (r = 0.34, n = 28, P < 0.05). The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.     

Pain in pancreatic ductal adenocarcinoma: A multidisciplinary,International guideline for optimized management

Abdominal pain is an important symptom in most patients with pancreatic ductal adenocarcinoma (PDAC). Adequate control of pain is often unsatisfactory due to limited treatment options and significant variation in local practice, emphasizing the need for a multidisciplinary approach. This review contends that improvement in the management of PDAC pain will result from a synthesis of best practice and evidence around the world in a multidisciplinary way. To improve clinical utility and evaluation, the evidence was rated according to the GRADE guidelines by a group of international experts. An algorithm is presented, which brings together all currently available treatment options. Pain is best treated early on with analgesics with most patients requiring opioids, but neurolytic procedures are often required later in the disease course. Celiac plexus neurolysis offers medium term relief in a substantial number of patients, but other procedures such as splanchnicectomy are also available. Palliative chemotherapy also provides pain relief as a collateral benefit. It is stressed that the assessment of pain must take into account the broader context of other physical and psychological symptoms. Adjunctive treatments for pain, depression and anxiety as well as radiotherapy, endoscopic therapy and neuromodulation may be required in selected patients. There are few comparative studies to help define which combination and order of these treatment options should be applied. New pain therapies are emerging and could for example target neural transmitters. However, until better methods are available, management of pain should be individualized in a multidisciplinary setting to ensure optimal care.     

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience

IntroductionAlthough deep brain stimulation (DBS) is effective for treating a number of neurological and psychiatric indications, surgical and hardware-related adverse events (AEs) can occur that affect quality of life. This study aimed to give an overview of the nature and frequency of those AEs in our center and to describe the way they were managed. Furthermore, an attempt was made at identifying possible risk factors for AEs to inform possible future preventive measures.Materials and MethodsPatients undergoing DBS-related procedures between January 2011 and July 2020 were retrospectively analyzed to inventory AEs. The mean follow-up time was 43 ± 31 months. Univariate logistic regression analysis was used to assess the predictive value of selected demographic and clinical variables.ResultsFrom January 2011 to July 2020, 508 DBS-related procedures were performed including 201 implantations of brain electrodes in 200 patients and 307 implantable pulse generator (IPG) replacements in 142 patients. Surgical or hardware-related AEs following initial implantation affected 40 of 200 patients (20%) and resolved without permanent sequelae in all instances. The most frequent AEs were surgical site infections (SSIs) (9.95%, 20/201) and wire tethering (2.49%, 5/201), followed by hardware failure (1.99%, 4/201), skin erosion (1.0%, 2/201), pain (0.5%, 1/201), lead migration (0.52%, 2/386 electrode sites), and hematoma (0.52%, 2/386 electrode sites). The overall rate of AEs for IPG replacement was 5.6% (17/305). No surgical, ie, staged or nonstaged, electrode fixation, or patient-related risk factors were identified for SSI or wire tethering.ConclusionsMajor AEs including intracranial surgery–related AEs or AEs requiring surgical removal or revision of hardware are rare. In particular, aggressive treatment is required in SSIs involving multiple sites or when Staphylococcus aureus is identified. For future benchmarking, the development of a uniform reporting system for surgical and hardware-related AEs in DBS surgery would be useful.     

Ethical implications of regenerative medicine in orthopedics: an empirical study with surgeons and scientists in the field

Background contextRegenerative medicine (RM) interventions, such as (stem) cell transplantation, scaffolds, gene transfer, and tissue engineering, are likely to change the field of orthopedics considerably. These strategies will significantly differ from treatments in current orthopedic practice, as they treat the underlying cause of disease and intervene at a biological level, preferably in an earlier stage. Whereas most of the RM interventions for orthopedics are still in the preclinical phase of research, the number of clinical studies is expected to increase rapidly in the future. The debate about the challenging scientific and ethical issues of translating these innovative interventions into (early) clinical studies is developing. However, no empirical studies that have systematically described the attitudes, opinions, and experiences of experts in the field of orthopedic RM concerning these challenges exist.PurposeThe aim of this study was to identify ethical issues that experts in the area of RM for musculoskeletal disorders consider to be relevant to address so as to properly translate RM interventions into (early) clinical studies.Study design/settingIn-depth qualitative interviews were conducted with 36 experts in the field, mainly spine surgeons and musculoskeletal scientists from The Netherlands and the United Kingdom.MethodsA topic list of open questions, based on existing literature and pilot interviews, was used to guide the interviews. Data analysis was based on the constant comparative method, which means going back and forth from the data to develop codes, concepts, and themes.ResultsFour ethical themes emerged from the interview data. First, the risks to study participants. Second, the appropriate selection of study participants. Third, setting relevant goal(s) for measuring outcome, varying from regenerating tissue to improving well-being of patients. Finally, the need for evidence-based medicine and scientific integrity, which is considered challenging in orthopedics.DiscussionThe overall attitude toward the development of RM was positive, especially because current surgical treatments for spine disorders lack satisfactory effectiveness. However, efforts should be taken to adequately address the ethical and scientific issues in the translation of RM interventions into clinical research. This is required to prevent unnecessary risks to study participants, to prevent exposure of future patients to useless clinical applications, as well as to prevent this young field from developing a negative reputation. Not only will the orthopedic RM field benefit from ethically and scientifically sound clinical studies, but the rise of RM also provides an opportunity to stimulate evidence-based practice in orthopedics and address hype- and profit-driven practices in orthopedics.     

Clarifying assent in pediatric research

Assent is a relatively young term in research ethics, but became an often mentioned ethical requirement in current pediatric research guidelines. Also, the European Society of Human Genetics considers assent an important condition for the inclusion of children in biobanks. However, although many emphasize the importance of assent, few explain how they understand the concept and few have elaborated on the underlying grounds. In this paper, we will discuss the different underlying ethical principles of assent. In the first category, assent appears to be derived from informed consent. This understanding is grounded in respect for autonomy and protection against harm. We conclude that this interpretation of assent is not of added value as a majority of children cannot be considered competent to make autonomous decisions. In addition, other safeguards are more appropriate to protect children against harm. The grounds from the second category can be classified as engagement grounds. These grounds do justice to the specifics of childhood and are of added value. Furthermore, we argue that it follows that both the content and the process of assent should be adjusted to the individual child. This can be referred to as personalized assent. Personalized assent is an appeal to the moral responsibility and integrity of the researcher.     

Homocysteine Exposure Affects Early Hemodynamic Parameters of Embryonic Chicken Heart Function

Maternal hyperhomocysteinemia has been associated with an increased risk of newborns with a congenital heart defect. This has been substantiated in the chicken embryo, as congenital heart defects have been induced after homocysteine treatment. Comparable heart defects are observed in venous clipping studies, a model of altered embryonic blood flow. Because of this overlap in heart defects, our aim was to test the hypothesis that homocysteine would cause alterations in embryonic heart function that precede the structural malformations previously described. Therefore, Doppler flow velocity waveforms were recorded in both primitive ventricles and the outflow tract of the embryonic heart of homocysteine treated and control chicken embryos at embryonic day 3.5. Homocysteine treatment consisted of 50 μL 0.05 M L ‐homocysteine thiolactone at 24, 48, and 72 hr. Homocysteine‐treated embryos displayed significantly lower mean heart rates of 134 (SD 22) bpm, compared to 150 (14) bpm in control embryos. Homocysteine treatment caused an inhibiting effect on hemodynamic parameters, and altered heart function was presented by a shift in the proportions of the different wave times in percentage of total cycle time. Homocysteine induces changes in hemodynamic parameters of early embryonic chicken heart function. These changes may precede morphological changes and contribute to the development of CHD defects through alterations in shear stress and shear stress related genes, as seen before in venous clipping studies. Anat Rec,, 2012. © 2012 Wiley Periodicals, Inc.     

Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.