Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.

Consensus interdisciplinaire CHUV-HUG sur la prise en charge des douleurs du dos. Son application lausannoise dans la filière du dos [Inter-hospital CHUV-HUG medical consensus of back pain management. Its application in care pathways within CHUV of Lausanne].

Back pain is a considerable economical burden in industrialised countries. Its management varies widely across countries, including Switzerland. Thus, the University Hospital and University of Lausanne (CHUV) recently improved intern processes of back pain care. In an already existing collaborative context, the two university hospitals in French-speaking Switzerland (CHUV, University Hospital of Geneva), felt the need of a medical consensus, based on a common concept. This inter-hospital consensus produced three decisional algorithms that bear on recent concepts of back pain found in literature. Eventually, a fast track was created at CHUV, to which extern physicians will have an organised and rapid access. This fast track aims to reduce chronic back pain conditions and provides specialised education for general practitioners-in-training.

Nedd4-2 ubiquitin ligase: a contributor to experimental neuropathic pain?

Background: Neuropathic pain is associated with altered expression of voltage-gated sodium channels (VGSCs) leading to peripheral nerve hyperexcitability. Interestingly, in cell expression systems, the ubiquitin ligase Nedd4-2 regulates the cell membrane density of the most abundant peripheral and pain-related VGSC, namely Nav1.7, and decreases its sodium current. Yet nothing is known about the involvement of Nedd4-2 in nociception and chronic pain. Therefore, the goal of this study is (i) to characterize Nedd4-2 and Nav1.7 expression in an experimental model of neuropathic pain (ii) to design by viral vector-mediated gene therapy an approach to depict the implication of Nedd4-2 in chronic pain. Methods: Western Blot and immunohistochemistry experiments detecting Nav1.7 and Nedd4-2 were performed in rodent DRGs 7 days after spared nerve injury (SNI). For the viral vector-mediated gene therapy, a recombinant Adeno-Associated Virus (rAAV2/6) was generated expressing the Nedd4-2 gene. Intrathecal injection of rAAV2/6 was followed 2 weeks after by the SNI surgery. Data are expressed in mean ± SEM, n = 4 in each condition. Results: Immunofluorescence on DRGs neurons reveals a decreased number of positive Nedd4-2 cells in the SNI model (27.0 ± 1.2%) versus sham group (43.4 ± 3.5%; p <0.005), as well as an increase in positive Nav1.7 cells in SNI (50.1 ± 2.9%) versus Sham (41.6 ± 1.8%; p <0.05). The change of Nedd4-2 expression was confirmed by western-blot analysis. In addition, we show that Nedd4-2 and Nav1.7 are largely expressed in overlapping cell populations, chiefly colocalizing with markers of small nociceptive neurons. Furthermore, we report that intrathecal injection of rAAV is able to counteract the reduction of Nedd4-2 expression in SNI animals. Conclusion: Our results indicate that Nedd4-2 is mainly expressed in nociceptors and downregulated after nerve injury. Moreover, our data suggest that the reduction of Nedd4-2, after nerve injury, may modulate Nav1.7 activity and contribute to hyperexcitability in neuropathic pain. A normal level of Nedd4-2 can be restored using a viral vector and we will further assess its functional effect on pain sensitivity.

Douteur testiculaire, un défi diagnostique [Testicular pain, a diagnostic challenge?].

Scrotal pain is frequently encountered in practice, as it affects 4 men in 1000, with a peak of incidence between the ages of 45 and 50. After excluding an urological or gastrointestinal cause, referred pain of musculoskeletal origin should be considered, even in the absence of back pain. Described by Dr. Robert Maigne, this referred pain originates from a minor intervertebral dysfunction of the thoracolumbar junction. Imaging of the spine is not helpful. Rather, the diagnosis is made by seeking pain triggered by the mobilization of the lumbar vertebrae; the pinch and roll skin manoeuvre will highlight this referred pain. Treatment is symptomatic, though manual therapies by spine specialists are also recommended.

Fatal tolperisone poisoning: Autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm(®)) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0mg/l, 14mg/l and 19mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.

Disc degeneration: current surgical options.

Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

Evaluation des technologies médicales : travaux présentés pendant le Congrès TEKMED 87 = Assessment of medical technologies : the papers presented during the TEKMED 87 Congress

[Table des matières] Technology assessment in health care in the United States: an historical review / S. Perry. - The aims and methods of technology assessment / JH Glasser. - Evaluation des technologies de la santé / A. Griffiths. - Les données nécessaires pour l'évaluation des technologies médicales / R. Chrzanowski, F. Gutzwiller, F. Paccaud. - Economic issues in technology assessment/DR Lairson, JM Swint. - Two decades of experience in technology assessment: evaluating the safety, performance, and cost effectiveness of medical equipment / JJ Nobel. - Demography and technology assessment / H. Hansluwka. - Méthodes expérimentale et non expérimentale pour l'évaluation des innovations technologiques / R. Chrzanowski, F. Paccaud. - Skull radiography in head trauma: a successful case of technology assessment / NT Racoveanu. - Complications associées à l'anesthésie: une étude prospective en France / L. Tiret et al. - Impact de l'information publique sur les taux opératoires: le cas de l'hystérectomie / G. Domenighetti, P. Luraschi, A. Casabianca. - The clinical effectiveness of acupuncture for the relief of chronic pain / MS Patel, F. Gutzwiller, F. Paccaud, A. Marazzi. - Soins à domicile et hébergement à long terme: à la recherche d'un développement optimum / G. Tinturier. - Economic evaluation of six scenarios for the treatment of stones in the kidney and ureter by surgery or ESWL / MS Patel et al. - Technology assessment and medical practice / F. Gutzwiller. - Technology assessment and health policy / SJ Reiser. - Global programme on appropriate technology for health, its role and place within WHO / K. Staehr Johansen.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Care related pain in rehabilitation after orthopedic trauma: An exploratory study with qualitative data.

OBJECTIVE: Care related pain (CRP) is generally under-estimated and rarely studied in rehabilitation as well as in general medecine. Beliefs about pain influence psychological distress, adjustment to pain and physical disability. In this sense, perceptions of CRP could limit recovery. This exploratory study aims to understand patients' and caregivers' subjective perceptions and beliefs about CRP. PATIENTS AND METHODS: Questionnaires about CRP were submitted to members of the interdisciplinary team of a rehabilitation hospital and to patients with musculoskeletal complaints (cross-sectional design). Twenty patients were also individually interviewed (qualitative data). Four topics were addressed: frequency of CRP, situations and procedures causing CRP, beliefs about CRP and means used to deal with CRP. RESULTS: Seventy-five caregivers and 50 patients replied to the questionnaire. CRP is a very common experience in rehabilitation and it is recognized by both groups. Generally, the situations causing CRP reflect the specificity of rehabilitation (mobilization...) and are similarly perceived by patients and caregivers, with patients considering them as more painful. Beliefs about CRP are clearly different from those usually associated with pain. Both groups point out the utilitarian and the inevitable character of CRP. They differ on that, that patients had a more positive view about CRP. They associate it more often with progress and see it as acceptable at least until a certain limit. They are also able to perceive the richness of means used by physiotherapists to help them coping with CRP. CONCLUSION: Our data may suggest new keys to motivate patient to be active in rehabilitation for example in choosing carefully arguments or words which may fit theirs' beliefs about CRP, or in using various means to manage CRP. Promoting the use of relational competences with chronic pain patients and of a patient-centred approach may also be a concern in training caregivers.

Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusion

La hipnosis en el tratamiento del dolor crónico

For a long time, hypnosis has been associated with knowledge areas of little apparent scientific validity. Fourtanely, in recent years, hypnosis has proved to be a useful technique for intervention in the health area. The area where mor estudies have been conducted and with greater success is on treatment of chronic pain. However, some obstacles must yet be overcome: the limited use of hypnosis in the public health services in Spain, and the resources assigned by universities for researchand professional trainingon these techniques are scarce. This paper aims to briefly review the current state of hypnosis in the treatment of chronic pain, and advocates for its integration within a multidisciplinary treatment of chronic pain.

Differential effects of two virtual reality interventions: distraction versus pain control

There is evidence that virtual reality (VR) pain distraction is effective at improving pain-related outcomes. However, more research is needed to investigate VR environments with other pain-related goals. The main aim of this study was to compare the differential effects of two VR environments on a set of pain-related and cognitive variables during a cold pressor experiment. One of these environments aimed to distract attention away from pain (VRD), whereas the other was designed to enhance pain control (VRC). Participants were 77 psychology students, who were randomly assigned to one of the following three conditions during the cold pressor experiment: (a) VRD, (b) VRC, or (c) Non-VR (control condition). Data were collected regarding both pain-related variables (intensity, tolerance, threshold, time perception, and pain sensitivity range) and cognitive variables (self-efficacy and catastrophizing). Results showed that in comparison with the control condition, the VRC intervention significantly increased pain tolerance, the pain sensitivity range, and the degree of time underestimation. It also increased self-efficacy in tolerating pain and led to a reduction in reported helplessness. The VRD intervention significantly increased the pain threshold and pain tolerance in comparison with the control condition, but it did not affect any of the cognitive variables. Overall, the intervention designed to enhance control seems to have a greater effect on the cognitive variables assessed. Although these results need to be replicated in further studies, the findings suggest that the VRC intervention has considerable potential in terms of increasing self-efficacy and modifying the negative thoughts that commonly accompany pain problems.

The association between obesity and back pain in nine countries: a cross-sectional study

BACKGROUND: The association between obesity and back pain has mainly been studied in high-income settings with inconclusive results, and data from older populations and developing countries are scarce. The aim of this study was to assess this association in nine countries in Asia, Africa, Europe, and Latin America among older adults using nationally-representative data. METHODS: Data on 42116 individuals ≥50 years who participated in the Collaborative Research on Ageing in Europe (COURAGE) study conducted in Finland, Poland, and Spain in 2011-2012, and the World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010 were analysed. Information on measured height and weight available in the two datasets was used to calculate Body Mass Index (BMI). Self-reported back pain occurring in the past 30 days was the outcome. Multivariable logistic regression analysis was used to assess the association between BMI and back pain. RESULTS: The prevalence of back pain ranged from 21.5% (China) to 57.5% (Poland). In the multivariable analysis, compared to BMI 18.5-24.9 kg/m(2), significantly higher odds for back pain were observed for BMI ≥35 kg/m(2) in Finland (OR 3.33), Russia (OR 2.20), Poland (OR 2.03), Spain (OR 1.56), and South Africa (OR 1.48); BMI 30.0-34.0 kg/m(2) in Russia (OR 2.76), South Africa (OR 1.51), and Poland (OR 1.47); and BMI 25.0-29.9 kg/m(2) in Russia (OR 1.51) and Poland (OR 1.40). No significant associations were found in the other countries. CONCLUSIONS: The strength of the association between obesity and back pain may vary by country. Future studies are needed to determine the factors contributing to differences in the associations observed.

O uso da prótese na correção das hérnias da parede abdominal é um avanço, mas o seu uso indiscriminado, um abuso

The objective is to alert the surgeon about the indiscriminate use of synthetic prosthesis in the correction of inguinal and incisional hernias. The authors provide a brief history of surgery on hernias and a review of the literature, showing the importance of classifying inguinal hernias to fit the type of surgical correction with the defect found, abstaining from treating all hernias, with the same type of surgical procedure. In our opinion, small indirect inguinal hernias (type 1 and 2 of Gilbert) and hernias in women must not, in general, be treated with prostheses. The synthetic material should be reserved for direct and large indirect hernias. Even so, this attitude, besides determining a higher cost for the procedure, can lead to important complications such as infection, rejection, fistula formation, chronic pain, alterations in spermatogenesis and the possibility of carcinogenesis, according to more recent reports. The physiology and anatomy of the abdominal wall should be considered when dealing with incisional hernia corrections, where the surgeon can choose among many techniques to correct those defects, and in selected cases, utilize synthetic material. We conclude that although the use of biomaterials has constituted a great advance in surgery for abdominal wall hernia corrections because they decrease recurrences, and permit treatment of large abdominal hernias, the indiscriminate prosthesis usage is an abuse, and it can determine many serious complications, certainly avoidable with a well indicated non mesh technique .