La lombalgie aiguë en médecine de premier recours [Acute low back pain in general practice medicine].

The practioner's first concern is knowing how to single out from the immense majority of situations susceptible to a favourable spontaneous evolution those patients with a bad prognostic necessitating reference to a specialist. We present in this paper the clinical steps designed to meet this challenge and a reminder of certain principles of patient diagnosis and care.

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.

A comparison of pain scales in Thai children.

Three commonly used pain scales, the visual analogue scale, the Wong-Baker Faces Pain Scale, and the Faces Pain Scale Revised were administered to 122 Thai children, of whom half were HIV infected, in order to assess their validity. These scales presented moderate to good correlation and moderate agreement, sufficient for valid use in Thai children.

Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in cancer pain and tumor growth in a skin cancer pain model. Injection of luciferase-transfected B16-Fluc melanoma cells into a hindpaw of mouse induced robust tumor growth, as indicated by increase in paw volume and fluorescence intensity. Pain hypersensitivity in this model developed rapidly (<5 days) and reached a peak in 2 weeks, and was characterized by mechanical allodynia and heat hyperalgesia. Tumor growth was associated with JNK activation in tumor mass, dorsal root ganglion (DRG), and spinal cord and a peripheral neuropathy, such as loss of nerve fibers in the hindpaw skin and induction of ATF-3 expression in DRG neurons. Repeated systemic injections of D-JNKI-1 (6 mg/kg, i.p.), a selective and cell-permeable peptide inhibitor of JNK, produced an accumulative inhibition of mechanical allodynia and heat hyperalgesia. A bolus spinal injection of D-JNKI-1 also inhibited mechanical allodynia. Further, JNK inhibition suppressed tumor growth in vivo and melanoma cell proliferation in vitro. In contrast, repeated injections of morphine (5 mg/kg), a commonly used analgesic for terminal cancer, produced analgesic tolerance after 1 day and did not inhibit tumor growth. Our data reveal a marked peripheral neuropathy in this skin cancer model and important roles of the JNK pathway in cancer pain development and tumor growth. JNK inhibitors such as D-JNKI-1 may be used to treat cancer pain.

Les rachialgies inflammatoires [Inflammatory back pain]

Inflammatory back pain is more than just inflammatory pain, but a set of symptoms which presence must evoke a diagnosis of ankylosing spondylitis. However, it is insufficient by itself for a diagnosis which can only be reach as part of a diagnostic strategy searching for other clinical, biological or radiological abnormalities in order to obtain adequate diagnostic probability, while acknowledging the limitations of all these examinations.

Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain

Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.

Interferon-gamma is a critical modulator of CB(2) cannabinoid receptor signaling during neuropathic pain

Nerve injuries often lead to neuropathic pain syndrome. The mechanisms contributing to this syndrome involve local inflammatory responses, activation of glia cells, and changes in the plasticity of neuronal nociceptive pathways. Cannabinoid CB(2) receptors contribute to the local containment of neuropathic pain by modulating glial activation in response to nerve injury. Thus, neuropathic pain spreads in mice lacking CB(2) receptors beyond the site of nerve injury. To further investigate the mechanisms leading to the enhanced manifestation of neuropathic pain, we have established expression profiles of spinal cord tissues from wild-type and CB(2)-deficient mice after nerve injury. An enhanced interferon-gamma (IFN-gamma) response was revealed in the absence of CB(2) signaling. Immunofluorescence stainings demonstrated an IFN-gamma production by astrocytes and neurons ispilateral to the nerve injury in wild-type animals. In contrast, CB(2)-deficient mice showed neuronal and astrocytic IFN-gamma immunoreactivity also in the contralateral region, thus matching the pattern of nociceptive hypersensitivity in these animals. Experiments in BV-2 microglia cells revealed that transcriptional changes induced by IFN-gamma in two key elements for neuropathic pain development, iNOS (inducible nitric oxide synthase) and CCR2, are modulated by CB(2) receptor signaling. The most direct support for a functional involvement of IFN-gamma as a mediator of CB(2) signaling was obtained with a double knock-out mouse strain deficient in CB(2) receptors and IFN-gamma. These animals no longer show the enhanced manifestations of neuropathic pain observed in CB(2) knock-outs. These data clearly demonstrate that the CB(2) receptor-mediated control of neuropathic pain is IFN-gamma dependent.

Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain.

Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It is characterized by the dysregulation of voltage-gated sodium channels (Navs) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying the altered expression of Navs remain unknown. This study investigated the role of the E3 ubiquitin ligase NEDD4-2, which is known to ubiquitylate Navs, in the pathogenesis of neuropathic pain in mice. The spared nerve injury (SNI) model of traumatic nerve injury-induced neuropathic pain was used, and an Nav1.7-specific inhibitor, ProTxII, allowed the isolation of Nav1.7-mediated currents. SNI decreased NEDD4-2 expression in DRG cells and increased the amplitude of Nav1.7 and Nav1.8 currents. The redistribution of Nav1.7 channels toward peripheral axons was also observed. Similar changes were observed in the nociceptive DRG neurons of Nedd4L knockout mice (SNS-Nedd4L-/-). SNS-Nedd4L-/- mice exhibited thermal hypersensitivity and an enhanced second pain phase after formalin injection. Restoration of NEDD4-2 expression in DRG neurons using recombinant adenoassociated virus (rAAV2/6) not only reduced Nav1.7 and Nav1.8 current amplitudes, but also alleviated SNI-induced mechanical allodynia. These findings demonstrate that NEDD4-2 is a potent posttranslational regulator of Navs and that downregulation of NEDD4-2 leads to the hyperexcitability of DRG neurons and contributes to the genesis of pathological pain.

Pain, frailty and comorbidity on older men: the CHAMP study.

Intrusive pain is likely to have a serious impact on older people with limited ability to respond to additional stressors. Frailty is conceptualised as a functional and biological pattern of decline accumulating across multiple physiological systems, resulting in a decreased capacity to respond to additional stressors. We explored the relationship between intrusive pain, frailty and comorbid burden in 1705 community-dwelling men aged 70 or more who participated in the baseline phase of the CHAMP study, a large epidemiological study of healthy ageing based in Sydney, Australia. 9.4% of men in the study were frail (according to the commonly-used Cardiovascular Health Study frailty criteria).Using a combination of self-report and clinical measures, we found an association between frailty and intrusive pain that remained after accounting for demographic characteristics, number of comorbidities, self-reported depressed mood and arthritis (adjusted odds ratio 1.7 (95% confidence interval (CI) 1.1-2.7), p=0.0149). The finding that adjusting for depressed mood, but not a history of arthritis, attenuated the relationship between frailty and intrusive pain points to a key role for central mechanisms. Additionally, men with the highest overall health burden (frail plus high comorbid burden) were most likely to report intrusive pain (adjusted odds ratio 3.0 (95% CI 1.6-5.5), p=0.0004). These findings provide support for the concept that intrusive pain is an important challenge for older men with limited capacity to respond to additional physical stressors. To our knowledge, this is the first study to explore specifically the relationship between pain and frailty.

The INTERMED questionnaire for predicting return to work after a multidisciplinary rehabilitation program for chronic low back pain.

OBJECTIVES: To evaluate the performance of the INTERMED questionnaire score, alone or combined with other criteria, in predicting return to work after a multidisciplinary rehabilitation program in patients with non-specific chronic low back pain. METHODS: The INTERMED questionnaire is a biopsychosocial assessment and clinical classification tool that separates heterogeneous populations into subgroups according to case complexity. We studied 88 patients with chronic low back pain who followed an intensive multidisciplinary rehabilitation program on an outpatient basis. Before the program, we recorded the INTERMED score, radiological abnormalities, subjective pain severity, and sick leave duration. Associations between these variables and return to full-time work within 3 months after the end of the program were evaluated using one-sided Fisher tests and univariate logistic regression followed by multivariate logistic regression. RESULTS: The univariate analysis showed a significant association between the INTERMED score and return to work (P<0.001; odds ratio, 0.90; 95% confidence interval, 0.86-0.96). In the multivariate analysis, prediction was best when the INTERMED score and sick leave duration were used in combination (P=0.03; odds ratio, 0.48; 95% confidence interval, 0.25-0.93). CONCLUSION: The INTERMED questionnaire is useful for evaluating patients with chronic low back pain. It could be used to improve the selection of patients for intensive multidisciplinary programs, thereby improving the quality of care, while reducing healthcare costs.

A pilot study of the efficacy of IL1 blockade by anakinra in acute calcific periarthritis of the rotator cuff

Background/Purpose: Calcific periarthritis of rotator cuff can induce acute and severe shoulder pain and is accompnied by signs of acute inflammation. The calcific deposits are composed of calcium phosphate crystals such as hydroxyapatite or basic calcium phosphate. These crystals stimulate the production and release of IL1b from macrophages, in an analogous manner to MSU and CPPD crystals. As IL1 blockade is effective in reducing signs and symptoms of inflammation in acute gout, we performed a pilot study to study if it is also effective in calcific periarthritis Methods: 5 consecutive patients were included (mean age: 62, 3 females, 2 males) between March 2011 and March 2012. Symptoms of acute shoulder pain at rest had to be present for _7 days before inclusion, associated with limitation of shoulder mobility and the presence on calcification in the rotator cuff by conventional radiography. None of the patients had responded to at least 48 hours of high doses of NSAIDs. Exclusion criteria included no corticosteroid therapy in the last 2 weeks and the exclusion of other rheumatologic or infectious diseases- .Clinical evaluation consisted of patient assessment of pain (total, rest and activity) by VAS (100mm scale) at days 0, 1, 3, 15, 42 and clinical examination of shoulder mobility at days 0, 3, 15. ESR and CRP were measured at days 0, 3. Plain radiographs were performed at days 0 and 15 and an ultrasound examination (including Doppler) was performed at days 0, 3, 15. Anakinra 100mg daily was administered for 3 consecutive days after the first evaluation (day 0). Rescue analgesics were allowed and recorded. Results: At inclusion, all patients had severe shoulder pain: mean (SD) VAS day pain of 72mm (_25mm), mean VAS night pain of 96 (_ 5) and impaired shoulder mobility. CRP was elevated in all of them (mean of 3X). Treatment with anakinra lead to rapid relief of pain in all patients, starting already on the first night following the first injection. The reduction of VAS pain was particularly striking for rest pain: mean (SD) VAS of 4mm (_ 5) at day 1 and this response was maintained for the 5 patients at the end of the three injections without any need of rescue medication. Mean rest VAS was 6 (_8) at day 3. The effect on day pain was less spectacular: mean (SD) VAS at D1 of 30 (_ 18), at D3 of 27 (_ 11). Shoulder mobility also improved and the CRP normalized in 4 of 5 patients at day 3. At day 42, 4 of 5 the patients were still totally asymptomatic. On X rays and US, the calcifications were reduced in size: mean maximal diameter of 21 mm at day 0 to 12 mm at day 15, but did not disappear in any patient. The main change on US was a significant and rapid (at day 3) reduction of Doppler activity around the calcification. Conclusion: This pilot open study suggests that IL-1_ inhibition may be an interesting therapeutic approach in acute calcific periarthritis, especially in patients who have not responded adequately to NSAIDs. The effect on pain seems to be more rapid (within a few hours) than steroid injection although a randomized controlled study needs to be performed to confirm this observation.

La thrombose de varicocèle : une étiologie rare de douleur testiculaire [Varicocele thrombosis: a rare etiology of testicular pain]

Acute testicular pain is frequent in urology. If torsion of the spermatic cord and orchiepididymitis are usual, varicocele thrombosis is an unusual clinical entity we reported.