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Chronic pain is an important health and social problem. Misuse and abuse of opioids in chronic non-cancer pain management seem to be a huge problem, in some countries. This could probably affect the normal use of such analgesics in patients in need of them. Basic and clinical researches should find the solution to mitigate the potential damage. Dysregulation of mast cell and microglia activation plays an important role in the pathogenesis and management of chronic pain. Persistent mast cell activation sensitizes nociceptors and initiates central nervous system inflammatory processes, involving microglial cell activation and sensitization of spinal somatosensory neurons. Exposure of mast cells and microglia to opioids is well known to provoke activation of these non-neuronal immune cell populations, thereby contributing to an exacerbation of pro-inflammatory and pro-nociceptive processes and promoting, over the long-term, opioid-induced hyperalgesia and tolerance. This review is intended to provide the reader with an overview of the role for these non-neuronal cells in opioid-induced chronic pain and tolerance as a consequence of prolonged exposure to these drugs. In addition, we will examine a potential strategy with the aim to modulate opioid-induced over-activation of glia and mast cells, based on endogenous defense mechanisms and fatty acid amide signaling molecules. 7 1 59 75

Lorenzo Panella,1 Giuseppe Rinonapoli,2 Stefano Coaccioli31Rehabilitation Department, ASST Pini-CTO, 20100 Milan, Italy; 2Dipartimento di Scienze Chirurgiche, s.c. Ortopedia e Traumatologia Università di Perugia. Ospedale S.Maria della Misericordia, 06100 Perugia, Italy; 3Department of Medicine, Sezione di Clinica Medica e Anatomia Patologia, 05100 Terni, ItalyAbstract: Chronic pain is a major health-care problem worldwide, affecting more than one out of five adults in Europe. Although multiple analgesic agents have been extensively investigated in terms of clinical response and tolerability profile, few studies have focused on the impact of these therapies on patients’ quality of life (QoL). Of note, improvement in QoL, together with functional recovery, has been recognized since the late 1990s as two main goals of analgesic therapy. Tapentadol is a novel analgesic molecule that synergistically combines two mechanisms of action, μ-opioid receptor agonism and norepinephrine reuptake inhibition, and for which multiple literature data are available that confirm its efficacy and safety in controlling pain. This narrative review summarizes the information available on the impact of tapentadol on QoL, with the aim to provide clinicians with a comprehensive overview of the analgesic effects of tapentadol prolonged release beyond the reduction of pain.Keywords: pain, quality of life, tapentadol

Giuseppe Rinonapoli,1 Stefano Coaccioli,2 Lorenzo Panella31Dipartimento di Scienze Chirurgiche, s.c. Ortopedia e Traumatologia Università di Perugia, Ospedale S. Maria della Misericordia, 06100 Perugia, Italy; 2Department of Medicine, Sezione di Clinica Medica e Anatomia Patologia, Terni, Italy; 3Rehabilitation Department, ASST Pini-CTO, Milan, ItalyAbstract: Osteoarthritis (OA) is the most prevalent joint disease in older people worldwide. Pain owing to OA is considered one of the most frequent causes of chronic pain; however, current pharmacological approaches have some limitations in terms of efficacy and safety. Of note, descending inhibitory pain pathways are often disrupted in chronic OA pain, and pharmacotherapies targeting those pathways – eg, those that block norepinephrine reuptake may be more appropriate for managing chronic pain than pure μ-opioid receptor (MOR) agonists. Tapentadol is an analgesic molecule, which combines two synergistic mechanisms of action, MOR, and norepinephrine reuptake inhibition. This narrative review will briefly discuss the mechanisms contributing to the onset and maintenance of pain in OA patients; clinical data on the use of tapentadol in this setting will then be presented and commented.Keywords: osteoarthritis, pain, tapentadol

Giuseppe Rinonapoli,1 Stefano Coaccioli,2 Lorenzo Panella31Dipartimento di Scienze Chirurgiche, s.c. Ortopedia e Traumatologia Università di Perugia, Ospedale S. Maria della Misericordia, 06100 Perugia, Italy; 2Department of Medicine, Sezione di Clinica Medica e Anatomia Patologia, Terni, Italy; 3Rehabilitation Department, ASST Pini-CTO, Milan, ItalyAbstract: Osteoarthritis (OA) is the most prevalent joint disease in older people worldwide. Pain owing to OA is considered one of the most frequent causes of chronic pain; however, current pharmacological approaches have some limitations in terms of efficacy and safety. Of note, descending inhibitory pain pathways are often disrupted in chronic OA pain, and pharmacotherapies targeting those pathways – eg, those that block norepinephrine reuptake may be more appropriate for managing chronic pain than pure μ-opioid receptor (MOR) agonists. Tapentadol is an analgesic molecule, which combines two synergistic mechanisms of action, MOR, and norepinephrine reuptake inhibition. This narrative review will briefly discuss the mechanisms contributing to the onset and maintenance of pain in OA patients; clinical data on the use of tapentadol in this setting will then be presented and commented.Keywords: osteoarthritis, pain, tapentadol

There is a wide evidence that Psoriatic Arthritis (PsA) as well as Psoriasis (Ps) lead to significant health problems and interfere with the patient quality of life (QoL). Even though a validated questionnaire for Ps is available, no questionnaire for PsA is currently present in literature. The aim of our work has been to confirm the efficacy of our original questionnaire as well as to validate it, through the comparison with other existing recognised and accepted questionnaires, such as MOF-SF36, HAQ, McGill Pain Questionnaire, and Zeung Self-Rating Depression and Anxiety Scales.We have realized a questionnaire for PsA (Psoriatic Arthritis Impact Questionnaire, PAIP), in terms of psychological and rheumatological evaluation, QoL, social and economic assets.The statistical comparisons between PAIP and the accepted questionnaires (see above) confirm that PAIP is widely validated and represents a useful tool suitable for clinical evaluation and management of patients with PsA.The indexes of the correlation among the different parts of PAIP and the other questionnaires have shown positive correlations. Moreover, PAIP presents a dedicated unit for the economical and therapeutic parameters, The short time for compilation (15 minutes), the easy of comprehension of the questions, and - above all - the validation of PAIP, make our questionnaire a useful tool, suitable for the clinical management of the patients with PsA.

Diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30–35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to “tailor” more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young.

Ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), possesses analgesic, antipyretic and anti-inflammatory properties. Oral KP is widely used in musculoskeletal pain and inflammation in muscles and joints, including arthritis pain, osteoarthritis, stiffness of the joints, soft tissue rheumatism, and sports injuries. In common with all NSAIDs, oral KP has been associated with systemic adverse events and in particular gastrointestinal disorders. Topical application of the active ingredient is locally effective and at the same time minimises the risk of systemic adverse events. Pharmacokinetic studies show that serum levels of the active ingredient following topical KP 2.5% gel are less than 1% of those reported after oral dosing, thereby providing good levels of pain relief without the systemic adverse events normally associated with oral NSAIDs. In comparative studies, topical KP 2.5% gel twice daily showed clinical benefits in patients with a range of musculoskeletal conditions. KP 2.5% gel is generally well tolerated but the treated skin area should not be exposed to direct sunlight, including solarium (sunbeds), during the treatment and for 2 weeks afterwards as topical photosensitization has been reported. To our knowledge, this is the first overview on the use of topical KP (tKP) 2.5% gel which includes data from both clinical trials and from 'real-life' clinical practice.

Bone Metabolism and HIV Infection

The systemic vasculitis are characterised by an inflammatory process of the blood vessel walls. These may affect any of the vessels and organs, resulting in a diverse range of signs and symptoms. These polymorphic clinical manifestations, combined with the non-specific aetiology of the histological lesions, render the diagnosis for any single form of vasculitis more complicated. The problem lies in the various forms of vasculitis with analogous clinical presentations, requiring very different prognosis and treatment. This review has been realised in order to examine the modern approach to achieve and to maintain the clinical remission and to treat the relapse.

In 1999, the Italian Society of Rheumatology started a project to determine the prevalence and clinical characteristics of aggressive rheumatoid arthritis (ARA).For 1 year, all patients with RA for5 years and referred to participating centers were entered in a registry and classified as having ARA if they fulfilled the following criteria: 10 swollen joints for at least 6 weeks, positive rheumatoid factor (RF), and at least one bone erosion (if disease duration of 2 years); (a) RF-positive and having 10 swollen joints or at least one newly eroded joint, or (b) if RF-negative, having 10 swollen joints and at least one newly eroded joint (if disease duration2 to5 years).The 94 participating centers enrolled 1218 patients with RA, 1130 of whom had enough data to be classified as ARA (29.0%) or non-ARA (71.0%). The frequency of ARA was 15% in the 2-year group and 63% in the2 to5-year group, but 35% of the patients in the 2-year group had erosions. Bone erosions were associated with disease duration, a Health Assessment Questionnaire value1.5, female sex, and RF positivity. Conditions other than RA were recorded in about 50% of the patients, and only 30% 40% were taking disease modifying antirheumatic drugs.In an Italian RA population, the GIARA (Gruppo Italiano Artrite Reumatoide Aggressiva) criteria for ARA were met by 15% of the patients with disease duration of 2 years, but erosions were seen in 35%. Upon referral, most of the RA patients were inadequately treated and had other conditions.

Study background: The aim of this study was the investigation the role of meditation in a cohort of Italy resident subjects coming from Thailand, following only complementary medicine. Methods: The cohort of subjects has been examined (60 subjects) by the visual analogue scale (VAS) scale for pain measurement. The subjects have been divided in two groups: experts (>10 years) and Lower experts in meditation (