Pharmacology of pain

This article discusses the mechanisms of action of the main drugs used to treat pain, in particular inflammatory pain. The drugs are described following a classification based on the steps of pain processing that they primarily affect

Enhancement of lysosomal glycohydrolase activity in human primary B lymphocytes during spontaneous apoptosis.

It has been shown that lysosomes are involved in B cell apoptosis but lysosomal glycohydrolases have never been investigated during this event. In this study we determined the enzymatic activities of some lysosomal glycohydrolases in human tonsil B lymphocytes (TBL) undergoing in vitro spontaneous apoptosis. Fluorimetric methods were used to evaluate the activities of β-hexosaminidases, α-mannosidase, β-mannosidase, β-galactosidase, β-glucuronidase and α-fucosidase. Results show that in TBL during spontaneous apoptosis, there is a significant increase in the activity of β-hexosaminidases, α-mannosidase, β-mannosidase and β-galactosidase. Also β-glucuronidase and α-fucosidase activities increase but not in a significant manner. Further studies on β-hexosaminidases revealed that also mRNA expression of the α- and β-subunits, which constitute these enzymes, increases during spontaneous TBL apoptosis. When TBL are protected from apoptosis by the thiol molecule N-acetyl-L-cysteine (NAC), there is no longer any increase in glycohydrolase activities and mRNA expression of β-hexosaminidase α- and β-subunits. This study demonstrates for the first time that the activities and expression of some lysosomal glycohydrolases are enhanced in TBL during spontaneous apoptosis and that these increases are prevented when TBL apoptosis is inhibited

evaluation of the peak bone mass by quantitative heel ultrasound in young women of the centre of italy

Objective: To measure the reference young adult mean values in healthy women of the centre of Italy by Quantitative heel UltraSound (QUS). Methods: The study group was composed by 70 caucasian women: mean age was 25.4 years (Standard Deviation 4.7), mean weight was 58 Kg (SD 8.2), mean height was 166 cm (SD 5.8), mean BMI was 20.9 kg/m2 (SD 2.5). Every subject was evaluated firstly with an original questionnaire to discover risk factors (like for example steroids consumption, recent fractures of the lower limb), then was measured by quantitative heel ultrasonometry Hologic Sahara. Results: Mean extimated Bone Mineral Density (BMD) 0.588 g/cm2 (SD 0.124) mean Quantitative Ultrasound Index (QUI) 105.0 (SD 19.6), mean Speed of Sound (SOS) 1564.2 m/s (SD 31.4), mean Broadband Ultrasound Attenuation (BUA) 84.8 dB/MHz (SD 17.4). No significant correlation was found between QUS parameters and anthropometric data. A correlation was found between every QUS parameters. No significant differences were found about QUI and extimated BMD, between our results and Hologic normative data for European women. Conclusions: It is very important to develop specific reference values for any measurement device and site of skeleton especially in the age of reaching the peak bone mass because the T score is then measured referring to these data. Usually the normative data are supplied by manufacturer and are based on large multicentric study. In our opinion it could be helpful to verify if these data are compatible with the population examined in every region

Primary Sjögren syndrome‐related peripheral neuropathy: a systematic review and meta‐analysis

Background and purpose Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. Methods A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. Results The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%–20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies—particularly trigeminal—are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. Conclusions PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration

Systematic review of randomized controlled trials in the treatment of dry eye disease in Sjogren syndrome

Primary Sjögren’s syndrome is an autoimmune disease characterized by dry eye and dry mouth. We systematically reviewed all the randomized controlled clinical trials published in the last 15 years that included ocular outcomes. We found 22 trials involving 9 topical, 10 oral, 2 intravenous and 1 subcutaneous modalities of treatment. Fluoromethalone eye drops over 8 weeks were more effective than topical cyclosporine in the treatment of dry eye symptoms and signs; similarly, indomethacin eye drops over 1 month were more efficacious than diclofenac eye drops. Oral pilocarpine 5 mg twice daily over 3 months was superior to use of lubricants or punctal plugs for treating dry eye, but 5% of participants had gastrointestinal adverse effects from pilocarpine, though none discontinued treatment. In contrast, etanercept, a TNF-alpha blocking antibody, administered as subcutaneous injections twice weekly, did not improve dry eye significantly compared to placebo injections. In conclusion, topical corticosteroids have been shown to be effective in dry eye associated with Sjögren’s syndrome. As some topical non-steroidal anti-inflammatory drugs may be more effective than others, these should be further evaluated. Systemic secretagogues like pilocarpine have a role in Sjögren’s syndrome but the adverse effects may limit their clinical use. It is disappointing that systemic cytokine therapy did not produce encouraging ocular outcomes but participants should have assessment of cytokine levels in such trials, as those with higher baseline cytokine levels may respond better.published_or_final_versio

Where should analgesia lead to? Quality of life and functional recovery with tapentadol

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, tapentado

Tapentadol in the treatment of osteoarthritis: pharmacological rationale and clinical evidence

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, tapentado