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Guido Fanelli,1,2 Giuliano De Carolis,3 Claudio Leonardi,4 Adele Longobardi,5,6 Ennio Sarli,7,8 Massimo Allegri,1,2 Michael E Schatman9 1Anesthesia, Critical Care and Pain Medicine Unit, Division of Surgical Sciences, Department of Medicine and Surgery, University of Parma, 2Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliero Universitaria Parma, Parma, 3Pain Therapy Service, Azienda Ospedaliero Universitaria Pisana, Pisa, 4Department of Drug Addiction Diseases, Local Public Health of Rome, Rome, 5Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, 6Young Against the Pain (YAP) Group, Parma, 7Progetti Live Surgery, 8PinHub Group, Florence, Italy; 9Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Background: Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use.Methods: This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment.Results: As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and

Manuela De Gregori,1-3,* Valeria Scotti,4,* Annalisa De Silvestri,4 Moreno Curti,4 Guido Fanelli,2,5,6 Massimo Allegri,2,5,6 Michael E Schatman,2,7 1Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2Study In Multidisciplinary PAin Research Group, Parma, Italy; 3Young Against Pain Group, Parma, Italy; 4Center for Scientific Documentation and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 5Anesthesia, Critical Care, and Pain Medicine, Department of Surgical Sciences, University of Parma, Italy; 6Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliero, Universitaria di Parma, Parma, Italy; 7US Pain Foundation, Bellevue, WA, USA *These authors contributed equally to this work. Abstract: In this study, we investigated the impact of scientific publications of the Italian SIMPAR (Study In Multidisciplinary PAin Research) group by using altmetrics, defined as nontraditional metrics constituting an alternative to more traditional citation-impact metrics, such as impact factor and H-index. By correlating traditional and alternative metrics, we attempted to verify whether publications by the SIMPAR group collectively had more impact than those performed by its individual members, either in solo publications or in publications coauthored by non-SIMPAR group investigators (which for the purpose of this study we will refer to as “individual publications”). For all the 12 members of the group analyzed (pain therapists, biologists, and pharmacologists), we created Open Researcher and Contributor ID and Impact Story accounts, and synchronized these data. Manually, we calculated the level metrics for each article by dividing the data obtained from the research community by those obtained from the public community. We analyzed 759 articles, 18 of which were published by the SIMPAR group. Altmetrics demonstrated that SIMPAR group publications were more likely to be saved (77.8% vs 45.9%), discussed (61.1% vs 1.1%, P

Guido Fanelli,1 Andrea Fanelli2 1Anesthesia and Intensive Care Unit, University of Parma, Parma, 2Anesthesia and Intensive Care Unit, Policlinico S Orsola-Malpighi, Bologna, Italy Abstract: Chronic pain is a highly disabling condition, which can significantly reduce patients’ quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC) occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC. Keywords: chronic pain, opioid-induced constipation, opioids, oxycodone–naloxone

Roberto Casale,1,2 Maria Di Matteo,3,7 Cristina E Minella,4,7 Guido Fanelli,5,7 Massimo Allegri4,6,71Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation Salvatore Maugeri, IRCCS, Pavia, 2EFIC Montescano School, Montescano, 3Anesthesia and Intensive Care I, 4Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 5Department of Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 6Department of Clinical, Surgical, Diagnostic and Pediatric Science, University of Pavia, Pavia, 7Study In Multidisciplinary Pain Research Group, Parma, ItalyAbstract: Post-herpetic neuralgia (PHN) is neuropathic pain persisting after an acute episode of herpes zoster, and is associated with severe pain and sensory abnormalities that adversely affect the patient's quality of life and increase health care costs. Up to 83% of patients with PHN describe localized neuropathic pain, defined as “a type of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain”. Topical treatments have been suggested as a first-line treatment for localized neuropathic pain. Use of 5% lidocaine medicated plaster could reduce abnormal nervous peripheral discharge and via the plaster could have a “protective” function in the affected area. It has been suggested that use of this plaster could reduce pain as well as the size of the painful area. To evaluate this possible outcome, we retrospectively reviewed eight patients with PHN, treated using 5% lidocaine medicated plaster. During a follow-up period of 3 months, we observed good pain relief, which was associated with a 46% reduction in size of the painful area after one month (from 236.38±140.34 cm2 to 128.80±95.7 cm2) and a 66% reduction after 3 months (81.38±59.19 cm2). Our study cohort was composed mainly of elderly patients taking multiple drugs to treat comorbidities, who have a high risk of drug–drug interactions. Such patients benefit greatly from topical treatment of PHN. Our observations confirm the effectiveness of lidocaine plasters in the treatment of PHN, indicating that 5% lidocaine medicated plaster could reduce the size of the painful area. This last observation has to be confirmed and the mechanisms clarified in appropriate larger randomized controlled trials.Keywords: localized neuropathic pain, topical treatment, chronic pain, drug–drug interactions, patient's outcome

The first results of a study of monitoring species and habitats in the framework of the Life 04NAT/IT/000190 "Tutela dei siti Natura 2000 gestiti dal Corpo Forestale dello Stato" are presented. This study was carried out by the Department of Plant Biology of the University of Rome (La Sapienza) and the National Forest Service. We focused the investigation on the relationships between herbaceous species and pedological parameters (humus and soil) in Central-Apennine beech forests. Data have been collected through 40 phytosociological relevés, 15 soil profiles and 40 humus profiles in 40 forest plots, between March 2005 and September 2006. In this paper we presented data elaborated on a subset of 15 plots where soil profiles were available. The species of undergrowth showed different ecological requirements to some edaphic and humus parameters (pH, sand, loam, clay, organic matter, nitrogen, carbon/nitrogen ratio, Ca++, K+;thickness and carbon content of the organic layers): significant correlations have been found using Pearson correlation test. The multiple regression analysis allowed to identify the factors more influencing the species distribution: thickness of the organic layers, carbon content (% C) and carbon/nitrogen ratio (C/N). Basing on the thickness of humus horizons (OL, OF, OH), and on carbon content, two species groups with different ecology have been recognized: (a) nemoral species typical of shady beech stands on oligomull/dysmull/thin amphimull (0 < 1cm.; 5.7 < %C < 9.9); (b) heliophilous species of more xeric stands on thick amphimull (1.25 < 11.5 cm.; 9.9 < %C < 13.7). The relationships among species and soil parameters and humus forms allow to recognize small differences within a homogeneous habitat and therefore they can provide management indications also at micro-scale level.