Transversus Abdominis Plane Block for the Diagnosis and Treatment of Chronic Abdominal Wall Pain Following Surgery: A Case Series.

OBJECTIVE: The transversus abdominis plane (TAP) block is a relatively simple regional anesthesia technique which entails the injection of local anesthetics (LA) into the interfascial plane between the internal oblique and transversus abdominis muscles, where nerves supplying the anterolateral abdominal wall course. It is widely used for acute pain management following abdominal surgical procedures. We describe a series of cases in which TAP blocks were used to aid in the diagnosis and treatment of chronic abdominal wall pain (CAWP). DESIGN: Consecutive case series of 5 patients presenting with CAWP. SETTING: Regional referral Center for Pain Medicine of the academic tertiary hospital of Parma, Italy. RESULTS: Five patients received TAP blocks with LA and steroid. Four patients reported ≥50% pain relief within hours of the procedure, and 2 of them maintained low pain intensities at 6- and 12-month follow-up calls. CONCLUSIONS: Transversus abdominis plane blocks are a valuable addition to the diagnostic armamentarium of pain physicians confronted with abdominal pain of unclear origin. Although most patients responded to the LA injection, the varying degrees of response duration may have been influenced by the different etiologies underlying each condition and the variable expressions of placebo responses. Once the abdominal wall and/or its nerves are identified as pain generators, the optimal therapeutic management remains to be determined. Available literature as well as our case series shows that long-term benefit may be obtained with 1 or more injections, but we speculate that this may only be the case for pain with predominantly neuropathic components.

Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery.

OBJECTIVE: The sex of the patients has been shown to affect postoperative pain and morphine consumption; still a clear understanding able to explain the reasons behind this difference struggles to emerge. Our research aimed to investigate one specific aspect of the variability in morphine consumption between sexes. Previous studies have shown that circadian rhythm can influence opioid consumption. Furthermore, circadian rhythm is different between female and male. Our analysis investigated the presence of differences in daily rhythmicity of morphine consumption between males and females. DESIGN: This is a secondary analysis of data collected during 2 years long multicenter clinical trial (NCT01233752). SETTINGS: Clinical data were collected in two Italian hospitals: IRCCS Foundation Policlinico S. Matteo (Pavia) and San Gerardo Hospital (Monza). PATIENTS: The authors recorded data about morphine consumption in 157 patients who underwent major abdominal surgery, who received morphine intravenous patient-controlled analgesia (IV-PCA) as postoperative analgesia. INTERVENTIONS: The authors analyzed the daily periodicity of effective boluses delivered by morphine IV-PCA with Poisson multilevel models, adjusted by the time of start for each pump. An effective bolus was defined as a correctly delivered bolus of 1 mg of morphine. The authors also evaluated the interactions among the time of the day and sex, age (

Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients.

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 <15% stopped the treatment due to side effects (none of which were severe). CONCLUSION: We present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.

A "novel" association to treat pain: tramadol/dexketoprofen. The first drug of a "new pharmacological class".

Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic "ladder" for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and recurrent painful conditions, ranging from nociceptive inflammatory pain to neuropathic pain of moderate/severe intensity. In this review we evaluate the rationale that justifies its use as new class of pharmacological modality to treat pain accordingly also to a more update view of WHO pain ladder.

Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study.

Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05). Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P > 0.05). Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

The serum concentrations of leptin and MCP-1 independently predict low back pain duration.

BACKGROUND: Low back pain (LBP) is a very frequent condition, affecting most people at some point throughout their life. This cross-sectional study was aimed to investigate a selected panel of cytokines and inflammatory biomarkers in patients with or without LBP. METHODS: The study population consisted of 104 patients diagnosed with LBP (52 non-persistent and 52 persistent) and 52 healthy subjects with no LBP. Blood samples were collected for assessment of adiponectin, leptin, monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP). The duration of LBP was categorized as "no pain", "non-persistent LBP" and "persistent LBP". RESULTS: Higher values of CRP and lower concentrations of both leptin and MCP-1 were found in LBP patients compared to controls, whereas adiponectin did not differ among groups. MCP-1 was also lower in patients with non-persistent than in those with persistent LBP. Age, leptin (relative risk, 11.8; 95% CI, 3.9-35.8) and MCP-1 (relative risk, 2.7; 95% CI, 1.7-4.4) were independently associated with presence and duration of LBP. The combination of age, leptin and MCP-1 predicted 61% of the risk of LBP duration. The area under the curve of MCP-1 for distinguishing persistent from non-persistent LBP was 0.65 (95% CI, 0.54-0.76). CONCLUSIONS: Then results of our study suggest that leptin and MCP-1 may be promising biomarkers for diagnosis of acute LBP and its risk to become chronic.

C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection.

The physiology of inflammatory response is modified by the aging process and is substantially affected by multimorbidity and disability. Infection is the most frequent cause of acute inflammation in both adult and older subjects. C-reactive protein (CRP) is the most used biomarker of inflammation, and a substantial amount of literature has demonstrated its importance and clinical usefulness in adult subjects. However, the clinical significance of serum CRP determination has not been completely clarified in older subjects with acute infection, especially in the light of the age-related rearrangements in immunity and cytokine production. Thus, in the present review, we focus on the existing knowledge about serum CRP level interpretation in geriatric patients hospitalized with acute infection. Our aims were to determine the significance of CRP measurement at hospital admission for establishing a diagnosis of infection and/or a prognosis and to evaluate whether it is indicated to repeat hs-CRP measurements during hospital stay for monitoring disease course and, possibly, guiding the discharge timing. We concluded that CRP dosage at hospital admission is helpful to detect acute infection, and particularly sepsis, in geriatric patients, and that CRP elevation may provide valuable short-term prognostic information. At the current state of art, serial CRP measurements are instead not indicated to monitor disease course and plan hospital discharge in this setting.

Past, Present, and Future of Informed Consent in Pain and Genomics Research: Challenges Facing Global Medical Community.

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5-Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally.

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience.

Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.

Perineural catheter infection: a systematic review of the literature.

Perineural catheter infection is a rare but potentially dramatic complication of continuous peripheral nerve block. Different risk factors have been identified and the incidence of infection is increased in trauma victims, intensive care unit patients, immunodeficient individuals, and diabetic patients. Also, postoperative hyperglycemia, the absence of antibiotic prophylaxis, and catheter lasting more than 48 hours seem to be associated with a greater risk of infection. Skin disinfection and a strict aseptic technique during catheter placement are fundamental. The use of micropore filters, antiseptic dressings, catheter tunneling, and aseptic preparation of the infused drug has all been hypothesized to reduce infection rate, but the existing evidence is conflicting. Infection is a rare complication of continuous peripheral nerve blocks. Severe and even fatal cases have been reported, even if morbidity is generally very low. The identification of high risk patients and adoption of preventive measures might reduce the incidence of this complication.

'Omics' biomarkers associated with chronic low back pain: protocol of a retrospective longitudinal study.

INTRODUCTION: Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the '-omics' level (glycomics, Activomics and genome-wide association studies-GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP. METHODS AND ANALYSIS: The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform -omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP. ETHICS AND DISSEMINATION: The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02037789; Pre-results.

Mechanisms of low back pain: a guide for diagnosis and therapy.

Chronic low back pain (CLBP) is a chronic pain syndrome in the lower back region, lasting for at least 3 months. CLBP represents the second leading cause of disability worldwide being a major welfare and economic problem. The prevalence of CLBP in adults has increased more than 100% in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups, with a significant impact on functional capacity and occupational activities. It can also be influenced by psychological factors, such as stress, depression and/or anxiety. Given this complexity, the diagnostic evaluation of patients with CLBP can be very challenging and requires complex clinical decision-making. Answering the question "what is the pain generator" among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can generate therapeutical mistakes. Traditionally, the notion that the etiology of 80% to 90% of LBP cases is unknown has been mistaken perpetuated across decades. In most cases, low back pain can be attributed to specific pain generator, with its own characteristics and with different therapeutical opportunity. Here we discuss about radicular pain, facet Joint pain, sacro-iliac pain, pain related to lumbar stenosis, discogenic pain. Our article aims to offer to the clinicians a simple guidance to identify pain generators in a safer and faster way, relying a correct diagnosis and further therapeutical approach.

Future Perspectives of ERAS: A Narrative Review on the New Applications of an Established Approach.

ERAS approach (Enhanced Recovery After Surgery) is a multimodal, perioperative pathway designed to achieve early recovery after surgery. ERAS has shown documented efficacy in elective surgery, and the concept of "multimodal" and "multidisciplinary" approach seems still to be of higher importance than each single item within ERAS protocols. New perspectives include the use of ERAS in emergency surgery, where efficacy and safety on outcome have been documented, and flexibility of traditional items may add benefits for traditionally high-risk patients. Obstetric surgery, as well, may open wide horizons for future research, since extremely poor data are currently available, and ERAS benefits may translate even on the baby. Finally, the concept of "outcome" may be extended when considering the specific setting of cancer surgery, in which variables like cancer recurrence, early access to adjuvant therapies, and, finally, long-term survival are as important as the reduced perioperative complications. In this perspective, different items within ERAS protocols should be reinterpreted and eventually integrated towards "protective" techniques, to develop cancer-specific ERAS approaches keeping pace with the specific aims of oncologic surgery.

Does a research group increase impact on the scientific community or general public discussion? Alternative metric-based evaluation.

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<0.0001), and publicly viewed (11.1% vs 1.3%, P=0.05) than individual publications. These results support the importance of multidisciplinary research groups in the impact of scientific literature; the interaction and synergy among the research participants allowed the obtainment of high impact-literature in the field of personalized pain medicine. Finally, our findings demonstrate the potential of altmetrics in estimating the value of the research products of a group.

Effect of Preoperative Inflammatory Status and Comorbidities on Pain Resolution and Persistent Postsurgical Pain after Inguinal Hernia Repair.

Poor acute pain control and inflammation are important risk factors for Persistent Postsurgical Pain (PPSP). The aim of the study is to investigate, in the context of a prospective cohort of patients undergoing hernia repair, potential risk factors for PPSP. Data about BMI, anxious-depressive disorders, neutrophil-tolymphocyte ratio (NLR), proinflammatory medical comorbidities were collected. An analysis for correlation between comorbidities and PPSP was performed in those patients experiencing chronic pain at 3 months after surgery. Tramadol resulted less effective in pain at movement in patients with a proinflammatory status. Preoperative hypertension and NLR > 4 were correlated with PPSP intensity. Regional anesthesia was significantly protective on PPSP when associated with ketorolac. Patients with pain at 1 month were significantly more prone to develop PPSP at 3 months. NSAIDs or weak opioids are equally effective on acute pain and on PPSP development after IHR, but Ketorolac has better profile in patients with inflammatory background or undergoing regional anesthesia. Drug choice should be based on their potential side effects, patient's profile (comorbidities, preoperative inflammation, and hypertension), and type of anesthesia. Close monitoring is necessary to early detect pain conditions more prone to progress to a chronic syndrome.

Activity-based costing analysis of the analgesic treatments used in postoperative pain management in Italy.

BACKGROUND: The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique. METHODS: Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway. RESULTS: Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (€ 8.23), whilst the most expensive is continuous peripheral nerve block (€ 223.46). The intravenous patient-controlled analgesia costs € 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (€ 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (€0.58€) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re nata is associated to the lowest cost in terms of health professionals involved (€ 6.25), whilst intravenous PCA is the most expensive one (€ 245.66), requiring a massive monitoring on the part of physicians and nurses. CONCLUSIONS: The analysis successfully collected information about costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in all the nine different Italian hospitals. The interview showed high heterogeneity in the treatment of moderate to severe pain after major abdominal, orthopedic and thoracic surgeries among responding anesthesiologists, with 15 different analgesic modalities reported. The majority of the analgesic techniques considered in the analysis is not recommended by any guideline and their application in real life can be one of the reasons for the high incidence of uncontrolled pain, which is still reported in the postoperative period. Health care costs have become more and more important, although the choice of the best analgesic treatment should be a compromise between efficacy and economic considerations.