Immune Competence and Pain: A Narrative Review.

PURPOSE OF REVIEW: This review aims to summarize current knowledge on the pathophysiology of pain and the role of neuro-immune crosstalk in the development of acute and chronic pain (CP). Specifically, the review focuses on the role of immune cells involved in the innate and acquired immune response, emphasizing their bidirectional interactions with the nervous systems and discussing the implications of this crosstalk on acute and CP management. RECENT FINDINGS: In the last two decades, multiple studies have uncovered the important role of the immune system in initiating, maintaining, and resolving pain stimuli. Furthermore, researchers discovered that the immune system interacts tightly with the nervous system, creating a bidirectional crosstalk in which immune cells influence the response of peripheral and central nerve fibers while neurotransmitters and neuropeptides released by nociceptors directly and indirectly modulate the immune response. The neuro-immune crosstalk in acute and CP is a complex and not fully understood process that comprise the interactions of multiple diverse molecules, bidirectional interferences, and numerous redundant processes. Despite the complexity, important steps have been taken in recent years toward explaining the specific roles of each immune cell type and molecule in the initiation, maintenance and resolution of pain. These findings may set the basis for innovative therapeutic options that target the immune system, overcoming the limitations of current treatments in providing pain relief and the disadvantages associated with opioid therapy.

Prevalence of FMS Diagnosis According to ACR 2016 Revised Criteria in a Pain Therapy Centre in Italy: Observational Study.

Background and Objectives: Fibromyalgia syndrome (FMS) is a multifaceted disease with a strong preference for the female sex. It is characterised by chronic widespread pain, sleep-wake disorders, fatigue, cognitive disturbances, and several other somatic symptoms. Materials and Methods: In this prospective observational study, we analysed data regarding 302 patients who were referred to our pain centre for a first clinical assessment evaluation and were then inspected for the physician-based 2016 revision of the ACR diagnostic criteria for FMS, regardless of the final diagnosis previously made by the pain therapist. Results: Among the 280 patients who adhered to the 2016 ACR questionnaire, 20.3% displayed positive criteria for FMS diagnosis. The level of agreement between the FMS discharge diagnosis made by the pain clinician and the ACR 2016 criteria-positivity was moderate (kappa = 0.599, with moderate agreement set at a kappa value of 0.6). Only four patients (1.7%) diagnosed as suffering from FMS at discharge did not satisfy the minimal 2016 ACR diagnostic criteria. Conclusions: This prospective observational study confirmed the diagnostic challenge with FMS, as demonstrated by the moderate grade of agreement between the FMS diagnosis at discharge and the positivity for 2016 ACR criteria. In our opinion, the use of widely accepted diagnostic guidelines should be implemented in clinical scenarios and should become a common language among clinicians who evaluate and treat patients reporting widespread pain and FMS-suggestive symptoms. Further methodologically stronger studies will be necessary to validate our observation.

A hard way to die: when multiple lethal gunshots mean suicide.

Multiple suicidal gunshot wounds are rare and often present a challenging issue for forensic pathologists in determining the manner of death.We describe three cases of suicidal multiple gunshot wounds in which crime scene investigation, cadaveric examination, and autopsy were provided. In all cases, integration of circumstantial data and crime scene investigation suggested a suicidal event.Firstly, we describe the self-infliction of two gunshots to the chest and head in a 90-year-old man by a revolver with wounds to the left lung and lethal wound to both frontal and temporal lobes. The second case concerns a 97-year-old man found dead with two gunshot wounds to the chest by a semi-automatic weapon and bullets penetrated to the left lung and heart. The last case, exceptional in literature, is a 41-year-old man with three self-inflicted gunshots, all-penetrating the left lung and the heart, using a revolver. This paper illustrates that immediate incapacitation can lack even in case of multiple fatal gunshot wounds on instantaneously lethal targets. Therefore, a complete investigation is required for a correct interpretation of the manner of death.An extensive review of literature is also provided.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Obesity as a risk factor for unfavourable outcomes in critically ill patients affected by Covid 19.

BACKGROUND AND AIMS: Recent studies show that obesity is a risk factor for hospital admission and for critical care need in patients with coronavirus disease 2019 (COVID-19). The aim was to determine whether obesity is a risk factor for unfavourable health outcomes in patients affected by COVID-19 admitted to ICU. METHODS AND RESULTS: 95 consecutive patients with COVID-19 (78 males and 18 females) were admitted to ICU and included in the study. Height, weight, BMI, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, CRP, CPK, ICU and hospital length of stay and comorbidities were evaluated. Participants with obesity had a lower 28 day survival rate from ICU admission than normal weight subjects. Cox proportional hazard model-derived estimates, adjusted for age, gender and comorbidity, confirmed the results of the survival analysis (HR:5.30,95%C.I.1.26-22.34). Obese subjects showed longer hospital and ICU stay as compared with normal weight counterpart.Subjects with obesity showed significantly higher CRP and CPK levels than normal weight subjects. CONCLUSION: In individuals with obesity, careful management and prompt intervention in case of suspected SARS-CoV-2 infection is necessary to prevent the progression of the disease towards severe outcomes and the increase of hospital treatment costs.

Epidemiological, pharmacological and sociodemographic characterisation of a population of 386 fibromyalgic patients referred to a tertiary pain centre in Italy.

Fibromyalgia's prevalence in Italy is about 4%. Apart from widespread pain and the three main conditions related to fibromyalgia that are included in its diagnosis (fatigue, unrefreshing sleep and cognitive disorders disturbances), there are a number of minor symptoms that have been associated to fibromyalgia. The current study aimed to characterise fibromyalgic patients referring to a single tertiary pain centre not only for sociodemographic data, but also with special attention on pharmacological history and "minor" symptoms. "Minor" refers to the group of symptoms that were frequently associated and reported with fibromyalgia in various epidemiological studies but are not required for diagnosis. A retrospective analysis was made on 386 patients with confirmed diagnosis based on the 2010 modified criteria. Our results partially confirmed known sociodemographic data, but the prevalence of some "minor" symptoms are impressively high in our population.

Evaluating driving abilities of patients under opioid treatment for chronic pain, by using the Vienna Test System and a newly released APP for smartphones (APP SafeDrive). The old and the new.

OBJECTIVE: The study compare two tests for evaluating the driving abilities of patients undergoing opioid therapy for chronic pain: the Vienna Test System (VTS), a software developed for this purpose, and a new free APP for smartphones (SafeDrive) measuring visual and auditory reaction times. METHODS: One hundred and five patients undergoing long term opioid therapy for chronic pain were enrolled. The driving abilities of study patients were evaluated using two tests, namely the Vienna test System (VTS) and the SafeDrive APP. The concordance between the two tests was evaluated through Cohen's test. In addition we evaluated the correlation between the results of both VTS and SafeDrive tests and prescribed Morphine Equivalent Doses (MEDs), sex, age and the specific drugs taken, by multivariate linear regression analysis. RESULTS: A statistically significant concordance (Cohen's K coefficient=0.476) was found between the SafeDrive APP and the VTS; multivariate linear regression analysis found no significant influences of dosage and type of opioid prescribed on test performances, but significant influences of sex and age. CONCLUSIONS: The Authors found a significant correlation between VTS with SafeDrive test results. The SafeDrive APP is cheaper, easier to use and faster than VTS, and is portable and "usable on the road". Complex behavioral tasks such as driving may be severely impaired by psychoactive drugs, and consequently SafeDrive could be considered a useful portable screening tool to identify drivers with drug associated psychomotor impairment.

Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease.

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD.

Current trends in disability claims due to fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) affects 0.4-8% of the general population predominantly in the female population with a F:M ratio of 3-9:1. It is characterised by persistent widespread pain and other associated clinical conditions such as chronic fatigue, irritable bowel syndrome (IBS), temporomandibular joint dysfunction (TMJD), sleep disorders and cognitive impairment. FMS diagnosis at present is purely clinical because no medical or laboratory examinations are able to identify it with certainty. FMS is not fully recognised worldwide, and patients often do not receive the treatment and disability benefits planned for other chronic diseases even though it gives rise to a very significant social burden due to direct and indirect healthcare costs and the loss of productivity and work. This article describes the medico-legal situation of FMS patients around the world, particularly issues related to the recognition of the disease by health institutions and the provision of disability benefits. We also discuss the current means of assessing disabilities in the medico-legal context, and their possible future improvements.

Suprascapular nerve block for the treatment of hemiplegic shoulder pain in patients with long-term chronic stroke: a pilot study.

Hemiplegic shoulder pain is the most common pain condition after stroke. Suprascapular nerve block is an effective treatment for shoulder pain. The aim of this pilot study was to evaluate the effects of suprascapular nerve block on pain intensity, spasticity, shoulder passive range of motion, and quality of life in long-term chronic stroke patients with hemiplegic shoulder pain. Ten chronic stroke patients (over 2 years from onset) with hemiplegic shoulder pain graded ≥30 mm on the Visual Analogue Scale underwent suprascapular nerve block injection with 1 mL of 40 mg/mL methylprednisolone and 10 mL 0.5% bupivacaine hydrochloride. Main outcome was the Visual Analogue Scale evaluated before and after nerve block at 1 h, 1 week, and 1 month. Secondary outcomes were the modified Ashworth scale and the shoulder elevation, abduction, and external rotation passive range of motion evaluated before the nerve block and after 1 h as well as the American Chronic Pain Association Quality of Life Scale evaluated before and after nerve block at 1 month. The Visual Analogue Scale significantly improved after nerve block at 1 h (P = 0.005) and 1 week (P = 0.011). Significant improvements were found at 1 h after nerve block in the modified Ashworth scale (P = 0.014) and the passive range of motion of shoulder abduction (P = 0.026), flexion (P = 0.007), and external rotation (P = 0.017). The American Chronic Pain Association Quality of Life Scale significantly improved at 1 month after nerve block (P = 0.046). Our findings support the use of suprascapular nerve block for treating hemiplegic shoulder pain in long-term chronic stroke patients.

Assessing and treating primary headaches and cranio-facial pain in patients undergoing rehabilitation for neurological diseases.

BACKGROUND: Pain is a very common condition in patient undergoing rehabilitation for neurological disease; however the presence of primary headaches and other cranio-facial pains, particularly when they are actually or apparently independent from the disability for which patient is undergoing rehabilitation, is often neglected. Diagnostic and therapeutic international and national guidelines, as well as tools for the subjective measure of head pain are available and should also be applied in the neurorehabilitation setting. This calls for searching the presence of head pain, independently from the rehabilitation needs, since pain, either episodic or chronic, interferes with patient performance by affecting physical and emotional status. Pain may also interfere with sleep and therefore hamper recovery. METHODS: In our role of task force of the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN), we have elaborated specific recommendations for diagnosing and treating head pains in patients undergoing rehabilitation for neurological diseases. RESULTS AND CONCLUSION: In this narrative review, we describe the available literature that has been evaluated in order to define the recommendations and outline the needs of epidemiological studies concerning headache and other cranio-facial pain in neurorehabilitation.

Fentanyl Buccal Tablet: A New Breakthrough Pain Medication in Early Management of Severe Vaso-Occlusive Crisis in Sickle Cell Disease.

BACKGROUND: Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder. The principal clinical manifestations of SCD are the chronic hemolytic anemia and the acute vaso-occlusive crisis (VOCs), which are mainly characterized by ischemic/reperfusion tissue injury. Pain is the main symptom of VOCs, and its management is still a challenge for hematologists, requiring a multidisciplinary approach. METHODS: We carried out a crossover study on adult SCD patients, who received two different types of multimodal analgesia during two separate severe VOCs with time interval between VOCs of at least 6 months. The first VOC episode was treated with ketorolac (0.86 mg/kg/day) and tramadol (7.2 mg/kg/day) (TK treatment). In the second VOC episode, fentanyl buccal tablet (FBT; 100 µg) was introduced in a single dose after three hours from the beginning of TK analgesia (TKF treatment). We focused on the first 24 hours of acute pain management. The primary efficacy measure was the time-weighted-sum of pain intensity differences (SPID24). The secondary efficacy measures included the pain intensity difference (PID), the total pain relief (TOTPAR), and the time-wighted sum of anxiety (SAID24). RESULTS: SPID24 was significantly higher in TKF than in TK treatment. All the secondary measures were significantly ameliorated in TKF compared to TK treatment, without major opioid side effects. Patients satisfaction was higher with TKF treatment than with TK one. CONCLUSIONS: We propose that VOCs might require breakthrough pain drug strategy as vaso-occlusive phenomena and enhanced vasoconstriction promoting acute ischemic pain component exacerbate the continuous pain of VOCs. FBT might be a powerful and feasible tool in early management of acute pain during VOCs in emergency departments.

Effect of 5% lidocaine medicated plaster on pain intensity and paroxysms in classical trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain condition affecting one or more branches of the trigeminal nerve. It is characterized by unilateral, sudden, shock-like, and brief painful attacks, which follow the distribution of trigeminal nerve branches, and with no other accompanying sensorimotor or autonomic signs and symptoms. Current guidelines stipulate which therapies represent first-, second-, and third-line treatments for TN, but there is a consistent mismatch between the therapeutic guidelines and the patient's preferences and expectations. CASE SUMMARY: We report on 2 patients with classical TN in whom conventional drugs for TN were not tolerated. In these patients, treatment with 5% lidocaine medicated plaster (LMP) resulted in reduction of pain intensity and the number of pain paroxysms. DISCUSSION: LMP is known to block the sodium channels on peripheral nerves and may cause a selective and partial block of Aδ and C fibers. According to the TN ignition hypothesis, blockage of peripheral afferents by LMP may reduce pain paroxysms. The effect of LMP may outlast the pharmacokinetics of the drug by reducing pain amplification mechanisms in the central nervous system. LMP has limited or no systemic side effects. CONCLUSIONS: LMP may be an effective and well-tolerated treatment option for TN in those patients who do not tolerate or who refuse other therapies. Future randomized controlled studies should better address this issue.

Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis.

Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, p < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.

Anti-CGRP and Anti-CGRP Receptor Monoclonal Antibodies for Migraine Prophylaxis: Retrospective Observational Study on 209 Patients.

BACKGROUND: Migraine is a neurological disorder characterized by attacks of head pain with prevalent unilateral localization, moderate to high intensity and specifically associated accompanying symptoms. METHODS: In this retrospective observational study, we analyzed data regarding 209 patients who had previously been diagnosed with migraine and who were prescribed, between 2019 and 2022, subcutaneous injections of anti-CGRP monoclonal antibodies (mAbs) fremanezumab or galcanezumab or anti-CGRP receptors mAb erenumab regardless of the concomitant assumption of any other acute-phase or prophylactic migraine medication. RESULTS: Regarding efficacy, in the 205 analyzed patients, the change from baseline in terms of MIDAS, HIT-6, MMDs and MAD scores was statistically significant for erenumab and galcanezumab, while for fremanezumab a statistical significance was not achieved likely due to the small sample size. In the treated population, 36 patients (17.5%) reported AEs (pain during injection, transient injection site erythema, nausea, constipation and fatigue). Only 5 patients (2.4%) discontinued the treatment for AEs while 15 patients (7.3%) left for lack of efficacy. CONCLUSIONS: this retrospective study comes out in favor of both significant efficacy and safety of anti-CGRP and anti-CGRP receptors mAbs in migraine patients. Further methodologically stronger studies are necessary to validate our observation.

e-Health Interventions Targeting Pain-Related Psychological Variables in Fibromyalgia: A Systematic Review.

There is growing evidence to support the potential benefit of e-Health interventions targeting psychosocial outcomes and/or pain-related psychological variables for chronic pain conditions, including fibromyalgia syndrome (FMS). This systematic review aims at providing an in-depth description of the available e-Health psychological and/or multicomponent interventions for patients with FMS. Searches were made in PubMed, Cochrane, Web of Science, and PsycINFO up to 15 May 2023, finally including twenty-six articles. The quality of the included articles was medium-high (average quality assessment score of 77.1%). 50% of studies were randomized controlled trials (RCTs) (n = 13), and the majority of them focused exclusively on adult patients with FMS (n = 23) who were predominantly female. Four categories of e-Health modalities were identified: web-based (n = 19), mobile application (m-Health) (n = 3), virtual reality (VR) (n = 2), and video consulting (n = 2). Interventions were mainly based on the cognitive behavioral therapy (CBT) approach (n = 14) and mostly involved contact with a healthcare professional through different digital tools. Overall, a growing number of psychological and multicomponent interventions have been created and delivered using digital tools in the context of FMS, showing their potentiality for improving psychosocial outcomes and pain-related psychological variables. However, some digital tools resulted as underrepresented, and the literature on this topic appears highly heterogeneous precluding robust conclusions.

Epicardial adipose tissue volume and CT-attenuation as prognostic factors for pulmonary embolism and mortality in critically ill patients affected by COVID-19.

BACKGROUND/OBJECTIVES: The aim of this post-hoc analysis was to evaluate if epicardial adipose tissue (EAT) quantity and quality, as evaluated by computed tomography (CT), have a different role in the risk of mortality and pulmonary embolism in critically ill COVID-19 patients admitted to an intensive care unit (ICU). SUBJECTS/METHODS: CT derived EAT volume and density, as well as anthropometric and blood biomarkers, were evaluated in a sample of 138 subjects, 109 men and 29 women, for whom CT images and information on pulmonary embolism were available from a total of 313 subjects who were consecutively admitted to the ICU for COVID-19 from the REINSURE-ARDS prospective registry. RESULTS: A total of 28 patients (20.3%) died during the first 28 days after ICU admission. 26 subjects out of 138 had pulmonary embolism (18.8%). Age, weight, BMI, IL-6 levels and pulmonary embolism prevalence were significantly higher across EAT volume tertiles. Subjects who died in the first 28 days from ICU admission were older, had higher EAT volume, D-dimer, LDH and IL-6 level. After adjustment for age and gender, participants in tertile 3 of EAT volume had lower survival at 28 days from ICU admission as compared to subjects in the tertile 1, HR 2.95 (95% C.I. 1.02-8.49), but after adjusting for potential confounders the relation was no longer significant. No relation between EAT density and mortality was observed. From a binary logistic regression, subjects in tertile 3 of EAT volume and in tertile 1 of EAT density showed a 4 times and 3.6 times increased risk of pulmonary embolism, respectively. CONCLUSIONS: ICU subjects affected by severe COVID-19 with higher EAT volume and low EAT density should be carefully monitored and managed with a prompt and aggressive approach, to prevent serious and life-threatening consequences and the increase of hospital treatment costs.

"INTEGRO INTEGRated Psychotherapeutic InterventiOn" on the Management of Chronic Pain in Patients with Fibromyalgia: The Role of the Therapeutic Relationship.

Fibromyalgia (FM) is a chronic disease characterized by a heterogeneous set of physical and psychological conditions. The chronic experience of disability felt by patients and the impact on quality of life (QoL) of the disease may worsen the cognitive reappraisal ability and contribute to maintaining an altered pain modulation mechanism. This paper presents the study protocol of an INTEGRated psychotherapeutic interventiOn on the management of chronic pain in patients with fibromyalgia (INTEGRO). The aim of the study is to investigate the efficacy of an integrated psychotherapeutic intervention focused on pain management on QoL and pain perception, in a pilot sample of 45 FM patients with idiopathic chronic pain. The contribution of perceived therapeutic relationship (alliance) and physiological attunement, in both the patient and therapist, will be considered as possible mediators of intervention efficacy. Attachment dimensions, traumatic experiences, difficulties in emotion regulation, mindfulness attitude and psychophysiological profile will also be considered as covariates. The objectives are to evaluate longitudinally if patients will experience an increase in QoL perception (primary endpoint), pain-managing self-efficacy and emotion-regulation abilities as well as a reduction in pain intensity (secondary endpoints), considering the mediating role of perceived therapeutic alliance and physiological attunement in both the patient and therapist.

Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN. Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research. Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN. Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.