High Prevalence of Pain Sensitization in Knee Osteoarthritis: A Meta-Analysis with Meta-Regression

Objective The aim of this meta-analysis was to study the evidence on pain sensitization in knee osteoarthritis (OA), providing a quantitative synthesis of its prevalence and impact. Factors associated with pain sensitization were also investigated. Methods Meta-analysis; PubMed (MEDLINE), Cochrane Central Register (CENTRAL), and Web of Science were searched on February 2021. Level I to level IV studies evaluating the presence of pain sensitization in patients with symptomatic knee OA, documented through a validated method (questionnaires or quantitative sensory testing), were included. The primary outcome was the prevalence of pain sensitization. Factors influencing the prevalence were also evaluated, as well as differences in terms of pain thresholds between knee OA patients and healthy controls. Results Fifty-three articles including 7,117 patients were included. The meta-analysis of proportion documented a prevalence of pain sensitization of 20% (95% confidence interval [CI] = 16%-26%) with a significant heterogeneity of results (I-2 = 89%, P < 0.001). The diagnostic tool used was the main factor influencing the documented prevalence of pain sensitization (P = 0.01). Knee OA patients presented higher pain sensitivity compared with healthy controls, both in terms of local pressure pain threshold (standardized mean difference [SMD] = -1.00, 95% CI = -1.67 to -0.32, P = 0.007) and distant pressure pain threshold (SMD = -0.54, 95% CI = -0.76 to -0.31, P < 0.001). Conclusions Knee OA pain presents features that are consistent with a significant degree of pain sensitization. There is a high heterogeneity in the reported results, mainly based on the diagnostic tool used. The identification of the best methods to detect pain sensitization is warranted to correctly evaluate and manage symptoms of patients affected by knee OA. Registration: PROSPERO CRD42019123347

Pregabalin versus gabapentin nel trattamento dei pazienti con neuropatia periferica: adattamento di un modello internazionale per la valutazione di costo/efficacia e costo/utilità alla realtà nazionale

OBJECTIVE: To compare the economic impact of treating neuropathic pain with pregabalin versus gabapentin. DESIGN: A cost effectiveness analysis comparing costs and effects of pregabalin 375 mg/die versus gabapentin 1800 mg/die in the perspective of the Italian National Healthcare Service was developed. The cost effectiveness analysis is examined alternatively in terms of the incremental cost per additional day with no or mild pain, and the incremental cost per quality-adjusted life-year (QALY) gained. Effects were derived from a pregabalin randomised clinical study 1008-155 and gabapentin 645-210 and 945-211 studies. Effects are expressed as reduction score of the VAS pain scale. Pharmacological costs were quantified according to the Italian market price of the drugs; healthcare procedure and hospitalisation costs were quantified on the basis of the National Tariff. Other healthcare services consumption data were derived from a Delphi Panel. To estimate the impact of pregabalin and gabapentin on daily pain experience in patients with neuropatic pain a Markov model is used. The dynamic simulation focuses on a hypothetical cohort of 1000 patients and simulates their daily pain experience over 12 weeks, to estimate clinical and economic outcomes for the group as a whole. MAIN OUTCOME MEASURES AND RESULTS: The cost-effectiveness ratio for the use of pregabalin is less than 1 euro per additional day with no or mild pain and 468 euros per QALY. The sensitivity analysis conducted to examine the effects of decreasing gabapentin dose to 1200 mg/die showes the consistency of the model results. CONCLUSIONS AND RESULTS: Although pregabalin pure costs are higher than gabapentin costs, the analyses prove pregabalin to be more effective with a small additional cost per day with no or mild pain

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Tracker Operation and Performance at the Magnet Test and Cosmic Challenge

During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Pregabalin and other antiepileptic drugs in chronic neuropathic pain

Chronic pain resulting from nervous system injury is, in almost all cases, difficult to treat. In 1995 the first trial on the efficacy of gabapentin for neuropathic pain appeared. In 2004 pregabalin was introduced, approved as adjunctive therapy in epilepsy and the treatment of generalized anxiety disorder and peripheral and central neuropathic pain in adults (for example pain originating from post-herpetic neuralgia, neuropathy associated with neoplastic disease, post-stroke pain or spinal paralysis, polyneuropathy, multineuropathy, mononeuropathy, and painful diabetic neuropathy). Studies comparing the two drugs indicate a greater power of action of pregabalin with a dose efficacy ratio of 3 to 1. This allows pregabalin to be released at lower doses without the need of lengthy initial titration to achieve therapeutic range. The bioavailability of pregabalin is constant while that of gabapentin decreases with the dose; gabapentin bioavailability at 1600 mg is only 27% while for pregabalin bioavailability is > 90% at all doses. Pregabalin in direct comparison has proved clinically more effective than gabapentin and is also effective in patients unresponsive to gabapentin. Gabapentin absorption takes place only in the small intestine while that of pregabalin even in the ascending portion of the colon. This leads to a higher risk of gabapentin interactions with drugs affecting small intestine motility, such as opioids, often associated in pain therapy. For the same reason, patients with bowel resections benefit best from treatment with pregabalin

Peripheral and central presentation of neuropathic pain

Neuropathic pain is a pain originating within the peripheral or central nervous system and differs from nociceptive pain originated outside the nervous system. Pain due to disorders of the brain, however, originates also from abnormal interaction of cognitive and emotional pain processing brain areas. It might also arise from decreased activity of the hypothalamic and descending inhibitory pathways that are always at play both in physiological and pathological pain. To avoid the “grey zone” of such “functional pain states,” neurologists and neurophysiologists have confined the definition of neuropathic pain to “pain caused by injury or disease of the somatosensory system.” The present chapter adheres to this restrictive definition; however, it also describes painful conditions caused by strictly neurological disease such as spinal cord injury, restless legs syndrome, Parkinson’s disease and epilepsy that put forward the relevance of the descending inhibitory system into the generation of central neuropathic pain