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Current therapies for Head and Neck cancer treatment are extremely advanced. Though, they cause oral complications which have deleterious effects on basic life functions, affect oral and overall health, may lead to significant morbidity and treatment discontinuation and have an impact on survivorship and quality of life. As new therapies are introduced, a new spectrum of oral complications is rising, compromising the mucosal integrity and the salivary function, that may not be recognized, reported and treated properly. Oral complications, often permanent and extremely painful, may include mucositis, xerostomia, dysgeusia, infections, trismus and fibrosis, risk of dental disease and necrosis of the jaw, neurosensory disorders and when targeted therapies and immunotherapy are involved, aphthoid and lichenoid lesions can also be reported. Increased awareness is required for the prevention and management of these complications, which can be best provided by a multidisciplinary team.

OBJECTIVES Neuropathic pain (NP) is a complex condition that impairs the patients' quality of life. Registries are useful tools, increasingly used as they provide high-quality data. This article aims to describe the Greek Neuropathic Pain Registry (Gr.NP.R.) design, the patients' baseline data, and real-world treatment outcomes. METHODS The Gr.NP.R. collects electronically, stores, and shares real-world clinical data from Pain and Palliative Care centers in Greece. It is a web-based application, which ensures security, simplicity, and transparency. VAS, DN4, and Pain Detect were used for pain and NP assessment. RESULTS From 2016 to 2020, 5980 patients with chronic pain, of cancer or non-cancer origin, were examined and 2334 fulfilled the NP inclusion criteria (VAS > 5, DN4 > 4, and Pain Detect ≥ 19). At the first visit, the mean age was 64.8 years, 65.5% were female patients, and 97.9% were Greek. The mean (SD) time from pain initiation to visiting the pain clinics was 1.5 (3.8) years. Most patients were undertreated. Following the patients' registration, the national guidelines were implemented. The majority of the prescribed medications were gabapentinoids (70.2%), especially pregabalin (62.6%), and opioids (tramadol, 55.3%). At visits 1 and 6, mean VAS was 7.1 and 5, and mean DN4 score was 5.6 and 3.5, respectively. CONCLUSIONS The Gr.NP.R. provides information on the demographics, clinical progress, treatment history, treatment responses, and the drugs of choice for patients with cancer and non-cancer NP. The collected data may help physicians plan the management of their patients.

Background: Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a treatment challenge. Most studies investigating drugs against NP are conducted in patients suffering with diabetic neuropathy or postherpetic neuralgia, while data are limited in cancer pain management. Additionally, regarding cancer therapy-related NP, most of the studies do not focus on HNC patients. The aim of this review is to identify the studies on systematically administered medication for NP management that included HNC patients under radiotherapy. Methods: A systematic literature search was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The medical subject heading (MeSH) terms were (“head and neck cancer” OR “tumor”) AND “neuropathic pain” AND “medication” AND “radiotherapy.” The Cochrane Collaboration tool was used for quality assessment. Results: The search identified 432 articles. Three more articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles met the eligibility inclusion criteria and were included in this review; 6 on gabapentin, 1 on pregabalin, 1 on nortriptyline, 1 on methadone, and 1 on ketamine. Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies on pregabalin (p = 0.003), methadone (p = 0.03), ketamine (p = 0.012), and in two out of six gabapentin studies (p < 0.004). Two of the studies (both concerning gabapentin) had no comparison arm. Conclusions: Treatments including pregabalin, methadone, ketamine, and gabapentin were found to provide pain relief against HNC NP. While there is a plethora of pharmacological treatments available for the management of NP, only a few studies have been conducted regarding the pharmacological management of therapy-related NP in HNC patients. More studies should be conducted regarding the pharmacological approaches in HNC therapy-related NP so that specific treatment algorithms can be developed.

Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host's response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.

Objectives Neuropathic pain (NP) is a complex condition that impairs the patients’ quality of life. Registries are useful tools, increasingly used as they provide high-quality data. This article aims to describe the Greek Neuropathic Pain Registry (Gr.NP.R.) design, the patients’ baseline data, and real-world treatment outcomes. Methods The Gr.NP.R. collects electronically, stores, and shares real-world clinical data from Pain and Palliative Care centers in Greece. It is a web-based application, which ensures security, simplicity, and transparency. VAS, DN4, and Pain Detect were used for pain and NP assessment. Results From 2016 to 2020, 5980 patients with chronic pain, of cancer or non-cancer origin, were examined and 2334 fulfilled the NP inclusion criteria (VAS > 5, DN4 > 4, and Pain Detect >= 19). At the first visit, the mean age was 64.8 years, 65.5% were female patients, and 97.9% were Greek. The mean (SD) time from pain initiation to visiting the pain clinics was 1.5 (3.8) years. Most patients were undertreated. Following the patients’ registration, the national guidelines were implemented. The majority of the prescribed medications were gabapentinoids (70.2%), especially pregabalin (62.6%), and opioids (tramadol, 55.3%). At visits 1 and 6, mean VAS was 7.1 and 5, and mean DN4 score was 5.6 and 3.5, respectively. Conclusions The Gr.NP.R. provides information on the demographics, clinical progress, treatment history, treatment responses, and the drugs of choice for patients with cancer and non-cancer NP. The collected data may help physicians plan the management of their patients.

Pain due to oral-mucositis (OM) in head and neck cancer (HNC) patients receiving radiotherapy (RT) /chemo-radiotherapy (CRT) can be nociceptive and/or neuropathic. Neuropathic pain (NP) often remains underdiagnosed and untreated. This study's purpose was to identify the presence of OM-induced NP in HNC patients under RT/CRT.Pain was assessed using a 0-10 numeric scale (NRS). At an NRS≥5 score, patients completed the Douleur Neuropathique 4 (DN4) questionnaire, where a score ≥4/10 indicates the presence of NP. Mucositis and xerostomia were assessed using the European Organization for Research and Treatment of Cancer and the NRS scales accordingly. Pain medication was documented.Forty patients were recruited; twenty-six (mean age 63.54±13.96 years) completed a DN4 (mean pain NRS 7.46±1.42); five (5/26, 19.23%) had a DN4≥4. The most common NP descriptors were "burning" (34.62%), "electric shocks" (30.77%) and "pins-and-needles" (30.77%). A direct correlation was observed between DN4 and pain, mucositis, and xerostomia (p0.02). Pain medication was administered to fifteen patients (15/26, 57.69%). Adjuvant medication was administered to one patient with positive DN4 score.Five (5/26, 19%) of the patients with NRS≥5 developed NP; adjuvant medication to address NP was prescribed to one patient. NP is likely underdiagnosed and undertreated in the HNC population undergoing RT/RC.

Purpose: The Patient Neurotoxicity Questionnaire (PNQ) represents a diagnostic tool concerning patients with chemotherapy-induced peripheral neuropathy (CIPN). The application of such a tool in the Greek clinical praxis requires validation. Methods: Validation consists of three stages - translation, reverse translation, and patient application. Hundred oncologic patients were assessed by comparing the PNQ to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) at the chemotherapy onset and second, fourth, and sixth sessions. The diagnostic tool's specific requirements (compliance, validity, concordance, sensitivity, specificity, reliability) were statistically evaluated. Results: Differences between translated texts and between the reverse translation and the original were considered negligible. At the second, fourth, and sixth session compliance was 98%, 95%, and 93% while Cronbach’s α was 0,57 0,69, and 0,81, respectively. Cohen’s weighted κ was 0,67 and 0,58, Spearman’s ρ was 0,7 and 0,98, while the area under the curve (AUC) of the receiver operating characteristic (ROC) was 1 and 0,9 for the sensory and the motor part, respectively. The variance’s linear regression analysis confirmed CIPN worsening over time (P

Purpose: The Patient Neurotoxicity Questionnaire (PNQ) represents a diagnostic tool concerning patients with chemotherapy-induced peripheral neuropathy (CIPN). The application of such a tool in the Greek clinical praxis requires validation. Methods: Validation consists of three stages - translation, reverse translation, and patient application. Hundred oncologic patients were assessed by comparing the PNQ to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) at the chemotherapy onset and second, fourth, and sixth sessions. The diagnostic tool’s specific requirements (compliance, validity, concordance, sensitivity, specificity, reliability) were statistically evaluated. Results: Differences between translated texts and between the reverse translation and the original were considered negligible. At the second, fourth, and sixth session compliance was 98%, 95%, and 93% while Cronbach’s a was 0,57 0,69, and 0,81, respectively. Cohen’s weighted. was 0,67 and 0,58, Spearman’s. was 0,7 and 0,98, while the area under the curve (AUC) of the receiver operating characteristic (ROC) was 1 and 0,9 for the sensory and the motor part, respectively. The variance’s linear regression analysis confirmed CIPN worsening over time (P

Current therapies for Head and Neck cancer treatment are extremely advanced. Though, they cause oral complications which have deleterious effects on basic life functions, affect oral and overall health, may lead to significant morbidity and treatment discontinuation and have an impact on survivorship and quality of life. As new therapies are introduced, a new spectrum of oral complications is rising, compromising the mucosal integrity and the salivary function, that may not be recognized, reported and treated properly. Oral complications, often permanent and extremely painful, may include mucositis, xerostomia, dysgeusia, infections, trismus and fibrosis, risk of dental disease and necrosis of the jaw, neurosensory disorders and when targeted therapies and immunotherapy are involved, aphthoid and lichenoid lesions can also be reported. Increased awareness is required for the prevention and management of these complications, which can be best provided by a multidisciplinary team. © 2021 Maria Kouri et al., published by Sciendo 2021.

Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN). A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review. The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN. Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.

Peripheral neuropathic pain (PNP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a lesion or disease affecting the peripheral nervous system. PNP is associated with a remarkable disease burden, and there is an increasing demand for new therapies to be used in isolation or combination with currently available treatments. The aim of this systematic review was to evaluate the current evidence, derived from randomized controlled trials (RCTs) that assess non-pharmacological interventions for the treatment of PNP.After a systematic Medline search, we identified 18 papers eligible to be included.The currently best available evidence (level II of evidence) exist for painful diabetic peripheral neuropathy. In particular, spinal cord stimulation as adjuvant to conventional medical treatment can be effectively used for the management of patients with refractory pain. Similarly, adjuvant repetitive transcranial magnetic stimulation of the motor cortex is effective in reducing the overall pain intensity, whereas adjuvant static magnetic field therapy can lead to a significant decrease in exercise-induced pain. Weaker evidence (level III of evidence) exists for the use of acupuncture as a monotherapy and neurofeedback, either as an add-on or a monotherapy approach, for treatment of painful chemotherapy-induced peripheral neuropathy CONCLUSIONS: Future RCTs should be conducted to shed more light in the use of non-pharmacological approaches in patients with PNP.

Introduction Central post-stroke pain (CPSP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a cerebrovascular event and is a result of central lesions of the somatosensory tract. The aim of this systematic review and meta-analysis was to establish the prevalence of CPSP, to describe its characteristics, and to discuss the associated management challenges. Methods After a systematic Medline search, we identified 69 papers eligible to be included. Results The pooled prevalence of CPSP in patients with stroke at any location was 11% (95% CI 7–18%), which can increase to more than 50% in the subgroups of patients with medullary or thalamic strokes. CPSP onset coincides with stroke occurrence in 26% of patients (95% CI 18–35%); CPSP manifests within a month since symptom onset in 31% of patients (95% CI 22–42%), and occurs between the first month and the first year in 41% of patients (95% CI 33.9–49.0%). CPSP develops more than 12 months after stroke onset in 5% of patients (95% CI 3–8%). Conclusions Clinicians should look for any evidence of central neuropathic pain for at least 12 months after stroke. Both pharmacological and non-pharmacological interventions can be used for the management of CPSP. Lamotrigine has the strongest evidence (Level II of evidence, derived from small randomized controlled trials) for being effective in the management of CPSP. Future research should focus on well-designed trials of pharmacological and non-pharmacological interventions aiming to relief CPSP, which is a very common but often neglected pain syndrome. Electronic supplementary material The online version of this article (10.1007/s12325-020-01388-w) contains supplementary material, which is available to authorized users.