Revisiting topical therapies in neuropathic pain: Lessons from guidelines and clinical practice.

Neuropathic pain is reported to be common based on studies from specialty centers and survey studies. However, few prevalence estimates have been completed in a community population using clinical evaluation. To develop an estimate of the prevalence of neuropathic pain in community-dwelling adults. Data from a mailed survey (N = 3,575 community respondents), telephone interview (N = 907), and a clinical examination (N = 205) were linked to estimate the population prevalence of neuropathic pain. Using the clinical examination as the "gold" standard, estimates from several screening tools were developed and adjusted to the Olmsted County, MN adult population. The estimated community prevalence of neuropathic pain from the clinical examination (gold standard) was 9.8%. Most other estimates were lower, including a 3.0% population prevalence using the Berger criteria and 8.8% using the Leeds Assessment of Neuropathic Symptoms and Signs. Only the prevalence rate based on self-report of nerve pain was higher (12.4%). Overlap among the groups each tool identified as having "neuropathic predominant pain" was only modest and the groups had significantly different rates of depressive symptoms, anxiety, limited functional ability, and use of complementary and alternative medicine. The estimated rates and personal characteristics of community residents with "neuropathic pain" vary widely depending on the tools used to identify neuropathic pain. None of the screening tools compared well with clinical evaluation. The differences in the groups identified by alternative screening methods become of major importance when reporting neuropathic pain epidemiology, studying therapies for neuropathic pain, or attempting to translate neuropathic pain research into clinical practice.

Capsaicin 8% patch as therapy for neuropathic chronic postsurgical pain after melanoma excision surgery: A single center case series

SP66 Chemotherapy induced neuropathic pain. Clinical diagnosis and treatment

Background:Neuropathic pain is one of the more severe types of chronic pain and presents a great challenge as response to medical therapy remains often unpredictable. With the opioid epidemic and the search for ways to avoid narcotics, physicians are seeking other modalities to treat neuropathic pain. In recent years, surgeons have explored various surgical avenues to improve outcomes. The aim of this review was to evaluate the current clinical evidence regarding the efficacy of fat grafting for the treatment of neuropathic pain.Methods:A critical review was conducted to examine the current clinical evidence of fat grafting as a therapy for neuropathic pain caused by neuromas, peripheral neuralgia, migraine and headaches, neuropathic scar pain, and postmastectomy pain syndrome.Results:The precise mechanism role of fat grafting in modulating neuropathic pain remains unclear, but it appears to reduce pain levels through the anti-inflammatory effects of adipose-derived stem cells and mechanical cushioning by fat.Conclusions:Fat grafting is an emerging therapy for chronic neuropathic pain of various etiologies. Although promising results have been reported, sample size and level of evidence of current studies are low. The encouraging results, however, are worthy of further clinical and scientific study. The minimally invasive nature of fat grafting and favorable risk profile make this an attractive therapy for neuropathic pain.

This meeting report highlights the main topics presented at the conference "Chronic Inflammatory and Neuropathic Pain," convened jointly by the New York Academy of Sciences, MedImmune, and Grünenthal GmbH, on June 2-3, 2011, with the goal of providing a conducive environment for lively, informed, and synergistic conversation among participants from academia, industry, clinical practice, and government to explore new frontiers in our understanding and treatment of chronic and neuropathic pain. The program included leading and emerging investigators studying the pathophysiological mechanisms underlying neuropathic and chronic pain, and experts in the clinical development of pain therapies. Discussion included novel issues, current challenges, and future directions of basic research in pain and preclinical and clinical development of new therapies for chronic pain.

Confirming neuropathic pain in cancer patients: Applying the NeuPSIG grading system in clinical practice and clinical research

Background and aims In 2008, the International Association for the Study of Pain Special Interest Group on Neuropathic Pain (NeuPSIG) proposed a clinical grading system to help identify patients with neuropathic pain (NeP). We previously applied this classification system, along with two NeP screening tools, the painDETECT (PD-Q) and Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS), to identify NeP in patients with neck/upper limb pain. Both screening tools failed to identify a large proportion of patients with clinically classified NeP, however a limitation of our study was the use of a single clinician performing the NeP classification. In 2016, the NeuPSIG grading system was updated with the aim of improving its clinical utility. We were interested in field testing of the revised grading system, in particular in the application of the grading system and the agreement of interpretation of clinical findings. The primary aim of the current study was to explore the application of the NeuPSIG revised grading system based on patient records and to establish the inter-rater agreement of detecting NeP. A secondary aim was to investigate the level of agreement in detecting NeP between the revised NeuPSIG grading system and the LANSS and PD-Q. Methods In this retrospective study, two expert clinicians (Specialist Pain Medicine Physician and Advanced Scope Physiotherapist) independently reviewed 152 patient case notes and classified them according to the revised grading system. The consensus of the expert clinicians' clinical classification was used as "gold standard" to determine the diagnostic accuracy of the two NeP screening tools. Results The two clinicians agreed in classifying 117 out of 152 patients (ICC 0.794, 95% CI 0.716-850; κ 0.62, 95% CI 0.50-0.73), yielding a 77% agreement. Compared to the clinicians' consensus, both LANSS and PD-Q demonstrated limited diagnostic accuracy in detecting NeP (LANSS sensitivity 24%, specificity 97%; PD-Q sensitivity 53%, specificity 67%). Conclusions The application of the revised NeP grading system was feasible in our retrospective analysis of patients with neck/upper limb pain. High inter-rater percentage agreement was demonstrated. The hierarchical order of classification may lead to false negative classification. We propose that in the absence of sensory changes or diagnostic tests in patients with neck/upper limb pain, classification of NeP may be further improved using a cluster of clinical findings that confirm a relevant nerve lesion/disease, such as reflex and motor changes. The diagnostic accuracy of LANSS and PD-Q in identifying NeP in patients with neck/upper limb pain remains limited. Clinical judgment remains crucial to diagnosing NeP in the clinical practice. Implications Our observations suggest that in view of the heterogeneity in patients with neck/upper limb pain, a considerable amount of expertise is required to interpret the revised grading system. While the application was feasible in our clinical setting, it is unclear if this will be feasible to apply in primary health care settings where early recognition and timely intervention is often most needed. The use of LANSS and PD-Q in the identification of NeP in patients with neck/upper limb pain remains questionable.

Mexiletine as an adjuvant analgesic for the management of neuropathic cancer pain.

ObjectiveMesenchymal stem cells (MSCs) have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i) injections of autologous MSCs can reduce human neuropathic pain and ii) evaluate the safety of the procedure.MethodsTen subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i) pain intensity measured by standard numerical rating scale from 0–10 and ii) daily dosage requirements of antineuropathic pain medication.ResultsSubjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years) with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites). Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58) and at 6 months had decreased to 4.3 (SD 3.28), P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student’s t-test).ConclusionThis preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain significantly reduced pain intensity at 6 months and is a safe and well tolerated intervention.

Neuropathic cancer pain (NCP), commonly encountered in clinical practice, may be cancer-related, namely resulting from nervous system tumor invasion, surgical nerve damage during tumor removal, radiation-induced nerve damage and chemotherapy-related neuropathy, or may be of benign origin, unrelated to cancer. A neuropathic component is evident in about 1/3 of cancer pain cases. Although from a pathophysiological perspective NCP may differ from chronic neuropathic pain (NP), such as noncancer-related pain, clinical practice, and limited publications have shown that these two pain entities may share some treatment modalities. For example, co-analgesics have been well integrated into cancer pain-management strategies and are often used as First-Line options for the treatment of NCP. These drugs, including antidepressants and anticonvulsants, are recommended by evidence-based guidelines, whereas, others such as lidocaine patch 5%, are supported by randomized, controlled, clinical data and are included in guidelines for restricted conditions treatment. The vast majority of these drugs have already been proven useful in the management of benign NP syndromes. Treatment decisions for patients with NP can be difficult. The intrinsic difficulties in performing randomized controlled trials in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign NP for the management of malignant NP, despite the lack of relevant high quality data. Interest in NCP mechanisms and pharmacotherapy has increased, resulting in significant mechanism-based treatment advances for the future. In this comprehensive review, we present the latest knowledge regarding NCP pharmacological management.

Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain (n = 22), neuropathic pain (n = 18), neuritis (nociceptive pain) (n = 4), or no pain (n = 17), further to those with diabetic neuropathy and neuropathic pain (n = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1β, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-β were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group (p = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1β, TNF, TGF-β, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1β levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1β is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.

Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews

In recent years, medical gas therapy has emerged as a promising approach for treating neuropathic pain. This review article aimed to investigate the therapeutic effects of medical gas therapy on neuropathic pain and its underlying mechanisms, thereby providing a theoretical foundation for clinical practice. A literature search was conducted using the Web of Science Core Collection database. Co-occurrence analysis of keywords revealed that terms including "neuropathic pain," "nitric oxide," "nitric oxide synthase," "pain," and "ozone" frequently appeared. Cluster analysis grouped these keywords into four primary categories: intervertebral disc disease and gas therapy, mechanisms of neuropathic pain and gas interventions, the role of nitric oxide in modulating neuropathic pain and gas therapy, and the effects of gas therapy on mental disorders in the context of neuropathic pain treatment. The analysis of highly cited literature in the field of medical gas therapy for neuropathic pain emphasizes the crucial roles of nitric oxide and nitric oxide synthase in nerve injury and pain. Various types of gas therapy, including oxygen-ozone therapy and nitric oxide-related therapies, show promise in treating pain following peripheral nerve injury. Oxidative stress and nitric oxide are crucial regulatory factors in the pain signaling associated with trigeminal neuralgia. Ozone therapy alleviates trigeminal pain by inhibiting inflammatory responses, reducing oxidative stress, and modulating neurotransmitter release. Novel nanomaterials, such as manganese oxide nanoparticles, have also demonstrated potential in scavenging free radicals and alleviating sciatic nerve pain. Ozone therapy has shown good clinical efficacy in treating lumbar disc herniation and sciatica, whereas both ozone therapy and hyperbaric oxygen therapy have demonstrated effectiveness and safety in managing postherpetic neuralgia. In conclusion, medical gas therapy for neuropathic pain primarily includes oxygen-ozone therapy, nitric oxide-related therapies, hydrogen sulfide-related therapies, and hyperbaric oxygen therapy. While these therapies exhibit efficacy in managing neuropathic pain, further research is necessary to elucidate their mechanisms of action and safety profiles. Although hyperbaric oxygen therapy and ozone therapy have already been implemented in clinical research, other types of gas therapy are still in the animal testing phase. Therefore, future studies should focus on conducting more multicenter, large-sample randomized controlled trials to accelerate clinical translation and provide more effective treatment options for patients suffering from neuropathic pain.

Topical Analgesic Combinations for Bortezomib Neuropathy

Background Chronic neuropathic pain is a common occurrence, its prevalence ranges from 7 to 10% of the total population. Currently, the only official document that includes neuropathic pain is the International Classification of Headaches Disorders (ICHD-3), in which this type of pain is associated with traumatic brain injury and neuralgia. Until now, there has been no generally accepted terminology and classification of chronic neuropathic pain.Objective To provide the current terminology, classification and additional characteristics of neuropathic chronic pain.Results The review of modern terminology and classification of neuropathic chronic pain describes the terms included in the concept of chronic peripheral and central neuropathic pain, identifies pain subtypes, as well as its additional characteristics such as the intensity of neuropathic pain, the severity of suffering and disability.Conclusions Thus, the presented recent classification of chronic neuropathic pain is an exhaustive list of the most common neuropathic pain syndromes. The inclusion of classification into clinical practice will help to draw attention to the problem of treatment of chronic neuropathic pain by WHO members, carrying out epidemiological studies and making a correct diagnosis, and therefore the appointment of adequate treatment methods.