Perineural injections of incobotulinumtoxin-A for diabetic neuropathic pain of the lower extremities: protocol for a phase II, single-centre, double-blind, randomised, placebo-controlled trial (the PINBOT study).

INTRODUCTION: Diabetic neuropathic pain (DNP) is a debilitating complication affecting 15-20% of people with diabetes and is a predictor of depression, poor sleep and decreased quality of life. Current pharmacological treatments are often insufficient and have significant side-effects. Subcutaneous or intradermal botulinumtoxin-A (BonT-A) is an effective and safe treatment for neuropathic pain but is limited by the need to cover the entire affected area with injections. For large cutaneous areas, infiltration of the sensory nerve supply with BonT-A could provide similar effects, with a single injection. We aim to investigate the safety, efficacy, and effects on quality of life, physical activity, depressive symptoms and activities of daily living of perineural injections of BonT-A in patients with DNP of both lower extremities. METHODS: This study is a double-blind, randomised, placebo-controlled clinical trial. 80 participants with moderate to severe DNP of both legs will be randomised 1:1 to receive injections of either 100 units incobotulinumtoxin-A or a saline placebo around each distal sciatic nerve for two cycles of 12 weeks. Average daily pain scores will be recorded once a day from 1 week prior to the first treatment and through the entire study period. Primary outcomes are differences between groups in daily and weekly mean pain scores. Secondary outcomes are levels of physical activity, depression scores, health-related quality of life, activities of daily living, sensory profiles and motor function, recorded at baseline, 4, 12, 16 and 24 weeks. The use of rescue medication and adverse events will be recorded throughout the study period. ETHICS AND DISSEMINATION: The study is approved by the Danish Committee on Health Research Ethics and the Danish Medicines Agency. EU-Clinical Trial Information System (EU: 2022-500727-68-01), clinicaltrials.gov (ID: NCT05623111). Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05623111.

Oral capsules of tetra-hydro-cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment.

BACKGROUND: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is 'weak against'. OBJECTIVES: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. METHODS: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5-50 mg, THC 2.5-25 mg, and CBD/THC 5 mg/2.5 mg-50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. RESULTS: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04-0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11-2.19), THC 0.38 (CI -0.65 to 1.4) and CBD/THC -0.12 (-1.13 to 0.89). CONCLUSIONS: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.

Socio-Demographics, Pain Characteristics, Quality of Life and Treatment Values Before and After Specialized Interdisciplinary Pain Treatment: Results from the Danish Clinical Pain Registry (PainData).

BACKGROUND AND AIMS: PainData is an electronic internet-based clinical pain registry established to improve the understanding and treatment of high-impact chronic pain. The primary aim of this paper is to describe socio-demographics, pain characteristics, quality of life, and treatment values at baseline and follow-up in individuals referred to public and private interdisciplinary pain centers in Denmark between 2018 and 2020. METHODS: Self-reported patient-reported outcomes collected through PainData before (n=12,257) and after (n=4,111) treatment across 13 public and private interdisciplinary specialized pain centers in Denmark (87% of all pain centers in Denmark) are described. RESULTS: Mean duration of pain was 10 years, and one in three patients reported chronic widespread pain. More than 40% reported opioid use, and 50% had tried four or more different treatment modalities prior to referral. More than 60% reported poor sleep, severe fatigue, and memory and/or concentration deficits. Mean scores on pain catastrophizing, fear of movement, and pain-related disability were high, whereas scores on pain acceptance and self-efficacy were low. Physical and mental health were rated as poor and fair, respectively. One in four patients reported being very much improved or much improved after treatment. Items commonly reported after treatment were increased knowledge about pain, emotions and mood (66.5%), being better at accepting life with chronic pain (63.1%), and improved activity pacing (60.6%). CONCLUSION: The PainData registry, containing data from a large cohort of individuals, can help to improve the understanding and treatment of high-impact chronic pain, and collaborations with other researchers are welcome.

[Cannabinoids for neuropathic pain management].

Pharmacological treatment of neuropathic pain is associated with side effects and limited efficacy. Recently, the interest in cannabis-based medicine has led to legalisation of medical cannabis in some countries. The aim of this review is to evaluate the evidence of cannabinoids in neuropathic pain. Seventeen trials were identified; eight reported an analgesic efficacy of cannabis-based medicine, and the remaining trials showed no analgesic efficacy. Conclusions were limited by design of studies and short duration of treatment. Overall, the reduction in pain was minimal.

Prevalence of neuropathic pain according to the IASP grading system in patients with chronic non-malignant pain.

OBJECTIVE: The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. SETTING: A Multidisciplinary Pain Center. SUBJECTS: One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. METHODS: Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. RESULTS: According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. CONCLUSIONS: According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire.

[Long term effect of spinal cord stimulation in a patient with complex regional pain syndrome and phantom pain syndrome type 1 after amputation]. / Langtidsbehandling med spinal cord-stimulation hos en patient med kronisk regionalt smertesyndrom type 1 og fantomsmerter efter amputation.

The development of stump and phantom pain after limb amputation in patients with complex regional pain syndrome (CRPS) is very frequent. Stump pain is typically recurred CRPS and the possibilities for effective pharmacological pain relief are often limited. Spinal cord stimulation (SCS) has a well-documented pain relieving effect in patients with CRPS. This case story summarises the long term effect of SCS in a patient with CRPS after two amputations of the right leg. Pharmacological pain therapies as well as Guanethidine blockade were found to be ineffective.