Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study.

OBJECTIVES: To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain. METHODS: A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using "bedside tests" and Brief Pain Inventory (question 5). RESULTS: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12. CONCLUSIONS: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

Neuropathic pain.

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aß, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.

[The therapeutic use of D9-tetrahydrocannabinol (dronabinol) in refractory neuropathic pain]. / Utilisation thérapeutique du D9-tétrahydrocannabinol (dronabinol) dans les douleurs neuropathiques réfractaires.

INTRODUCTION: Despite the recent discovery of the potential mechanisms underlying the analgesic effects of cannabis, few clinical studies have so far assessed its analgesic effects, notably in the treatment of chronic non-malignant pain. All the studies used administration of cannabis alone. The aim of this open, pilot, study was to assess the efficacy and side effect profile of oral dronabinol (tetrahydrocannabinol - THC) in the treatment of refractory neuropathic pain. METHODS: Seven patients (3 women/4 men), aged 60 +/- 14 years, suffering from chronic refractory neuropathic pain, received oral THC titrated to the maximum dose of 25 mg/day (mean dose: 15 +/- 6 mg), during an average of 55,4 days (range: 13-128). Various components of pain (continuous, paroxysmal and brush-induced allodynia) were assessed using VAS scores. Health-related Quality of Life (HRQL) was evaluated using the Brief Pain Inventory, and the Hospital Anxiety and Depression scale was used to measure depression and anxiety. RESULTS: THC did not induce significant effect on the various pain, HRQL and anxiety and depression scores. Numerous side effects (notably sedation and asthenia) were observed in 5 patients out of 7, requiring premature discontinuation of the drug in 3 patients. CONCLUSION: The present study did not reveal any significant efficacy of THC in a small cohort of patients with chronic refractory neuropathic pain, but underlined the unfavorable side effect profile of the drug. These results may partly relate to the fact that oral dronabinol exhibits a poor therapeutic ratio (efficacy at the price of side effects). The development of new and better tolerated cannabinoids is warranted.