Mechanism-based pain diagnosis - Issues for analgesic drug development
Harvard University, Cambridge, Massachusetts, United StatesAnesthesiology (Impact Factor: 6.17). 08/2001; 95(1):241-9. DOI: 10.1097/00000542-200107000-00034
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ABSTRACT: Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. Patients received THC/CBD spray for a further 38 weeks in addition to their current analgesic therapy. Neuropathic pain severity was the primary efficacy measure using a pain 0-10 numerical rating scale (NRS). Additional efficacy, safety and tolerability outcomes were also investigated. In total, 234 patients completed the study (62 %). The pain NRS showed a decrease in score over time in patients from a mean of 6.9 points (baseline in the parent studies) to a mean of 4.2 points (end of open-label follow-up). The proportion of patients who reported at least a clinically relevant 30 % improvement in pain continued to increase with time (up to 9 months); at least half of all patients reported a 30 % improvement at all time points. Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.Journal of Neurology 09/2014; 262(1). DOI:10.1007/s00415-014-7502-9 · 3.84 Impact Factor
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ABSTRACT: Introduction: It is difficult to overestimate the personal and socioeconomic impact of chronic low back pain (CLBP). It is the leading cause of years lost to disability and poses the highest economic toll among chronic illnesses. Despite the strong need for extensive research efforts, few drugs have consistently demonstrated effectiveness for this condition. Areas covered: In this review, the epidemiology, rationale for mechanism-based treatment, competitive environment and market trends, and the preclinical and clinical evidence supporting over 15 different classes of analgesic medications studied for CLBP or related pain conditions are discussed. Treatments are divided by drug category, type of CLBP they are likely to treat (e.g., neuropathic or mechanical), and whether they are new formulations of existing treatments, new indications for existing treatments or represent novel mechanisms of action. Databases searched included MEDLINE, Embase, Pharmaprojects and various clinical trial registries. Expert opinion: Many barriers exist for the development of medications for CLBP including difficulties in identifying pathophysiological mechanisms, biologic resiliency secondary to multiple concurrent pain pathways and off-target and sometimes serious side effects. Nevertheless, the volume and diversity of novel molecular entities has continued to surge and includes possible disease-modifying therapies such as gene and stem cell therapy.Expert Opinion on Emerging Drugs 12/2014; 20(1):1-25. DOI:10.1517/14728214.2015.993379 · 3.28 Impact Factor
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