Cannabinoides y dolor

Canabinoides como farmacoterapia para el dolor neuropático: desde el laboratorio a la clínica  Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Rahn EJ, Hohmann AG. Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, Georgia 30602, USA. Neurotherapeutics. 2009 Oct;6(4):713-37. Abstract Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need. Here, we review studies evaluating cannabinoids for neuropathic pain management in the clinical and preclinical literature. Neuropathic pain associated with nerve injury, diabetes, chemotherapeutic treatment, human immunodeficiency virus, multiple sclerosis, and herpes zoster infection is considered. In animals, cannabinoids attenuate neuropathic nociception produced by traumatic nerve injury, disease, and toxic insults. Effects of mixed cannabinoid CB(1)/CB(2) agonists, CB(2) selective agonists, and modulators of the endocannabinoid system (i.e., inhibitors of transport or degradation) are compared. Effects of genetic disruption of cannabinoid receptors or enzymes controlling endocannabinoid degradation on neuropathic nociception are described. Specific forms of allodynia and hyperalgesia modulated by cannabinoids are also considered. In humans, effects of smoked marijuana, synthetic Delta(9)-THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both Delta(9)-THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment. Subjective (i.e., rating scales) and objective (i.e., stimulus-evoked) measures of pain and quality of life are considered. Finally, limitations of cannabinoid pharmacotherapies are discussed together with directions for future research. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755639/?tool=pubmed http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755639/pdf/nihms141302.pdf    Canabinoides en el dolor de difícil manejo Cannabinoids in the management of difficult to treat pain. Russo EB. GW Pharmaceuticals Vashon, WA, USA. Ther Clin Risk Manag. 2008 Feb;4(1):245-59. Abstract This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/?tool=pubmed http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/pdf/tcrm-0401-245.pdf Papel del sistema canabinoide en el tratamiento e implicaciones para el manejo de los episodios de dolor agudo y crónico  Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Manzanares J, Julian M, Carrascosa A. Instituto de Neurociencias de Alicante, Universidad Miguel Hernandez-Consejo Superior de Investigaciones Cientificas, Apartado de correos 18, 03550 Sant Joan d'Alacant, Spain. jmanzanares@umh.es Curr Neuropharmacol. 2006 Jul;4(3):239-57. Abstract Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB(1)mediated suppression of mast cell activation responses, CB(2)-mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/?tool=pubmed http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/pdf/CN-4-3-239.pdf

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