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Orexin as a target for pain It has been estimated that 9% of the US population suffers from moderate to severe non-cancer-related pain. Acute pain resulting from conditions such as headache, muscle spasms, dental problems or following surgery, affects 90 million Americans every year. Chronic pain is more troubling as it sparks a viscous cycle of clinical problems and often precipitates depression and/or life-style changes. Furthermore, establishing prolonged analgesia, free of serious side effects is a particularly challenging area of medicine. Estimates of the number of Americans suffering chronic pain range from 40-70 million. The most common types of non-cancer related chronic pain includes headache (40 million), arthritis (20 million) and lower back pain (40 million). The total economic cost of pain is $100 (US) billion in the US alone and the estimated worldwide market for pain and inflammation treatments has been estimated as $18.7 (US) billion worldwide. It is therefore not surprising that the development of analgesics has represented a major pharmaceutical objective. (click here for "Pain 2002" an analysis of future directions in analgesic therapeutics). Japanese researchers have recently described one novel analgesic target, orexin-A and its receptor orexin-1. Orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) are hypothalamic peptides and regulate feeding behavior, energy metabolism and the sleep-wake cycle. Orexin-A binds equally to both orexin-1 and orexin-2 receptors, while orexin-B has a preferential affinity for orexin-2 receptors. Orexins are concentrated in superficial laminae of the spinal dorsal horn, and orexin-A and orexin-1 receptors are found in the dorsal root ganglion cells implicating both proteins in pain pathways. Furthermore, intrathecal injection of orexin-A, but not orexin-B, suppressed the expression of Fos-like immunoreactivity (Fos-LI) in laminae I-II of L4-5 of the spinal cord and also displayed therapeutic activity in the formalin and hot plate assays. These effects of orexin-A were completely antagonized by pre-treatment with SB-334867, a selective orexin-1 receptor antagonist. These data are similar to those published last year by SKB researchers and further support the development of orexin-1 agonists for the treatment of pain
November, 2002 Adapted from Yamamoto et al, Br J Pharmacol 2002 Sep;137(2):170-6 Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
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