Cruzando la barrera del dolor: receptores P2 como blancos de nuevos analgésicos
Crossing the pain barrier: P2 receptors as targets for novel analgesics.
Kennedy C, Assis TS, Currie AJ, Rowan EG.
Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, John Arbuthnott Building, 27 Taylor Street, Glasgow G4 0NR, UK. c.kennedy@strath.ac.uk
J Physiol. 2003 Dec 15;553(Pt 3):683-94. Epub 2003 Sep 26.
Abstract
In 1995 the P2X3 receptor was found to be expressed at high levels in nociceptive sensory neurones, consistent with earlier reports that ATP induced pain in humans and animals. At first it was thought that ATP was most likely to play a role in acute pain, following its release from damaged or stressed cells and since then a wide variety of experimental techniques and approaches have been used to study this possibility. Whilst it is clear that exogenous and endogenous ATP can indeed acutely stimulate sensory neurones, more recent reports using gene knockout and antisense oligonucleotide technologies, and a novel, selective P2X3 antagonist, A-317491, all indicate that ATP and P2X3 receptors are more likely to be involved in chronic pain conditions, particularly chronic inflammatory and neuropathic pain. These reports indicate that P2X3 receptors on sensory nerves may be tonically activated by ATP released from nearby damaged or stressed cells, or perhaps from the sensory nerves themselves. This signal, when transmitted to the CNS, will be perceived consciously as chronic pain. In addition, it is now clear that several subtypes of P2Y receptor are also expressed in sensory neurones. Although their distribution and functions have not been as widely studied as P2X receptors, the effects that they mediate indicate that they might also be considered as therapeutic targets in the treatment of pain. Although our ability to treat persistent painful conditions, such as chronic inflammatory and neuropathic pain, has improved in recent years, these conditions are often resistant to currently available therapies, such as opioids or non-steroidal anti-inflammatory drugs. This reflects a limited understanding of the underlying pathophysiology. It is now clear that the development and maintenance of chronic pain are mediated by multiple factors, but many of these factors, and the receptors and mechanisms through which they act, remain to be identified. Chronic pain is debilitating and can greatly decrease quality of life, not just due to the pain per se, but also because of the depression that can often ensue. Thus a greater understanding of the mechanisms that underlie chronic pain will help identify new targets for novel analgesics, which will be of great therapeutic benefit to many people.
http://jp.physoc.org/content/553/3/683.full.pdf+html
Los canales de calcio dependientes de voltaje como objetivo para controlar el dolor neuropático
Targeting voltage-gated calcium channels for neuropathic pain management.
Perret D, Luo ZD.
Department of Anesthesiology & Perioperative Care, School of Medicine, University of California Irvine, Irvine, California 92697, USA.
Neurotherapeutics. 2009 Oct;6(4):679-92.
Abstract
Voltage-gated calcium channels (VGCC) play obligatory roles in diverse physiological functions. Pathological conditions leading to changes in their biophysical properties and expression levels may cause malfunctions of VGCC-mediated activities, resulting in disease states. It is believed that changes in VGCC properties under pain-inducing conditions may play a causal role in the development of chronic pain, including nerve injury-induced pain or neuropathic pain. For the past several decades, preclinical and clinical research in developing VGCC blockers or modulators for chronic pain management has been fruitful, leading to some U.S. Food and Drug Administration-approved drugs currently available for chronic pain management. However, their efficacy in pain relief is limited in some patients, and their long-term use is limited by their side-effect profiles. Certainly, there is room for improvement in developing more subtype-specific VGCC blockers or modulators for chronic pain conditions. In this review, we summarized the most recent preclinical and clinical studies related to chronic pain medications acting on the VGCC. We also included clinical trials aiming to expand the application of approved VGCC drugs to different pain states derived from various pathological conditions, as well as drug combination therapies trying to improve the efficacies and side-effect profiles of current pain medications.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755636/pdf/nihms133252.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
Crossing the pain barrier: P2 receptors as targets for novel analgesics.
Kennedy C, Assis TS, Currie AJ, Rowan EG.
Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, John Arbuthnott Building, 27 Taylor Street, Glasgow G4 0NR, UK. c.kennedy@strath.ac.uk
J Physiol. 2003 Dec 15;553(Pt 3):683-94. Epub 2003 Sep 26.
Abstract
In 1995 the P2X3 receptor was found to be expressed at high levels in nociceptive sensory neurones, consistent with earlier reports that ATP induced pain in humans and animals. At first it was thought that ATP was most likely to play a role in acute pain, following its release from damaged or stressed cells and since then a wide variety of experimental techniques and approaches have been used to study this possibility. Whilst it is clear that exogenous and endogenous ATP can indeed acutely stimulate sensory neurones, more recent reports using gene knockout and antisense oligonucleotide technologies, and a novel, selective P2X3 antagonist, A-317491, all indicate that ATP and P2X3 receptors are more likely to be involved in chronic pain conditions, particularly chronic inflammatory and neuropathic pain. These reports indicate that P2X3 receptors on sensory nerves may be tonically activated by ATP released from nearby damaged or stressed cells, or perhaps from the sensory nerves themselves. This signal, when transmitted to the CNS, will be perceived consciously as chronic pain. In addition, it is now clear that several subtypes of P2Y receptor are also expressed in sensory neurones. Although their distribution and functions have not been as widely studied as P2X receptors, the effects that they mediate indicate that they might also be considered as therapeutic targets in the treatment of pain. Although our ability to treat persistent painful conditions, such as chronic inflammatory and neuropathic pain, has improved in recent years, these conditions are often resistant to currently available therapies, such as opioids or non-steroidal anti-inflammatory drugs. This reflects a limited understanding of the underlying pathophysiology. It is now clear that the development and maintenance of chronic pain are mediated by multiple factors, but many of these factors, and the receptors and mechanisms through which they act, remain to be identified. Chronic pain is debilitating and can greatly decrease quality of life, not just due to the pain per se, but also because of the depression that can often ensue. Thus a greater understanding of the mechanisms that underlie chronic pain will help identify new targets for novel analgesics, which will be of great therapeutic benefit to many people.
http://jp.physoc.org/content/553/3/683.full.pdf+html
Los canales de calcio dependientes de voltaje como objetivo para controlar el dolor neuropático
Targeting voltage-gated calcium channels for neuropathic pain management.
Perret D, Luo ZD.
Department of Anesthesiology & Perioperative Care, School of Medicine, University of California Irvine, Irvine, California 92697, USA.
Neurotherapeutics. 2009 Oct;6(4):679-92.
Abstract
Voltage-gated calcium channels (VGCC) play obligatory roles in diverse physiological functions. Pathological conditions leading to changes in their biophysical properties and expression levels may cause malfunctions of VGCC-mediated activities, resulting in disease states. It is believed that changes in VGCC properties under pain-inducing conditions may play a causal role in the development of chronic pain, including nerve injury-induced pain or neuropathic pain. For the past several decades, preclinical and clinical research in developing VGCC blockers or modulators for chronic pain management has been fruitful, leading to some U.S. Food and Drug Administration-approved drugs currently available for chronic pain management. However, their efficacy in pain relief is limited in some patients, and their long-term use is limited by their side-effect profiles. Certainly, there is room for improvement in developing more subtype-specific VGCC blockers or modulators for chronic pain conditions. In this review, we summarized the most recent preclinical and clinical studies related to chronic pain medications acting on the VGCC. We also included clinical trials aiming to expand the application of approved VGCC drugs to different pain states derived from various pathological conditions, as well as drug combination therapies trying to improve the efficacies and side-effect profiles of current pain medications.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755636/pdf/nihms133252.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
