Receptores purinérgicos y dolor / Pain and purinergic receptors

Octubre 28, 2017. No. 2895

Señalización purinérgica en microglia en la patogenia del dolor neuropático. Purinergic signaling in microglia in the pathogenesis of neuropathic pain. Inoue K1. Author information Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(4):174-182. doi: 10.2183/pjab.93.011. Abstract Nerve injury often causes debilitating chronic pain, referred to as neuropathic pain, which is refractory to currently available analgesics including morphine. Many reports indicate that activated spinal microglia evoke neuropathic pain. The P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in spinal microglia after nerve injury by several factors, including CC chemokine receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord, interferon regulatory factor 8 (IRF8) and IRF5. Inhibition of P2X4R function suppresses neuropathic pain, indicating that microglial P2X4R play a key role in evoking neuropathic pain. PDF Microglia en la médula espinal y dolor neuropático Microglia in the spinal cord and neuropathic pain. Tsuda M1. Author information J Diabetes Investig. 2016 Jan;7(1):17-26. doi: 10.1111/jdi.12379. Epub 2015 Jun 23. Abstract In contrast to physiological pain, pathological pain is not dependent on the presence of tissue-damaging stimuli. One type of pathological pain- neuropathic pain - is often a consequence of nerve injury or of diseases such as diabetes. Neuropathic pain can be agonizing, can persist over long periods and is often resistant to known painkillers. A growing body of evidence shows that many pathological processes within the central nervous system are mediated by complex interactions between neurons and glial cells. In the case of painful peripheral neuropathy, spinal microglia react and undergo a series of changes that directly influence the establishment of neuropathic pain states. After nerve damage, purinergic P2X4 receptors (non-selective cation channels activated by extracellular adenosine triphosphate) are upregulated in spinal microglia in a manner that depends on the transcription factors interferon regulatory factor 8 and 5, both of which are expressed in microglia after peripheral nerve injury. P2X4 receptor expression on the cell surface of microglia is also regulated at the post-translational level by signaling from CC chemokine receptor chemotactic cytokine receptor 2. Furthermore, spinal microglia in response to extracellular stimuli results in signal transduction through intracellular signaling cascades, such as mitogen-activated protein kinases, p38 and extracellular signal-regulated protein kinase. Importantly, inhibiting the function or expression of these microglial molecules suppresses the aberrant excitability of dorsal horn neurons and neuropathic pain. These findings show that spinal microglia are a central player in mechanisms for neuropathic pain, and might be a potential target for treating the chronic pain state. KEYWORDS: Microglia; Painful diabetic neuropathy; Purinergic receptors PDF Identificación de agonistas de receptor A3 como nuevos analgésicos no narcóticos Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics. Janes K1, Symons-Liguori AM1, Jacobson KA2, Salvemini D1. Author information Br J Pharmacol. 2016 Apr;173(8):1253-67. doi: 10.1111/bph.13446. Epub 2016 Mar 6. Abstract Chronic pain negatively impacts the quality of life in a variety of patient populations. The current therapeutic repertoire is inadequate in managing patient pain and warrants the development of new therapeutics. Adenosine and its four cognate receptors (A1 , A2A , A2B and A3 ) have important roles in physiological and pathophysiological states, including chronic pain. Preclinical and clinical studies have revealed that while adenosine and agonists of the A1 and A2A receptors have antinociceptive properties, their therapeutic utility is limited by adverse cardiovascular side effects. In contrast, our understanding of the A3 receptor is only in its infancy, but exciting preclinical observations of A3 receptor antinociception, which have been bolstered by clinical trials of A3 receptor agonists in other disease states, suggest pain relief without cardiovascular side effects and with sufficient tolerability. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and to consider the current data regarding A3 receptor-mediated antinociception. We will highlight recent findings regarding the impact of the A3 receptor on pain pathways and examine the current state of selective A3 receptor agonists used for these studies. The adenosine-to-A3 receptor pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief from chronic pain. PDF XXVII Congreso Peruano de Anestesiología Lima, Noviembre 2-4, 2017 Informes / Informataion LI Congreso Mexicano de Anestesiología Mérida Yucatán, Noviembre 21-25, 2017 Información / Information

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org