A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells

Correa, Fernando; Docagne, Fabián; Mestre, Leyre; Clemente, Diego; Hernangómez, Miriam; Loría, Frida; Guaza, Carmen

doi:10.1016/j.bcp.2008.09.014

Cited by 86 publications

(72 citation statements)

References 52 publications

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“…Navarrete and coworkers have recently shown that NADA is a potent inhibitor of prostaglandin E2 (PGE2) synthesis and of free radical formation in primary lipopolysaccharide (LPS) stimulated microglial cells [107]. Consistently, anandamide is capable of enhancing the anti-inflammatory cytokine interleukin 10 (IL-10) and regulating other cytokine production such as IL-12 and IL-23 in activated microglia by targeting CB(2) receptors [108,109].…”

Section: +mentioning

confidence: 88%

Role of Endocannabinoids in Neuron-Glial Crosstalk

Luongo¹,

Palazzo²,

Novellis³

et al. 2010

TOPAINJ

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Evidence shows bidirectional crosstalk between neurons and glia, suggesting that glia play an active role in synaptic plasticity leading to chronic pain. Importantly, gliosis has been implicated in the development and maintenance of hyperalgesia or allodynia following chronic inflammation or nerve injury. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG), or the lipoamino acid N-arachydonoyldopamine (NADA), are fatty acid derivative neurotransmitters, named endocannabinoids (eCBs). These perform several biological actions, via the activation of cannabinoid type 1 and 2 (CB1/CB2) receptors belonging to the G-protein-coupled receptor family. The eCBs are produced on demand by neurons or glial cells and it has been suggested that they might be involved in the crosstalk between astrocytes, microglia, oligodendrocytes and neurons. In chronic pain, the modified glial or neural activity also seems to be associated with changes in eCB levels in pain processing areas either in the spinal cord or the brain. The activation of the eCB system in microglia or astrocytes could be crucial in modulating axonal growth and synaptogenesis at the base of neural phenotypic changes. Furthermore, changes in eCBs levels have been suggested to affect the destiny of cells: death or survival may depend on a specific pain condition. Thus, although eCBs are emerging as neurotransmitters responsible for the regulation of glia-neuron crosstalk in chronic pain, the precise mechanisms leading to eCB production, the origin and the timecourse of eCB release, the eCB release switch from one cell type to the other and their movement or catabolism across the glial or neural cell membrane nevertheless still remain unknown. These issues together with alternative eCB targets will be addressed in the current review.

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Section: +mentioning

confidence: 88%

Role of Endocannabinoids in Neuron-Glial Crosstalk

Luongo¹,

Palazzo²,

Novellis³

et al. 2010

TOPAINJ

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“…Conversely, overexpression of CB 2 receptors protected against nerve injury-induced thermal and mechanical allodynia and prevented glial activation in the spinal cord. Numerous other studies have also implicated EC signalling in glial cell activation (64,103,104) .…”

Section: Spinal Mechanismsmentioning

confidence: 98%

Endocannabinoid system and pain: an introduction

Burston

Woodhams

2013

Proc. Nutr. Soc.

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The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states. Pain: Endocannabinoid: AnalgesiaFrom an evolutionary standpoint, pain can be considered a necessary evil, providing a potent warning system to protect an individual from present and future harm. However, not all pain is part of this adaptive response, e.g. persistent pain after injury healing (chronic pain) or pain arising from damage to nerve tissue (neuropathic pain). Pain is the most common complaint in those seeking a physician, and a recent study suggests that pain represents the greatest economic burden of any pathological condition in the USA, with an estimated annual cost of $565-635 billion (1) . Many chronic pain states are refractory to standard analgesics, and even in those which do respond, pain control can be incomplete or only short-term in nature. Of the imperfect currently available analgesics, the most efficacious are the opioids which exploit an endogenous pain control pathway within the central nervous system. However, opioids have significant issues with tolerance, dependence, respiratory depression and opioid-induced hyperalgesia (2) . Over the past few decades, the existence of a second endogenous anti-nociceptive pathway has been revealed: the endocannabinoid (EC) system. *Corresponding author: J. J. Burston, fax +44 (0)115 823 0142, email james.burston@nottingham.ac.uk Abbreviations: 2-AG, 2-arachidonoylglycerol; ACC, anterior cingulate cortex; AEA, anandamide; CB 1 , cannab...

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“…In vitro studies suggest that endocannabinoids elicit anti-inflammatory effects comparable to those of exogenous cannabinoids. Increasing AEA tone, either directly or via inhibition of its degradation or uptake, has been demonstrated to reduce the levels of proinflammatory cytokines and inflammatory mediators such as TNFα, IL-1β and nitric oxide, and enhance the release of the anti-inflammatory cytokine IL-10 in vitro (Puffenbarger et al, 2000;Chang et al, 2001;Facchinetti et al, 2003;Ortega-Gutierrez et al, 2005;Tham et al, 2007;Correa et al, 2009;Correa et al, 2010). However, AEA has also been demonstrated to enhance IL-6 in astrocyte cultures (Molina-Holgado et al, 1998;Ortega-Gutierrez et al, 2005).…”

Section: Introductionmentioning

confidence: 98%