Blog
About

84
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Different immune cells mediate mechanical pain hypersensitivity in male and female mice.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, we found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research.

          Related collections

          Most cited references 24

          • Record: found
          • Abstract: not found
          • Article: not found

          Quantitative assessment of tactile allodynia in the rat paw

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

            Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling. Copyright © 2013 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain.

              Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain.
                Bookmark

                Author and article information

                Affiliations
                [1 ] 1] Department of Psychology, McGill University, Montreal, Quebec, Canada. [2] Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
                [2 ] 1] Department of Psychology, McGill University, Montreal, Quebec, Canada. [2] Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada. [3] Department of Physiology, University of Toronto, Toronto, Ontario, Canada. [4] University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada.
                [3 ] Department of Psychology, McGill University, Montreal, Quebec, Canada.
                [4 ] 1] Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada. [3] University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada.
                [5 ] Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
                [6 ] Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
                [7 ] Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
                [8 ] Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
                [9 ] 1] Faculty of Dentistry, McGill University, Montreal, Quebec, Canada. [2] Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
                [10 ] 1] Department of Psychology, McGill University, Montreal, Quebec, Canada. [2] Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
                Journal
                Nat. Neurosci.
                Nature neuroscience
                1546-1726
                1097-6256
                Aug 2015
                : 18
                : 8
                nn.4053 10.1038/nn.4053 26120961 4772157 NIHMS762591

                Comments

                Comment on this article