title: The role of microglia in the pathobiology of neuropathic pain development: what do we know?
abstract: Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after nerve injury and are involved in the activation of microglial cells. These activated cells in turn release factors that increase the excitation and decrease the inhibition of interneurons. Microglial cells release factors such as interleukin (IL)-6, IL-1β and tumour necrosis factor-α (TNF-α) that cause the painful symptoms. It is becoming increasingly apparent that an intricate network of cytokines and cellular signalling mechanisms underpin the complex relationship between microglia and various cell types including neurones, astrocytes, oligodendrocytes, mast cells and T-cells. Although the precise mechanism of action of microglial cells in producing neuropathic pain has not been completely elucidated, research into these different activating factors and cytokines is providing further insight into the role of microglial cells in the development and maintenance of neuropathic pain. Further studies also are required to elucidate how "pain" mediators act on neurones and how the interactions between these mediators, or between neurones and glia in the presence of these mediators occur, in order to develop effective therapies for the management of neuropathic pain.
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Alam
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.|Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: A Eusman
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pal
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D006801:Humans; D006930:Hyperalgesia; D017628:Microglia / Q000473:pathology*; D009437:Neuralgia / Q000473:pathology* / Q000628:therapy
keywords: astrocytes; cytokines; microglia; neuropathic pain