Pharmacology & therapeutics
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Review
The function of microglia through purinergic receptors: neuropathic pain and cytokine release.
Microglia play an important role as immune cells in the central nervous system (CNS). Microglia are activated in threatened physiological homeostasis, including CNS trauma, apoptosis, ischemia, inflammation, and infection. Activated microglia show a stereotypic, progressive series of changes in morphology, gene expression, function, and number and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and can also act on neurons to alter their function. ⋯ ATP is able to activate MAPK, leading to the release of bioactive substances, including cytokines, from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain. Understanding the key roles of ATP receptors, including P2X4 receptors, in the microglia may lead to new strategies for the management of neuropathic pain.
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Many known painkillers are not always effective in the therapy of chronic neuropathic pain manifested by hyperalgesia and tactile allodynia. The mechanisms underlying neuropathic pain appear to be complicated and to differ from acute and inflammatory pain. Recent advances in pain research provide us with a clear picture for the molecular mechanisms of acute pain, and substantial information is available concerning the plasticity that occurs under conditions of neuropathic pain. ⋯ The current study using lysophosphatidic acid (LPA) receptor knockout mice revealed that LPA produced by nerve injury initiates neuropathic pain and demyelination following partial sciatic nerve ligation (PSNL). A single injection of LPA was found to mimic PSNL in terms of neuropathic pain and its underlying mechanisms. This discovery may lead to the subsequent discovery of LPA-induced secondary genes, which would be therapeutic targets for neuropathic pain.