Abstract
Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Botulinum Toxins / pharmacology
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Immunohistochemistry
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Injections, Spinal
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Lysophospholipids / metabolism
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Lysophospholipids / pharmacology
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Lysophospholipids / physiology
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Male
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Mice
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Mice, Knockout
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Nerve Fibers, Unmyelinated / drug effects
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Nerve Fibers, Unmyelinated / metabolism
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Nerve Fibers, Unmyelinated / physiology*
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Neuralgia / etiology
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Neuralgia / physiopathology*
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Peripheral Nervous System / drug effects
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Peripheral Nervous System / injuries
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Peripheral Nervous System / physiopathology
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Posterior Horn Cells / drug effects
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Posterior Horn Cells / metabolism
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / physiology*
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Sciatic Nerve / drug effects
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Sciatic Nerve / injuries
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Sciatic Nerve / physiopathology
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Spinal Cord / metabolism
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Substance P / metabolism*
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Substance P / pharmacology
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Substance P / physiology
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rhoA GTP-Binding Protein / antagonists & inhibitors
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rhoA GTP-Binding Protein / metabolism
Substances
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Lysophospholipids
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Receptors, Lysophosphatidic Acid
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Substance P
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Botulinum Toxins
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rhoA GTP-Binding Protein