Top

Published in:

Open Access 01-12-2006 | Short report

Loss of spinal substance P pain transmission under the condition of LPA₁ receptor-mediated neuropathic pain

Authors: Makoto Inoue, Asuka Yamaguchi, Megumi Kawakami, Jerold Chun, Hiroshi Ueda

Published in: Molecular Pain | Issue 1/2006

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.

Available only for authorised users

Dubner R: Neuronal plasticity in the spinal cord medullary dorsal horn: a possible role in central pain mechanisms. In: Pain and central nervous system disease (Casey KL ed), Raven Press New York 1991, 143–155.

Woolf CJ, Shortland P, Coggeshall RE: Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992,355(6355):75–78. 10.1038/355075a0PubMedCrossRef

Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999,353(9168):1959–1964. 10.1016/S0140-6736(99)01307-0PubMedCrossRef

Doubell TP, R.J. M, C.J. W: The dorsal horn: state-dependent sensory processing, plasticity and the generation of pain. In: Textbook of Pain Fourth Edition PD Wall and R Melzack (Eds), Churchill Livingstone London 1999, 165–181.

Woolf CJ, Salter MW: Neuronal plasticity: increasing the gain in pain. Science 2000,288(5472):1765–1769. 10.1126/science.288.5472.1765PubMedCrossRef

Ueda H: Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther 2006,109(1–2):57–77. 10.1016/j.pharmthera.2005.06.003PubMedCrossRef

Ueda H, Rashid MH: Molecular mechanism of neuropathic pain. Drug News Perspect 2003,16(9):605–613. 10.1358/dnp.2003.16.9.829343PubMedCrossRef

Castro-Lopes JM, Coimbra A, Grant G, Arvidsson J: Ultrastructural changes of the central scalloped (C1) primary afferent endings of synaptic glomeruli in the substantia gelatinosa Rolandi of the rat after peripheral neurotomy. J Neurocytol 1990,19(3):329–337. 10.1007/BF01188402PubMedCrossRef

Eichholtz T, Jalink K, Fahrenfort I, Moolenaar WH: The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J 1993, 291 ( Pt 3): 677–680.

10.

Fukushima N, Ishii I, Contos JJ, Weiner JA, Chun J: Lysophospholipid receptors. Annu Rev Pharmacol Toxicol 2001, 41: 507–534. 10.1146/annurev.pharmtox.41.1.507PubMedCrossRef

11.

Fukushima N, Ye X, Chun J: Neurobiology of lysophosphatidic acid signaling. Neuroscientist 2002,8(6):540–550. 10.1177/1073858402238513PubMedCrossRef

12.

Ishii I, Fukushima N, Ye X, Chun J: Lysophospholipid receptors: signaling and biology. Annu Rev Biochem 2004, 73: 321–354. 10.1146/annurev.biochem.73.011303.073731PubMedCrossRef

13.

Kranenburg O, Poland M, van Horck FP, Drechsel D, Hall A, Moolenaar WH: Activation of RhoA by lysophosphatidic acid and Galpha12/13 subunits in neuronal cells: induction of neurite retraction. Mol Biol Cell 1999,10(6):1851–1857.PubMedCentralPubMedCrossRef

14.

Chun J, Rosen H: Lysophospholipid receptors as potential drug targets in tissue transplantation and autoimmune diseases. Curr Pharm Des 2006,12(2):161–171. 10.2174/138161206775193109PubMedCrossRef

15.

Gardell SE, Dubin AE, Chun J: Emerging medicinal roles for lysophospholipid signaling. Trends Mol Med 2006,12(2):65–75. 10.1016/j.molmed.2005.12.001PubMedCrossRef

16.

Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H: Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med 2004,10(7):712–718. 10.1038/nm1060PubMedCrossRef

17.

Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983,16(2):109–110. 10.1016/0304-3959(83)90201-4PubMedCrossRef

18.

Rashid MH, Inoue M, Kondo S, Kawashima T, Bakoshi S, Ueda H: Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain. J Pharmacol Exp Ther 2003,304(3):940–948. 10.1124/jpet.102.046250PubMedCrossRef

19.

Inoue M, Rashid MH, Kawashima T, Matsumoto M, Maeda T, Kishioka S, Ueda H: The algogenic-induced nociceptive flexion test in mice: studies on sensitivity of the test and stress on animals. Brain Res Bull 2003,60(3):275–281. 10.1016/S0361-9230(03)00045-5PubMedCrossRef

20.

Malmberg AB, Basbaum AI: Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain 1998,76(1–2):215–222. 10.1016/S0304-3959(98)00045-1PubMedCrossRef

21.

Rashid MH, Inoue M, Matsumoto M, Ueda H: Switching of bradykinin-mediated nociception following partial sciatic nerve injury in mice. J Pharmacol Exp Ther 2004,308(3):1158–1164. 10.1124/jpet.103.060335PubMedCrossRef

22.

Renback K, Inoue M, Ueda H: Lysophosphatidic acid-induced, pertussis toxin-sensitive nociception through a substance P release from peripheral nerve endings in mice. Neurosci Lett 1999,270(1):59–61. 10.1016/S0304-3940(99)00464-4PubMedCrossRef

23.

Renback K, Inoue M, Yoshida A, Nyberg F, Ueda H: Vzg-1/lysophosphatidic acid-receptor involved in peripheral pain transmission. Brain Res Mol Brain Res 2000,75(2):350–354. 10.1016/S0169-328X(99)00333-2PubMedCrossRef

Title: Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain
Authors: Makoto Inoue
Asuka Yamaguchi
Megumi Kawakami
Jerold Chun
Hiroshi Ueda
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2006
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-2-25

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Loss of spinal substance P pain transmission under the condition of LPA₁ receptor-mediated neuropathic pain

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2006

Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK)

Breaking down the barriers: fMRI applications in pain, analgesia and analgesics

Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia

Nav 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin