Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury
<p>Abstract</p> <p>Background</p> <p>Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-02-01
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| Series: | Molecular Pain |
| Subjects: | |
| Online Access: | http://www.molecularpain.com/content/8/1/8 |
| _version_ | 1811244747680907264 |
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| author | Okubo Masamichi Yamanaka Hiroki Kobayashi Kimiko Kanda Hirosato Dai Yi Noguchi Koichi |
| author_facet | Okubo Masamichi Yamanaka Hiroki Kobayashi Kimiko Kanda Hirosato Dai Yi Noguchi Koichi |
| author_sort | Okubo Masamichi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown.</p> <p>Methods</p> <p>Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double-labeling analysis of <it>in situ </it>hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086).</p> <p>Results</p> <p>RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia.</p> <p>Conclusions</p> <p>Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.</p> |
| first_indexed | 2024-04-12T14:30:24Z |
| format | Article |
| id | doaj.art-6172bb039e3a470da2b1c9fad3a1f58e |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-12T14:30:24Z |
| publishDate | 2012-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-6172bb039e3a470da2b1c9fad3a1f58e2022-12-22T03:29:17ZengSAGE PublishingMolecular Pain1744-80692012-02-0181810.1186/1744-8069-8-8Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injuryOkubo MasamichiYamanaka HirokiKobayashi KimikoKanda HirosatoDai YiNoguchi Koichi<p>Abstract</p> <p>Background</p> <p>Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown.</p> <p>Methods</p> <p>Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double-labeling analysis of <it>in situ </it>hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086).</p> <p>Results</p> <p>RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia.</p> <p>Conclusions</p> <p>Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.</p>http://www.molecularpain.com/content/8/1/8PAFSynthaseReceptorMicrogliaNeuronNeuropathic pain |
| spellingShingle | Okubo Masamichi Yamanaka Hiroki Kobayashi Kimiko Kanda Hirosato Dai Yi Noguchi Koichi Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury Molecular Pain PAF Synthase Receptor Microglia Neuron Neuropathic pain |
| title | Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| title_full | Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| title_fullStr | Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| title_full_unstemmed | Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| title_short | Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| title_sort | up regulation of platelet activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury |
| topic | PAF Synthase Receptor Microglia Neuron Neuropathic pain |
| url | http://www.molecularpain.com/content/8/1/8 |
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