The role of CXCL7 in peripheral nerve injury-induced neuropathic pain
碩士 === 國立臺灣大學 === 藥理學研究所 === 105 === Neuropathic pain is a problem in general population because of the complexity of neuropathic symptoms, poor outcomes and difficult treatment decision. Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system and can be subtype...
Main Authors: | , |
---|---|
Other Authors: | |
Format: | Others |
Language: | en_US |
Published: |
2017
|
Online Access: | http://ndltd.ncl.edu.tw/handle/4z4g6p |
id |
ndltd-TW-105NTU05550004 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TW-105NTU055500042019-05-15T23:39:37Z http://ndltd.ncl.edu.tw/handle/4z4g6p The role of CXCL7 in peripheral nerve injury-induced neuropathic pain 趨化因子CXCL7在周邊神經損傷引起神經病變性疼痛之探討 Wen Lee 李雯 碩士 國立臺灣大學 藥理學研究所 105 Neuropathic pain is a problem in general population because of the complexity of neuropathic symptoms, poor outcomes and difficult treatment decision. Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system and can be subtyped as central and peripheral neuropathic pain. Until now, conventional pharmacological treatments for neuropathic pain are effective in <50% of patients. Therefore, clarifying actual mechanism in neuropathic pain and finding a new target remain important parts for developing new drugs. Neuroinflammation has been reported to be involved in the pathophysiology of neuropathic pain and is an emerging target of treatment. Although the cytokine/chemokine pathways play a major role in neuroinflammation, the exact mechanism in neuropathic pain remains unclear. To investigate the cytokines/chemokines changes, we used neuropathic pain animal model produced by unilateral L5 spinal nerve ligation-and-cut (SNL) and electronic von Frey test and plantar test for pain assessment (including mechanical and thermal hyperalgesia, respectively). We then screened cytokine expression in the cerebrospinal fluid using cytokine array, and it was found that CXCL7 increased markedly in SNL rats compared with control. The expression levels of both protein and messenger RNA of CXCL7 were up-regulated in spinal cord dorsal horn samples of SNL rats compared with control.Furthermore, intrathecal administration of recombinant chemokine CXCL7 induced mechanical and thermal hyperalgesia and increased glia activation and sensory neuropeptide CGRP expression level. To investigate the involvement of CXCR1/CXCR2, receptors of CXCL7, a CXCR1/CXCR2 antagonist reparixin-L-lysine salt (reparixin) was co-administered intrathecally with CXCL7 via osmotic pump. It was found that CXCR1/CXCR2 antagonist reversed CXCL7-induced hyperalgesia. We also evaluated the effect of CXCR1/CXCR2 in SNL rats. Right after SNL, intrathecal infusion of CXCR1/CXCR2 antagonist reparixin via osmotic pump for 7 days attenuated SNL-induced hyperalgesia and glia activation. These results indicate that CXCL7 might be involved in neuropathic pain and CXCR1/CXCR2 antagonist might be developed as drug for the treatment of neuropathic pain. Wen-Mei Fu 符文美 2017 學位論文 ; thesis 60 en_US |
collection |
NDLTD |
language |
en_US |
format |
Others
|
sources |
NDLTD |
description |
碩士 === 國立臺灣大學 === 藥理學研究所 === 105 === Neuropathic pain is a problem in general population because of the complexity of neuropathic symptoms, poor outcomes and difficult treatment decision. Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system and can be subtyped as central and peripheral neuropathic pain. Until now, conventional pharmacological treatments for neuropathic pain are effective in <50% of patients. Therefore, clarifying actual mechanism in neuropathic pain and finding a new target remain important parts for developing new drugs. Neuroinflammation has been reported to be involved in the pathophysiology of neuropathic pain and is an emerging target of treatment. Although the cytokine/chemokine pathways play a major role in neuroinflammation, the exact mechanism in neuropathic pain remains unclear. To investigate the cytokines/chemokines changes, we used neuropathic pain animal model produced by unilateral L5 spinal nerve ligation-and-cut (SNL) and electronic von Frey test and plantar test for pain assessment (including
mechanical and thermal hyperalgesia, respectively). We then screened cytokine expression in the cerebrospinal fluid using cytokine array, and it was found that CXCL7 increased markedly in SNL rats compared with control. The expression levels of both protein and messenger RNA of CXCL7 were up-regulated in spinal cord dorsal horn samples of SNL rats compared with control.Furthermore, intrathecal administration of recombinant chemokine CXCL7 induced mechanical and thermal hyperalgesia and increased glia activation and sensory neuropeptide CGRP expression level. To investigate the involvement of CXCR1/CXCR2, receptors of CXCL7, a CXCR1/CXCR2 antagonist reparixin-L-lysine salt (reparixin) was co-administered intrathecally with CXCL7 via osmotic pump. It was found that CXCR1/CXCR2 antagonist reversed CXCL7-induced hyperalgesia. We also evaluated the effect of CXCR1/CXCR2 in SNL rats. Right after SNL, intrathecal infusion of
CXCR1/CXCR2 antagonist reparixin via osmotic pump for 7 days attenuated SNL-induced hyperalgesia and glia activation. These results indicate that CXCL7 might be involved in neuropathic pain and CXCR1/CXCR2 antagonist might be developed as drug for the treatment of neuropathic pain.
|
author2 |
Wen-Mei Fu |
author_facet |
Wen-Mei Fu Wen Lee 李雯 |
author |
Wen Lee 李雯 |
spellingShingle |
Wen Lee 李雯 The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
author_sort |
Wen Lee |
title |
The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
title_short |
The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
title_full |
The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
title_fullStr |
The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
title_full_unstemmed |
The role of CXCL7 in peripheral nerve injury-induced neuropathic pain |
title_sort |
role of cxcl7 in peripheral nerve injury-induced neuropathic pain |
publishDate |
2017 |
url |
http://ndltd.ncl.edu.tw/handle/4z4g6p |
work_keys_str_mv |
AT wenlee theroleofcxcl7inperipheralnerveinjuryinducedneuropathicpain AT lǐwén theroleofcxcl7inperipheralnerveinjuryinducedneuropathicpain AT wenlee qūhuàyīnzicxcl7zàizhōubiānshénjīngsǔnshāngyǐnqǐshénjīngbìngbiànxìngténgtòngzhītàntǎo AT lǐwén qūhuàyīnzicxcl7zàizhōubiānshénjīngsǔnshāngyǐnqǐshénjīngbìngbiànxìngténgtòngzhītàntǎo AT wenlee roleofcxcl7inperipheralnerveinjuryinducedneuropathicpain AT lǐwén roleofcxcl7inperipheralnerveinjuryinducedneuropathicpain |
_version_ |
1719151318620176384 |