Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior
<p>Abstract</p> <p>Background</p> <p>Transient receptor potential vanilloid 1 (TRPV1) channels are important membrane sensors on peripheral nerve endings and on supportive non-neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with activation of calciu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2010-08-01
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| Series: | Molecular Pain |
| Online Access: | http://www.molecularpain.com/content/6/1/46 |
| _version_ | 1818154186789879808 |
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| author | Lu Ying Kochukov Mikhail Y Westlund Karin N McNearney Terry A |
| author_facet | Lu Ying Kochukov Mikhail Y Westlund Karin N McNearney Terry A |
| author_sort | Lu Ying |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Transient receptor potential vanilloid 1 (TRPV1) channels are important membrane sensors on peripheral nerve endings and on supportive non-neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with activation of calcium and sodium fluxes to pH, thermal, chemical, osmotic, mechanical and other stimuli abundant in inflamed joints. In the present study, the kaolin/carrageenan (k/c) induced knee joint arthritis model in rats, as well as primary and clonal human synoviocyte cultures were used to understand the reciprocal interactions between reactive nitroxidative species (ROS) and functional TRPV1 channels. ROS generation was monitored with ROS sensitive dyes using live cell imaging <it>in vitro </it>and in spinal tissue histology, as well as with measurement of ROS metabolites in culture media using HPLC.</p> <p>Results</p> <p>Functional responses in the experimental arthritis model, including increased nociceptive responses (thermal and mechanical hyperalgesia and allodynia), knee joint temperature reflecting local blood flow, and spinal cord ROS elevations were reduced by the ROS scavenger PBN after intraperitoneal pretreatment. Increases in TRPV1 and ROS, generated by synoviocytes <it>in vitro</it>, were reciprocally blocked by TRPV1 antagonists and the ROS scavenger. Further evidence is presented that synoviocyte responses to ROS and TRPV1 activation include increases in TNFα and COX-2, both measured as an indicator of the inflammation <it>in vitro</it>.</p> <p>Conclusions</p> <p>The results demonstrate that contributions of ROS to pronociceptive responses and neurogenic inflammation are mediated both centrally and peripherally. Responses are mediated by TRPV1 locally in the knee joint by synoviocytes, as well as by ROS-induced sensitization in the spinal cord. These findings and those of others reported in the literature indicate reciprocal interactions between TRPV1 and ROS play critical roles in the pathological and nociceptive responses active during arthritic inflammation.</p> |
| first_indexed | 2024-12-11T14:22:31Z |
| format | Article |
| id | doaj.art-fd9a2989f5c6439b8f2947937b45e297 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-12-11T14:22:31Z |
| publishDate | 2010-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-fd9a2989f5c6439b8f2947937b45e2972022-12-22T01:02:51ZengSAGE PublishingMolecular Pain1744-80692010-08-01614610.1186/1744-8069-6-46Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behaviorLu YingKochukov Mikhail YWestlund Karin NMcNearney Terry A<p>Abstract</p> <p>Background</p> <p>Transient receptor potential vanilloid 1 (TRPV1) channels are important membrane sensors on peripheral nerve endings and on supportive non-neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with activation of calcium and sodium fluxes to pH, thermal, chemical, osmotic, mechanical and other stimuli abundant in inflamed joints. In the present study, the kaolin/carrageenan (k/c) induced knee joint arthritis model in rats, as well as primary and clonal human synoviocyte cultures were used to understand the reciprocal interactions between reactive nitroxidative species (ROS) and functional TRPV1 channels. ROS generation was monitored with ROS sensitive dyes using live cell imaging <it>in vitro </it>and in spinal tissue histology, as well as with measurement of ROS metabolites in culture media using HPLC.</p> <p>Results</p> <p>Functional responses in the experimental arthritis model, including increased nociceptive responses (thermal and mechanical hyperalgesia and allodynia), knee joint temperature reflecting local blood flow, and spinal cord ROS elevations were reduced by the ROS scavenger PBN after intraperitoneal pretreatment. Increases in TRPV1 and ROS, generated by synoviocytes <it>in vitro</it>, were reciprocally blocked by TRPV1 antagonists and the ROS scavenger. Further evidence is presented that synoviocyte responses to ROS and TRPV1 activation include increases in TNFα and COX-2, both measured as an indicator of the inflammation <it>in vitro</it>.</p> <p>Conclusions</p> <p>The results demonstrate that contributions of ROS to pronociceptive responses and neurogenic inflammation are mediated both centrally and peripherally. Responses are mediated by TRPV1 locally in the knee joint by synoviocytes, as well as by ROS-induced sensitization in the spinal cord. These findings and those of others reported in the literature indicate reciprocal interactions between TRPV1 and ROS play critical roles in the pathological and nociceptive responses active during arthritic inflammation.</p>http://www.molecularpain.com/content/6/1/46 |
| spellingShingle | Lu Ying Kochukov Mikhail Y Westlund Karin N McNearney Terry A Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior Molecular Pain |
| title | Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior |
| title_full | Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior |
| title_fullStr | Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior |
| title_full_unstemmed | Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior |
| title_short | Impact of central and peripheral TRPV1 and ROS levels on proinflammatory mediators and nociceptive behavior |
| title_sort | impact of central and peripheral trpv1 and ros levels on proinflammatory mediators and nociceptive behavior |
| url | http://www.molecularpain.com/content/6/1/46 |
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