Warmth suppresses and desensitizes damage-sensing ion channel TRPA1
<p>Abstract</p> <p>Background</p> <p>Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-03-01
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| Series: | Molecular Pain |
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| Online Access: | http://www.molecularpain.com/content/8/1/22 |
| _version_ | 1828833065094348800 |
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| author | Wang Sen Lee Jongseok Ro Jin Y Chung Man-Kyo |
| author_facet | Wang Sen Lee Jongseok Ro Jin Y Chung Man-Kyo |
| author_sort | Wang Sen |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons.</p> <p>Results</p> <p>Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury.</p> <p>Conclusion</p> <p>These results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach.</p> |
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| format | Article |
| id | doaj.art-8321cc119fab4e6080669d84f0829466 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-12-12T17:07:41Z |
| publishDate | 2012-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-8321cc119fab4e6080669d84f08294662022-12-22T00:17:55ZengSAGE PublishingMolecular Pain1744-80692012-03-01812210.1186/1744-8069-8-22Warmth suppresses and desensitizes damage-sensing ion channel TRPA1Wang SenLee JongseokRo Jin YChung Man-Kyo<p>Abstract</p> <p>Background</p> <p>Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons.</p> <p>Results</p> <p>Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury.</p> <p>Conclusion</p> <p>These results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach.</p>http://www.molecularpain.com/content/8/1/22TRPA1PainTemperature |
| spellingShingle | Wang Sen Lee Jongseok Ro Jin Y Chung Man-Kyo Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 Molecular Pain TRPA1 Pain Temperature |
| title | Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 |
| title_full | Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 |
| title_fullStr | Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 |
| title_full_unstemmed | Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 |
| title_short | Warmth suppresses and desensitizes damage-sensing ion channel TRPA1 |
| title_sort | warmth suppresses and desensitizes damage sensing ion channel trpa1 |
| topic | TRPA1 Pain Temperature |
| url | http://www.molecularpain.com/content/8/1/22 |
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