New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View
One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2011-12-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1424-8247/5/1/16/ |
| _version_ | 1819073198385266688 |
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| author | Antonio Ferrer-Montiel José Manuel González-Ros Isabel Devesa Asia Fernández-Carvajal Gregorio Fernández-Ballester |
| author_facet | Antonio Ferrer-Montiel José Manuel González-Ros Isabel Devesa Asia Fernández-Carvajal Gregorio Fernández-Ballester |
| author_sort | Antonio Ferrer-Montiel |
| collection | DOAJ |
| description | One approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known as nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have validated these channels as therapeutic targets for pain intervention. Several thermoTRP modulators have progressed towards clinical development, although most failed because of the appearance of unpredicted side effects. Thus, there is yet a need to develop novel channel modulators with improved therapeutic index. Here, we review the current state-of-the art and illustrate new pharmacological paradigms based on TRPV1 that include: (i) the identification of activity-dependent modulators of this thermoTRP channel; (ii) the design of allosteric modulators that interfere with protein-protein interaction involved in the functional coupling of stimulus sensing and gate opening; and (iii) the development of compounds that abrogate the inflammation-mediated increase of receptor expression in the neuronal surface. These new sites of action represent novel strategies to modulate pathologically active TRPV1, while minimizing an effect on the TRPV1 subpopulation involved in physiological and protective roles, thus increasing their potential therapeutic use. |
| first_indexed | 2024-12-21T17:49:48Z |
| format | Article |
| id | doaj.art-72d1de75920345358e2851c4ae56fade |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-21T17:49:48Z |
| publishDate | 2011-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-72d1de75920345358e2851c4ae56fade2022-12-21T18:55:23ZengMDPI AGPharmaceuticals1424-82472011-12-0151164810.3390/ph5010016New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of ViewAntonio Ferrer-MontielJosé Manuel González-RosIsabel DevesaAsia Fernández-CarvajalGregorio Fernández-BallesterOne approach to develop successful pain therapies is the modulation of dysfunctional ion channels that contribute to the detection of thermal, mechanical and chemical painful stimuli. These ion channels, known as thermoTRPs, promote the sensitization and activation of primary sensory neurons known as nociceptors. Pharmacological blockade and genetic deletion of thermoTRP have validated these channels as therapeutic targets for pain intervention. Several thermoTRP modulators have progressed towards clinical development, although most failed because of the appearance of unpredicted side effects. Thus, there is yet a need to develop novel channel modulators with improved therapeutic index. Here, we review the current state-of-the art and illustrate new pharmacological paradigms based on TRPV1 that include: (i) the identification of activity-dependent modulators of this thermoTRP channel; (ii) the design of allosteric modulators that interfere with protein-protein interaction involved in the functional coupling of stimulus sensing and gate opening; and (iii) the development of compounds that abrogate the inflammation-mediated increase of receptor expression in the neuronal surface. These new sites of action represent novel strategies to modulate pathologically active TRPV1, while minimizing an effect on the TRPV1 subpopulation involved in physiological and protective roles, thus increasing their potential therapeutic use.http://www.mdpi.com/1424-8247/5/1/16/TRP channelsnociceptorpainanalgesiaallosteric modulatorsreceptor exocytosisprotein-protein interactionsnovel targets |
| spellingShingle | Antonio Ferrer-Montiel José Manuel González-Ros Isabel Devesa Asia Fernández-Carvajal Gregorio Fernández-Ballester New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View Pharmaceuticals TRP channels nociceptor pain analgesia allosteric modulators receptor exocytosis protein-protein interactions novel targets |
| title | New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View |
| title_full | New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View |
| title_fullStr | New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View |
| title_full_unstemmed | New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View |
| title_short | New Strategies to Develop Novel Pain Therapies: Addressing Thermoreceptors from Different Points of View |
| title_sort | new strategies to develop novel pain therapies addressing thermoreceptors from different points of view |
| topic | TRP channels nociceptor pain analgesia allosteric modulators receptor exocytosis protein-protein interactions novel targets |
| url | http://www.mdpi.com/1424-8247/5/1/16/ |
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