Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist
Transient receptor potential vanilloid 1 (TRPV1) channels contribute to the development of several chronic pain states and represent a possible therapeutic target in many painful disease treatment. Proinflammatory mediator bradykinin (BK) sensitizes TRPV1, whereas noxious peripheral stimulation incr...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3712 |
| _version_ | 1797539064359944192 |
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| author | Eva Uchytilova Diana Spicarova Jiri Palecek |
| author_facet | Eva Uchytilova Diana Spicarova Jiri Palecek |
| author_sort | Eva Uchytilova |
| collection | DOAJ |
| description | Transient receptor potential vanilloid 1 (TRPV1) channels contribute to the development of several chronic pain states and represent a possible therapeutic target in many painful disease treatment. Proinflammatory mediator bradykinin (BK) sensitizes TRPV1, whereas noxious peripheral stimulation increases BK level in the spinal cord. Here, we investigated the involvement of spinal TRPV1 in thermal and mechanical hypersensitivity, evoked by intrathecal (i.t.) administration of BK and an endogenous agonist of TRPV1, N-oleoyldopamine (OLDA), using behavioral tests and i.t. catheter implantation, and administration of BK-induced transient thermal and mechanical hyperalgesia and mechanical allodynia. All these hypersensitive states were enhanced by co-administration of a low dose of OLDA (0.42 µg i.t.), which was ineffective only under the control conditions. Intrathecal pretreatment with TRPV1 selective antagonist SB366791 prevented hypersensitivity induced by i.t. co-administration of BK and OLDA. Our results demonstrate that both thermal and mechanical hypersensitivity evoked by co-administration of BK and OLDA is mediated by the activation of spinal TRPV1 channels. |
| first_indexed | 2024-03-10T12:40:04Z |
| format | Article |
| id | doaj.art-df9139c637d24bcf92a354126186f5ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:40:04Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-df9139c637d24bcf92a354126186f5ba2023-11-21T13:59:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01227371210.3390/ijms22073712Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 AntagonistEva Uchytilova0Diana Spicarova1Jiri Palecek2Laboratory of Pain Research, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech RepublicLaboratory of Pain Research, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech RepublicLaboratory of Pain Research, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech RepublicTransient receptor potential vanilloid 1 (TRPV1) channels contribute to the development of several chronic pain states and represent a possible therapeutic target in many painful disease treatment. Proinflammatory mediator bradykinin (BK) sensitizes TRPV1, whereas noxious peripheral stimulation increases BK level in the spinal cord. Here, we investigated the involvement of spinal TRPV1 in thermal and mechanical hypersensitivity, evoked by intrathecal (i.t.) administration of BK and an endogenous agonist of TRPV1, N-oleoyldopamine (OLDA), using behavioral tests and i.t. catheter implantation, and administration of BK-induced transient thermal and mechanical hyperalgesia and mechanical allodynia. All these hypersensitive states were enhanced by co-administration of a low dose of OLDA (0.42 µg i.t.), which was ineffective only under the control conditions. Intrathecal pretreatment with TRPV1 selective antagonist SB366791 prevented hypersensitivity induced by i.t. co-administration of BK and OLDA. Our results demonstrate that both thermal and mechanical hypersensitivity evoked by co-administration of BK and OLDA is mediated by the activation of spinal TRPV1 channels.https://www.mdpi.com/1422-0067/22/7/3712TRPV1bradykininOLDAspinal cordhyperalgesiaallodynia |
| spellingShingle | Eva Uchytilova Diana Spicarova Jiri Palecek Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist International Journal of Molecular Sciences TRPV1 bradykinin OLDA spinal cord hyperalgesia allodynia |
| title | Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist |
| title_full | Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist |
| title_fullStr | Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist |
| title_full_unstemmed | Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist |
| title_short | Hypersensitivity Induced by Intrathecal Bradykinin Administration Is Enhanced by N-oleoyldopamine (OLDA) and Prevented by TRPV1 Antagonist |
| title_sort | hypersensitivity induced by intrathecal bradykinin administration is enhanced by n oleoyldopamine olda and prevented by trpv1 antagonist |
| topic | TRPV1 bradykinin OLDA spinal cord hyperalgesia allodynia |
| url | https://www.mdpi.com/1422-0067/22/7/3712 |
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