Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy
The peripheral effects of ω-conotoxins, selective blockers of N-type voltage-gated calcium channels (Ca<sub>V</sub>2.2), have not been characterised across different clinically relevant pain models. This study examines the effects of locally administered ω-conotoxin MVIIA, GVIA, and CVIF...
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MDPI AG
2021-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/2/106 |
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| author | Md. Mahadhi Hasan Hana Starobova Alexander Mueller Irina Vetter Richard J. Lewis |
| author_facet | Md. Mahadhi Hasan Hana Starobova Alexander Mueller Irina Vetter Richard J. Lewis |
| author_sort | Md. Mahadhi Hasan |
| collection | DOAJ |
| description | The peripheral effects of ω-conotoxins, selective blockers of N-type voltage-gated calcium channels (Ca<sub>V</sub>2.2), have not been characterised across different clinically relevant pain models. This study examines the effects of locally administered ω-conotoxin MVIIA, GVIA, and CVIF on mechanical and thermal paw withdrawal threshold (PWT) in postsurgical pain (PSP), cisplatin-induced neuropathy (CisIPN), and oxaliplatin-induced neuropathy (OIPN) rodent models. Intraplantar injection of 300, 100 and 30 nM MVIIA significantly (<i>p</i> < 0.0001, <i>p</i> < 0.0001, and <i>p</i> < 0.05, respectively) alleviated mechanical allodynia of mice in PSP model compared to vehicle control group. Similarly, intraplantar injection of 300, 100, and 30 nM MVIIA (<i>p</i> < 0.0001, <i>p</i> < 0.01, and <i>p</i> < 0.05, respectively), and 300 nM and 100 nM GVIA (<i>p</i> < 0.0001 and <i>p</i> < 0.05, respectively) significantly increased mechanical thresholds of mice in OIPN model. The ED<sub>50</sub> of GVIA and MVIIA in OIPN was found to be 1.8 pmol/paw and 0.8 pmol/paw, respectively. However, none of the ω-conotoxins were effective in a mouse model of CisIPN. The intraplantar administration of 300 nM GVIA, MVIIA, and CVIF did not cause any locomotor side effects. The intraplantar administration of MVIIA can alleviate incision-induced mechanical allodynia, and GVIA and MVIIA effectively reduce OIPN associated mechanical pain, without locomotor side effects, in rodent models. In contrast, CVIF was inactive in these pain models, suggesting it is unable to block a subset of N-type voltage-gated calcium channels associated with nociceptors in the skin. |
| first_indexed | 2024-03-09T00:57:47Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T00:57:47Z |
| publishDate | 2021-02-01 |
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| series | Marine Drugs |
| spelling | doaj.art-896645174b7340bca1d4df5a890ce33f2023-12-11T16:46:25ZengMDPI AGMarine Drugs1660-33972021-02-0119210610.3390/md19020106Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral NeuropathyMd. Mahadhi Hasan0Hana Starobova1Alexander Mueller2Irina Vetter3Richard J. Lewis4Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaThe peripheral effects of ω-conotoxins, selective blockers of N-type voltage-gated calcium channels (Ca<sub>V</sub>2.2), have not been characterised across different clinically relevant pain models. This study examines the effects of locally administered ω-conotoxin MVIIA, GVIA, and CVIF on mechanical and thermal paw withdrawal threshold (PWT) in postsurgical pain (PSP), cisplatin-induced neuropathy (CisIPN), and oxaliplatin-induced neuropathy (OIPN) rodent models. Intraplantar injection of 300, 100 and 30 nM MVIIA significantly (<i>p</i> < 0.0001, <i>p</i> < 0.0001, and <i>p</i> < 0.05, respectively) alleviated mechanical allodynia of mice in PSP model compared to vehicle control group. Similarly, intraplantar injection of 300, 100, and 30 nM MVIIA (<i>p</i> < 0.0001, <i>p</i> < 0.01, and <i>p</i> < 0.05, respectively), and 300 nM and 100 nM GVIA (<i>p</i> < 0.0001 and <i>p</i> < 0.05, respectively) significantly increased mechanical thresholds of mice in OIPN model. The ED<sub>50</sub> of GVIA and MVIIA in OIPN was found to be 1.8 pmol/paw and 0.8 pmol/paw, respectively. However, none of the ω-conotoxins were effective in a mouse model of CisIPN. The intraplantar administration of 300 nM GVIA, MVIIA, and CVIF did not cause any locomotor side effects. The intraplantar administration of MVIIA can alleviate incision-induced mechanical allodynia, and GVIA and MVIIA effectively reduce OIPN associated mechanical pain, without locomotor side effects, in rodent models. In contrast, CVIF was inactive in these pain models, suggesting it is unable to block a subset of N-type voltage-gated calcium channels associated with nociceptors in the skin.https://www.mdpi.com/1660-3397/19/2/106ω-conotoxinschemotherapy-induced peripheral neuropathypostsurgical painintraplantar administration |
| spellingShingle | Md. Mahadhi Hasan Hana Starobova Alexander Mueller Irina Vetter Richard J. Lewis Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy Marine Drugs ω-conotoxins chemotherapy-induced peripheral neuropathy postsurgical pain intraplantar administration |
| title | Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy |
| title_full | Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy |
| title_fullStr | Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy |
| title_full_unstemmed | Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy |
| title_short | Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy |
| title_sort | subcutaneous ω conotoxins alleviate mechanical pain in rodent models of acute peripheral neuropathy |
| topic | ω-conotoxins chemotherapy-induced peripheral neuropathy postsurgical pain intraplantar administration |
| url | https://www.mdpi.com/1660-3397/19/2/106 |
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