Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy
<p dir="ltr">Diabetic peripheral neuropathic pain (DPNP) is a debilitating complication of longstanding type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. DPNP patients experience mechanical and thermal pain hypersensitivity. Despite its clinical significance and high prevalence, tre...
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2025
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| _version_ | 1864513521699520512 |
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| author | Dina Elsayegh (23739912) |
| author2 | Omar Tluli (23739915) Maram Elzayyat (22928644) Abdelrahman Karen (23739918) Layan Albarghouthi (23739921) Abdulla Al-Emadi (23739924) Mubarak AlMaadid (23739927) Haya Al-Mohannadi (20362818) Laiche Djouhri (112613) |
| author2_role | author author author author author author author author |
| author_facet | Dina Elsayegh (23739912) Omar Tluli (23739915) Maram Elzayyat (22928644) Abdelrahman Karen (23739918) Layan Albarghouthi (23739921) Abdulla Al-Emadi (23739924) Mubarak AlMaadid (23739927) Haya Al-Mohannadi (20362818) Laiche Djouhri (112613) |
| author_role | author |
| dc.creator.none.fl_str_mv | Dina Elsayegh (23739912) Omar Tluli (23739915) Maram Elzayyat (22928644) Abdelrahman Karen (23739918) Layan Albarghouthi (23739921) Abdulla Al-Emadi (23739924) Mubarak AlMaadid (23739927) Haya Al-Mohannadi (20362818) Laiche Djouhri (112613) |
| dc.date.none.fl_str_mv | 2025-11-19T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1080/1061186x.2025.2587701 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Ivabradine_a_hyperpolarization-activated_channel_blocker_attenuates_mechanical_but_not_heat_hypersensitivity_in_hyperglycaemic_and_normoglycemic_rat_models_of_diabetic_neuropathy/32033943 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Pharmacology and pharmaceutical sciences Diabetic peripheral neuropathy neuropathic pain pain hypersensitivity hyperpolarization-activated cyclic nucleotide-gated (HCN) channels ivabradine mechanical allodynia thermal hyperalgesia streptozotocin (STZ) |
| dc.title.none.fl_str_mv | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Diabetic peripheral neuropathic pain (DPNP) is a debilitating complication of longstanding type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. DPNP patients experience mechanical and thermal pain hypersensitivity. Despite its clinical significance and high prevalence, treatment for DPNP remains challenging due to its unclear pathogenesis. We investigated whether hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, known to be involved in other PNP types, also contribute to DPNP. We used two DPNP rat models: (a) streptozotocin (STZ) model of T1DM induced by a single STZ injection (60 mg/kg, i.p.), and (b) high fat diet-fed STZ model (HFD/STZ) of T2DM induced by feeding the rats with HFD (60% calories as fat) for 2 weeks followed by a low-dose STZ injection (35 mg/kg, i.p.). We found that: (a) diabetic (hyperglycaemic) and non-diabetic (normoglycemic) STZ rats, as well as normoglycemic HFD/ZTZ rats, exhibit mechanical and heat hypersensitivity, evidenced by reduced paw withdrawal thresholds and latencies, respectively, and (b) ivabradine (10 mg/kg, i.p.), the clinically approved HCN blocker, was as effective as the positive control gabapentin in attenuating mechanical, but not heat, hypersensitivity, in both models. These findings reinforce that factors beyond hyperglycaemia contribute to DPNP and highlight HCN channels as potential therapeutic targets for treating DPNP.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Journal of Drug Targeting<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1080/1061186x.2025.2587701" target="_blank">https://dx.doi.org/10.1080/1061186x.2025.2587701</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_3fe9efa1780923229fcce1956fc26471 |
| identifier_str_mv | 10.1080/1061186x.2025.2587701 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/32033943 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathyDina Elsayegh (23739912)Omar Tluli (23739915)Maram Elzayyat (22928644)Abdelrahman Karen (23739918)Layan Albarghouthi (23739921)Abdulla Al-Emadi (23739924)Mubarak AlMaadid (23739927)Haya Al-Mohannadi (20362818)Laiche Djouhri (112613)Biomedical and clinical sciencesMedical biochemistry and metabolomicsNeurosciencesPharmacology and pharmaceutical sciencesDiabetic peripheral neuropathyneuropathic painpain hypersensitivityhyperpolarization-activated cyclic nucleotide-gated (HCN) channelsivabradinemechanical allodyniathermal hyperalgesiastreptozotocin (STZ)<p dir="ltr">Diabetic peripheral neuropathic pain (DPNP) is a debilitating complication of longstanding type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. DPNP patients experience mechanical and thermal pain hypersensitivity. Despite its clinical significance and high prevalence, treatment for DPNP remains challenging due to its unclear pathogenesis. We investigated whether hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, known to be involved in other PNP types, also contribute to DPNP. We used two DPNP rat models: (a) streptozotocin (STZ) model of T1DM induced by a single STZ injection (60 mg/kg, i.p.), and (b) high fat diet-fed STZ model (HFD/STZ) of T2DM induced by feeding the rats with HFD (60% calories as fat) for 2 weeks followed by a low-dose STZ injection (35 mg/kg, i.p.). We found that: (a) diabetic (hyperglycaemic) and non-diabetic (normoglycemic) STZ rats, as well as normoglycemic HFD/ZTZ rats, exhibit mechanical and heat hypersensitivity, evidenced by reduced paw withdrawal thresholds and latencies, respectively, and (b) ivabradine (10 mg/kg, i.p.), the clinically approved HCN blocker, was as effective as the positive control gabapentin in attenuating mechanical, but not heat, hypersensitivity, in both models. These findings reinforce that factors beyond hyperglycaemia contribute to DPNP and highlight HCN channels as potential therapeutic targets for treating DPNP.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Journal of Drug Targeting<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1080/1061186x.2025.2587701" target="_blank">https://dx.doi.org/10.1080/1061186x.2025.2587701</a></p>2025-11-19T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1080/1061186x.2025.2587701https://figshare.com/articles/journal_contribution/Ivabradine_a_hyperpolarization-activated_channel_blocker_attenuates_mechanical_but_not_heat_hypersensitivity_in_hyperglycaemic_and_normoglycemic_rat_models_of_diabetic_neuropathy/32033943CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/320339432025-11-19T09:00:00Z |
| spellingShingle | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy Dina Elsayegh (23739912) Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Pharmacology and pharmaceutical sciences Diabetic peripheral neuropathy neuropathic pain pain hypersensitivity hyperpolarization-activated cyclic nucleotide-gated (HCN) channels ivabradine mechanical allodynia thermal hyperalgesia streptozotocin (STZ) |
| status_str | publishedVersion |
| title | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| title_full | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| title_fullStr | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| title_full_unstemmed | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| title_short | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| title_sort | Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycaemic and normoglycemic rat models of diabetic neuropathy |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Pharmacology and pharmaceutical sciences Diabetic peripheral neuropathy neuropathic pain pain hypersensitivity hyperpolarization-activated cyclic nucleotide-gated (HCN) channels ivabradine mechanical allodynia thermal hyperalgesia streptozotocin (STZ) |