Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy
<p dir="ltr">Diabetic peripheral neuropathy (DPN) is the most incapacitating complication of diabetes mellitus. Up to 50% of patients with DPN develop peripheral neuropathic pain (PNP). The underlying ionic and molecular mechanisms of diabetic PNP (DPNP) are poorly understood. Howeve...
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2019
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| _version_ | 1864513520312254464 |
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| author | Laiche Djouhri (112613) |
| author2 | Mohammed Imad Malki (9649555) Asad Zeidan (8879705) Karim Nagi (11414276) Trevor Smith (5728859) |
| author2_role | author author author author |
| author_facet | Laiche Djouhri (112613) Mohammed Imad Malki (9649555) Asad Zeidan (8879705) Karim Nagi (11414276) Trevor Smith (5728859) |
| author_role | author |
| dc.creator.none.fl_str_mv | Laiche Djouhri (112613) Mohammed Imad Malki (9649555) Asad Zeidan (8879705) Karim Nagi (11414276) Trevor Smith (5728859) |
| dc.date.none.fl_str_mv | 2019-05-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1080/1061186x.2019.1608552 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Activation_of_K_sub_v_sub_7_channels_with_the_anticonvulsant_retigabine_alleviates_neuropathic_pain_behaviour_in_the_streptozotocin_rat_model_of_diabetic_neuropathy_sub_v_sub_7_channels_with_the_anticonvulsant_retigabine_alleviates_neuropat/25427683 |
| 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 Pharmacology and pharmaceutical sciences Diabetic neuropathy chronic pain pain hypersensitivity behaviour neuropathic pain |
| dc.title.none.fl_str_mv | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model 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 neuropathy (DPN) is the most incapacitating complication of diabetes mellitus. Up to 50% of patients with DPN develop peripheral neuropathic pain (PNP). The underlying ionic and molecular mechanisms of diabetic PNP (DPNP) are poorly understood. However, voltage gated potassium (K<sub>v</sub>7) channels which have been implicated in the pathogenesis of other types of PNP are likely to be involved. Here we examined, in the streptozotocin (STZ) rat model of DPNP, whether activating the Kv7 channels with a potent activator retigabine (ezogabine) would reverse/attenuate behavioural signs of DPNP. STZ rats exhibited behavioural indices of mechanical and heat hypersensitivity, but not cold hypersensitivity or spontaneous pain, 35 days after STZ injection. Retigabine given at a dose of 15 mg/kg (but not at 7.5 mg/kg, i.p.) significantly attenuated mechanical, but not heat hypersensitivity in DPNP rats, and was as effective as the positive control gabapentin. This analgesic effect of retigabine was completely reversed by the K<sub>v</sub>7/M channel blocker XE991 (3 mg/kg, i.p.) indicating that the anti-allodynic effects of retigabine were mediated by K<sub>v</sub>7 channels. In conclusion, the findings suggest that Kv7 channels are involved in DPNP pathogenesis, and that strategies that target their activation may prove to be effective in treating DPNP.</p><h2>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.2019.1608552" target="_blank">https://dx.doi.org/10.1080/1061186x.2019.1608552</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_1e3d97c5427d76cb65a4b8362fc12a17 |
| identifier_str_mv | 10.1080/1061186x.2019.1608552 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25427683 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathyLaiche Djouhri (112613)Mohammed Imad Malki (9649555)Asad Zeidan (8879705)Karim Nagi (11414276)Trevor Smith (5728859)Biomedical and clinical sciencesPharmacology and pharmaceutical sciencesDiabetic neuropathychronic painpain hypersensitivitybehaviourneuropathic pain<p dir="ltr">Diabetic peripheral neuropathy (DPN) is the most incapacitating complication of diabetes mellitus. Up to 50% of patients with DPN develop peripheral neuropathic pain (PNP). The underlying ionic and molecular mechanisms of diabetic PNP (DPNP) are poorly understood. However, voltage gated potassium (K<sub>v</sub>7) channels which have been implicated in the pathogenesis of other types of PNP are likely to be involved. Here we examined, in the streptozotocin (STZ) rat model of DPNP, whether activating the Kv7 channels with a potent activator retigabine (ezogabine) would reverse/attenuate behavioural signs of DPNP. STZ rats exhibited behavioural indices of mechanical and heat hypersensitivity, but not cold hypersensitivity or spontaneous pain, 35 days after STZ injection. Retigabine given at a dose of 15 mg/kg (but not at 7.5 mg/kg, i.p.) significantly attenuated mechanical, but not heat hypersensitivity in DPNP rats, and was as effective as the positive control gabapentin. This analgesic effect of retigabine was completely reversed by the K<sub>v</sub>7/M channel blocker XE991 (3 mg/kg, i.p.) indicating that the anti-allodynic effects of retigabine were mediated by K<sub>v</sub>7 channels. In conclusion, the findings suggest that Kv7 channels are involved in DPNP pathogenesis, and that strategies that target their activation may prove to be effective in treating DPNP.</p><h2>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.2019.1608552" target="_blank">https://dx.doi.org/10.1080/1061186x.2019.1608552</a></p>2019-05-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1080/1061186x.2019.1608552https://figshare.com/articles/journal_contribution/Activation_of_K_sub_v_sub_7_channels_with_the_anticonvulsant_retigabine_alleviates_neuropathic_pain_behaviour_in_the_streptozotocin_rat_model_of_diabetic_neuropathy_sub_v_sub_7_channels_with_the_anticonvulsant_retigabine_alleviates_neuropat/25427683CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/254276832019-05-06T03:00:00Z |
| spellingShingle | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy Laiche Djouhri (112613) Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Diabetic neuropathy chronic pain pain hypersensitivity behaviour neuropathic pain |
| status_str | publishedVersion |
| title | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| title_full | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| title_fullStr | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| title_full_unstemmed | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| title_short | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| title_sort | Activation of K<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy<sub>v</sub>7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy |
| topic | Biomedical and clinical sciences Pharmacology and pharmaceutical sciences Diabetic neuropathy chronic pain pain hypersensitivity behaviour neuropathic pain |