The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy
Treating pain in patients suffering from small fiber neuropathies still represents a therapeutic challenge for health care providers and drug developers worldwide. Unfortunately, none of the currently available treatments can completely reverse symptoms of either gain or loss of peripheral nerve sen...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-03-01
|
| Series: | Frontiers in Pain Research |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpain.2022.869735/full |
| _version_ | 1819205376705298432 |
|---|---|
| author | Sonja L. Joksimovic Vesna Jevtovic-Todorovic Slobodan M. Todorovic Slobodan M. Todorovic |
| author_facet | Sonja L. Joksimovic Vesna Jevtovic-Todorovic Slobodan M. Todorovic Slobodan M. Todorovic |
| author_sort | Sonja L. Joksimovic |
| collection | DOAJ |
| description | Treating pain in patients suffering from small fiber neuropathies still represents a therapeutic challenge for health care providers and drug developers worldwide. Unfortunately, none of the currently available treatments can completely reverse symptoms of either gain or loss of peripheral nerve sensation. Therefore, there is a clear need for novel mechanism-based therapies for peripheral diabetic neuropathy (PDN) that would improve treatment of this serious condition. In this review, we summarize the current knowledge on the mechanisms and causes of peripheral sensory neurons damage in diabetes. In particular, we focused on the subsets of voltage-gated sodium channels, TRP family of ion channels and a CaV3.2 isoform of T-type voltage-gated calcium channels. However, even though their potential is well-validated in multiple rodent models of painful PDN, clinical trials with specific pharmacological blockers of these channels have failed to exhibit therapeutic efficacy. We argue that understanding the development of diabetes and causal relationship between hyperglycemia, glycosylation, and other post-translational modifications may lead to the development of novel therapeutics that would efficiently alleviate painful PDN by targeting disease-specific mechanisms rather than individual nociceptive ion channels. |
| first_indexed | 2024-12-23T04:50:44Z |
| format | Article |
| id | doaj.art-45116cfad83948b78fe8091c2f438936 |
| institution | Directory Open Access Journal |
| issn | 2673-561X |
| language | English |
| last_indexed | 2024-12-23T04:50:44Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pain Research |
| spelling | doaj.art-45116cfad83948b78fe8091c2f4389362022-12-21T17:59:28ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2022-03-01310.3389/fpain.2022.869735869735The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic NeuropathySonja L. Joksimovic0Vesna Jevtovic-Todorovic1Slobodan M. Todorovic2Slobodan M. Todorovic3Department of Anesthesiology, University of Colorado Denver, Aurora, CO, United StatesDepartment of Anesthesiology, University of Colorado Denver, Aurora, CO, United StatesDepartment of Anesthesiology, University of Colorado Denver, Aurora, CO, United StatesNeuroscience Graduate Program, University of Colorado Denver, Aurora, CO, United StatesTreating pain in patients suffering from small fiber neuropathies still represents a therapeutic challenge for health care providers and drug developers worldwide. Unfortunately, none of the currently available treatments can completely reverse symptoms of either gain or loss of peripheral nerve sensation. Therefore, there is a clear need for novel mechanism-based therapies for peripheral diabetic neuropathy (PDN) that would improve treatment of this serious condition. In this review, we summarize the current knowledge on the mechanisms and causes of peripheral sensory neurons damage in diabetes. In particular, we focused on the subsets of voltage-gated sodium channels, TRP family of ion channels and a CaV3.2 isoform of T-type voltage-gated calcium channels. However, even though their potential is well-validated in multiple rodent models of painful PDN, clinical trials with specific pharmacological blockers of these channels have failed to exhibit therapeutic efficacy. We argue that understanding the development of diabetes and causal relationship between hyperglycemia, glycosylation, and other post-translational modifications may lead to the development of novel therapeutics that would efficiently alleviate painful PDN by targeting disease-specific mechanisms rather than individual nociceptive ion channels.https://www.frontiersin.org/articles/10.3389/fpain.2022.869735/fullT-type calcium channel 3.2diabetic neuropathymechanisms of painion channelsplasticity |
| spellingShingle | Sonja L. Joksimovic Vesna Jevtovic-Todorovic Slobodan M. Todorovic Slobodan M. Todorovic The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy Frontiers in Pain Research T-type calcium channel 3.2 diabetic neuropathy mechanisms of pain ion channels plasticity |
| title | The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy |
| title_full | The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy |
| title_fullStr | The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy |
| title_full_unstemmed | The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy |
| title_short | The Mechanisms of Plasticity of Nociceptive Ion Channels in Painful Diabetic Neuropathy |
| title_sort | mechanisms of plasticity of nociceptive ion channels in painful diabetic neuropathy |
| topic | T-type calcium channel 3.2 diabetic neuropathy mechanisms of pain ion channels plasticity |
| url | https://www.frontiersin.org/articles/10.3389/fpain.2022.869735/full |
| work_keys_str_mv | AT sonjaljoksimovic themechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT vesnajevtovictodorovic themechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT slobodanmtodorovic themechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT slobodanmtodorovic themechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT sonjaljoksimovic mechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT vesnajevtovictodorovic mechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT slobodanmtodorovic mechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy AT slobodanmtodorovic mechanismsofplasticityofnociceptiveionchannelsinpainfuldiabeticneuropathy |