Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain

Ferron, Laurent; Harding, Erika K.; Gandini, Maria A.; Brideau, Craig; Stys, Peter K.; Zamponi, Gerald W.

doi:10.1016/j.isci.2024.109973

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2024

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Cited by 2 publications

References 76 publications

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Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Allen,

Hestehave,

Duran

et al. 2024

The Journal of Pain

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Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Allen,

Hestehave,

Duran

et al. 2024

The Journal of Pain

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Uncoupling the CRMP2-Ca_V2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model

Allen,

Hestehave,

Duran

et al. 2024

Preprint

View full text Add to dashboard Cite

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple FDA-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics-invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. We have identified a key regulator of CaV2.2 channels, collapsing response mediator protein 2 (CRMP2), that allows us to indirectly regulate CaV2.2 expression and function. We developed a peptidomimetic modulator of CRMP2, CBD3063, that effectively reverses neuropathic and inflammatory pain without negative side effects by reducing membrane expression of CaV2.2. Using a rodent model of OA, we demonstrate the intraperitoneal administration of CBD3063 alleviates both evoked and non-evoked behavioral hallmarks of OA pain. Further, we reveal that CBD3063 reduces OA-induced increased neural activity in the parabrachial nucleus, a key supraspinal site modulating the pain experience. Together, these studies suggest CBD3063 is an effective analgesic for OA pain.

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Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain

Cited by 2 publications

References 76 publications

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Uncoupling the CRMP2-Ca_V2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model

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Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain

Cited by 2 publications

References 76 publications

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Uncoupling the CRMP2-CaV2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model

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Uncoupling the CRMP2-Ca_V2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model