{"doi":"10.1101/2024.06.05.596514","title":"Uncoupling the CRMP2-Ca <sub>V</sub> 2.2 interaction reduces pain-like behavior in a preclinical osteoarthritis model","abstract":"Abstract 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":498308,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1040609,"name":"Sara Hestehave","orcid":"0000-0002-1837-521X","position":1,"is_corresponding":false},{"id":880662,"name":"Paz Duran","orcid":"0000-0001-8729-8636","position":2,"is_corresponding":false},{"id":325506,"name":"Tyler S. Nelson","orcid":"0000-0002-6675-4820","position":3,"is_corresponding":false},{"id":254857,"name":"Rajesh Khanna","orcid":"0000-0002-9066-2969","position":4,"is_corresponding":false},{"id":863583,"name":"Heather N. Allen","orcid":"0000-0003-0771-1959","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:09:38.543544Z","pmid":"38895294","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}