{"doi":"10.1093/jscdis/yoaf033","title":"Behavioral and transcriptional effects of age in HbSS-BERK humanized SCD mice","abstract":"Objectives: SCD is associated with morbidity, mortality, and severe pain that is well modeled in humanized Berkeley SCD (HbSS) mice. Here, we conducted a comprehensive study to evaluate the effects of age on the development of the HbSS hyper-nociceptive phenotype. We also examined the antinociceptive effects of oxycodone, a commonly used analgesics to manage SCD-related pain, in both genotypes. Methods: Mixed sex, 2-, 5-, and 10-month HbSS and HbAA control mice were assessed in cadre of stimulus-evoked and non-evoked functional assays. The dose-response relationship of oxycodone was evaluated in 10-month mice from both genotypes in a subset of in vivo assays. Finally, qRT-PCR was used to quantify the relative mRNA levels of opioid receptors and ligand precursors, and pro-inflammatory cytokines, from spinal cord and dorsal root ganglia. Results: HbSS mice displayed augmented responses in stimulus-evoked assays and deficits in non-evoked functional behaviors that overall worsened in severity over age, compared with controls. Oxycodone dose-dependently attenuated mechanical hypersensitivity and produced thermal antinociception but failed to normalize (or worsened) functional behavior. Finally, HbSS mice exhibited overall or age-dependent differences in mRNA amounts of mu and kappa opioid receptors, POMC, IL-1β, and IL-6. Conclusions: This study offers a comprehensive approach to investigate candidate drugs to treat SCD pain and explores biomarkers associated with the HbSS SCD mouse model. Although oxycodone ameliorated the hyper-nociceptive phenotype of HbSS mice, it failed to restore functional behavior, underscoring the need to identify novel therapeutic strategies that effectively reduce pain and restore functional behavior.","journal":"Journal of sickle cell disease.","year":2025,"id":577214,"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":0.8391,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1369651,"name":"M. Taylor","orcid":"0000-0002-2739-4463","position":1,"is_corresponding":false},{"id":913318,"name":"Bryan McKiver","orcid":"0000-0002-1447-5803","position":2,"is_corresponding":false},{"id":726060,"name":"Karan H. Muchhala","orcid":"0000-0002-2594-1347","position":3,"is_corresponding":false},{"id":1486751,"name":"Molly Sonenklar","orcid":null,"position":4,"is_corresponding":false},{"id":1486391,"name":"Adwoa Agyemang Adu-Gyamfi","orcid":"0000-0001-7921-8800","position":5,"is_corresponding":false},{"id":1109101,"name":"Sara M Herz","orcid":"0009-0004-8763-5670","position":6,"is_corresponding":false},{"id":1486392,"name":"Dawn K Jessup","orcid":"0000-0001-9104-7151","position":7,"is_corresponding":false},{"id":607928,"name":"Joyce A. Lloyd","orcid":"0000-0003-0952-9923","position":8,"is_corresponding":false},{"id":726061,"name":"Hamid I. Akbarali","orcid":"0000-0003-1423-0774","position":9,"is_corresponding":false},{"id":755671,"name":"M. Imad Damaj","orcid":"0000-0002-8859-029X","position":10,"is_corresponding":false},{"id":304394,"name":"Kalpna Gupta","orcid":"0000-0001-9381-9979","position":11,"is_corresponding":false},{"id":593432,"name":"Wally R. Smith","orcid":"0000-0002-4122-5367","position":12,"is_corresponding":false},{"id":284798,"name":"Aron H. Lichtman","orcid":"0000-0001-5601-985X","position":13,"is_corresponding":false},{"id":1341630,"name":"Kennedy Goldsborough","orcid":"0000-0001-9403-2721","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:58:04.622308Z","pmid":"41244884","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":[]}