{"doi":"10.1016/j.bja.2021.02.035","title":"Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice","abstract":"Background Little is known about the targets in the CNS that mediate ethanol analgesia. This study explores the role of spinal astrocyte aldehyde dehydrogenase-2 (ALDH2), a key ethanol-metabolising enzyme, in the analgesic effects of ethanol in mice. Methods Astrocyte and hepatocyte ALHD2-deficient mice were generated and tested in acute and chronic pain models. Cell-type-specific distribution of ALDH2 was analysed by RNA in situ hybridisation in spinal slices from astrocytic ALDH2-deficient mice and their wild-type littermates. Spinal ethanol metabolites and γ-aminobutyric acid (GABA) content were measured using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Results ALDH2 mRNA was expressed in both astrocytes and neurones in spinal cord slices. Astrocyte ALDH2-deficient mice had decreased expression of ALDH2 mRNA in astrocytes, but not in neurones. Astrocyte ALDH2 deficiency inhibited ethanol-derived acetate, but not acetaldehyde content in spinal cord tissues. Depletion of spinal astrocyte ALDH2 selectively inhibited ethanol-induced anti-nociceptive effect, but not the effect of ethanol, on motor function. Astrocyte ALDH2 deficiency abolished ethanol-induced GABA elevation. The ethanol metabolite acetate produced anti-nociception and increased GABA synthesis in a manner similar to ethanol. I.T. delivery of either GABA A or GABA B receptor antagonists prevented ethanol and acetate-induced analgesia. Conclusions These findings provide evidence that ALDH2 in spinal astrocytes mediates spinal ethanol metabolism and ethanol-induced analgesic effects by promoting GABA synthesis and GABAergic transmission in spinal cord.","journal":"British Journal of Anaesthesia","year":2021,"id":177301,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9642,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260243,"name":"Reşat Çınar","orcid":"0000-0002-8597-7253","position":1,"is_corresponding":false},{"id":720989,"name":"Xudong Hu","orcid":"0000-0002-4297-8360","position":2,"is_corresponding":false},{"id":632920,"name":"Yuhong Lin","orcid":"0009-0000-5267-665X","position":3,"is_corresponding":false},{"id":662830,"name":"Guoxiang Luo","orcid":null,"position":4,"is_corresponding":false},{"id":263789,"name":"David M. Lovinger","orcid":"0000-0002-5454-6725","position":5,"is_corresponding":false},{"id":528251,"name":"Ye Zhang","orcid":"0000-0002-0627-7057","position":6,"is_corresponding":false},{"id":355262,"name":"Li Zhang","orcid":"0000-0002-7700-7345","position":7,"is_corresponding":false},{"id":632916,"name":"Shiyun Jin","orcid":"0000-0003-2610-3318","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:28.018172Z","pmid":"33934892","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":[]}