{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:53:06Z","timestamp":1792979586622,"version":"4.5.0"},"reference-count":151,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Opioids are widely used in cancer and non-cancer pain management. However, many transporters at the blood\u2013brain barrier (BBB), such as P-glycoprotein (P-gp, ABCB1\/MDR1), may impair their delivery to the brain, thus leading to opioid tolerance. Nonetheless, opioids may regulate P-gp expression, thus altering the transport of other compounds, namely chemotherapeutic agents, resulting in pharmacoresistance. Other kinds of painkillers (e.g., acetaminophen, dexamethasone) and adjuvant drugs used for neuropathic pain may act as P-gp substrates and modulate its expression, thus making pain management challenging. Inflammatory conditions are also believed to upregulate P-gp. The role of P-gp in drug\u2013drug interactions is currently under investigation, since many P-gp substrates may also act as substrates for the cytochrome P450 enzymes, which metabolize a wide range of xenobiotics and endobiotics. Genetic variability of the ABCB1\/MDR1 gene may be accountable for inter-individual variation in opioid-induced analgesia. P-gp also plays a role in the management of opioid-induced adverse effects, such as constipation. Peripherally acting mu-opioid receptors antagonists (PAMORAs), such as naloxegol and naldemedine, are substrates of P-gp, which prevent their penetration in the central nervous system. In our review, we explore the interactions between P-gp and opioidergic drugs, with their implications in clinical practice.<\/jats:p>","DOI":"10.3390\/ijms232214125","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:24:53Z","timestamp":1668565493000},"page":"14125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Impact of P-Glycoprotein on Opioid Analgesics: What\u2019s the Real Meaning in Pain Management and Palliative Care?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-5519","authenticated-orcid":false,"given":"Flaminia","family":"Coluzzi","sequence":"first","affiliation":[{"name":"Department Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, 04100 Latina, Italy"},{"name":"Unit of Anaesthesia, Intensive Care, and Pain Medicine, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sole","family":"Scerpa","sequence":"additional","affiliation":[{"name":"Unit of Anaesthesia, Intensive Care, and Pain Medicine, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-3607","authenticated-orcid":false,"given":"Monica","family":"Rocco","sequence":"additional","affiliation":[{"name":"Unit of Anaesthesia, Intensive Care, and Pain Medicine, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"},{"name":"Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Fornasari","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s40122-021-00272-x","article-title":"Factors Influencing Pain Expression in Patients with Cancer: An Expert Opinion","volume":"10","author":"Mercadante","year":"2021","journal-title":"Pain Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s40122-021-00248-x","article-title":"Personalizing Cancer Pain Therapy: Insights from the Rational Use of Analgesics (RUA) Group","volume":"10","author":"Varrassi","year":"2021","journal-title":"Pain Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.2174\/1570159X15666170504095823","article-title":"Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain","volume":"15","author":"Chaves","year":"2017","journal-title":"Curr. 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