Alleviating morphine-induced itching while sustaining its analgesic efficacy: Esketamine as a potential co-administrating choice

Morphine is one of the most commonly used and effective analgesic drugs in clinical practice. Morphine injected directly into the epidural and subarachnoid space acts directly on the central nervous system compared to oral or intravenous administration. This route of morphine delivery requires only a small dose to achieve satisfactory analgesia and greatly reduces the risk of adverse effects. However, morphine-induced itching significantly limits the clinical use of morphine and the maximization of its analgesic effects. Drugs commonly used worldwide to treat morphine-induced pruritus have different degrees of limitations. N-Methyl-D-aspartate (NMDA) receptors are involved in the mechanisms associated with morphine-induced itching. Theoretically, esketamine, an NMDA antagonist, which is commonly used in clinical practice to exert analgesic and sedative effects and contributes to circulatory stability, has the potential to effectively relieve morphine-induced itching without compromising its analgesic effects. In this paper, we discuss the possibility of co-administration of esketamine in cases of morphine-induced pruritus based on the current clinical situation and relevant mechanisms, with the intention of developing novel therapeutic options for morphine-induced pruritus.