Postoperative pain (POP) caused by surgical injury to the skin, fascia, mucosa, and small nerves innervating these tissues is a common form of acute clinical pain [1] that has been reported following many different types of surgery. Moreover, 10–50% of patients develop chronic and persistent POP [2]. Of patients who underwent surgery within the past 5 years, 86% experienced POP and 75% experienced moderate or severe pain shortly after surgery [3]. Despite ongoing pain research and the development of different analgesic medications and medical care in the clinic, many surgery patients still experience POP [3,4]. Poor POP management leads to delayed wound healing, insomnia, and anxiety and can significantly affect postoperative recovery, resulting in a huge burden on patients’ personal and financial lives [5].

Local anesthetics (LAs) have a longstanding record of safety and effectiveness in surgical anesthesia and analgesia. By modulating voltage- and ligand-gated channels, receptors, and cellular pathways, LAs block pain transmission to the central nervous system (CNS), producing a somatosensory blockade that forms the basis of neuraxial and peripheral nerve blocks [6]. The main modalities that use LAs to manage pain are peripheral nerve block [7,8], epidural analgesia [9,10], local infiltration [11], and topical anesthesia [12,13]. Owing to local application, the conduction of pain from the wound is reduced, and the local inflammatory response to injury is suppressed [14], thus producing satisfactory analgesic effects and effective opioid savings. Moreover, the local application of LAs as part of a multimodal analgesic regimen is increasingly recommended [15,16].

Although the use of LAs in perioperative management is becoming increasingly popular because of their effective analgesic performance and minimal side effects, their small molecular weight and rapid metabolism result in a short duration of analgesia after a single administration [17]. However, prolonging LAs effects by increasing their dosage or concentration may increase the risk of motor block or local anesthetic systemic toxicity [18,19]. Moreover, in many clinical practices, POP management using LAs has technical limitations. For instance, during the intrathecal infusion of LAs, catheter placement requires professional operation and is prone to catheter displacement, dislodgement, infection, and nerve damage [20]. With the development of materials science and nanotechnology, various LAs delivery platforms have been developed to compensate for these disadvantages. Numerous delivery platforms have been designed to continuously release a safe dose in a single administration to ensure minimal systemic toxicity and prolong pain relief. LAs delivery platforms can also be designed to control the duration and intensity of analgesia according to changes in the external trigger conditions, achieve on-demand analgesia, and significantly improve pain relief and patient satisfaction. Here, we review LAs delivery systems for the management of POP (Figure 1).