Mechanism, Dose, and Administration of Dexmedetomidine in Managing Visceral Pain Associated With Surgery: A Narrative Review.

Many individuals remain unaware of the intricate functions performed by their internal organs. Each organ has distinct physiological functions, and as long as life persists, these complex regulatory processes operate continuously [ 1 ]. Most internal organs in the human body are richly innervated, comprising both afferent and efferent nerve fibers [ 2 , 3 ]. In the event of an anomaly or perceived adverse condition, these organs can sense and recognize the disturbance, promptly making adaptive changes or issuing a series of early warning signals to alert the body, thereby triggering appropriate responses [ 4 , 5 ]. Visceral pain refers to discomfort originating from the internal organs, particularly those within the thoracic and abdominal cavities [ 6 ]. This type of pain can manifest as either acute or chronic and is characterized by its poorly localized nature [ 6 ]. It typically develops gradually and persists for extended periods. Unlike somatic/cutaneous pain, visceral pain lacks sharp sensations; it is insensate to cuts and burns but sensitive to traction, distension, and ischemic injuries [ 4 , 7 ]. Furthermore, it frequently presents with referred pain and pronounced autonomic reflexes [ 3 ]. Consequently, visceral pain is debilitating and often difficult to treat. Patients experiencing this type of pain endure varying degrees of discomfort, which can lead to psychological issues, escalate healthcare costs, and diminish overall quality of life [ 8 ]. In clinical practice, managing refractory visceral pain often necessitates a combination of pharmacological agents and therapeutic techniques [ 9 – 11 ]. The clinical challenge lies in the complex pathophysiology of visceral pain [ 6 ], which involves hypersensitivity to stimuli like distension and is often complicated by significant autonomic reflexes. Dexmedetomidine (DEX) is uniquely suited to this complexity, as its multifaceted pharmacological profile directly targets these underlying mechanisms. Recent studies have highlighted the potential of DEX, a highly selective alpha-2 adrenergic receptor (α 2 -ARs) agonist known for its sedative [ 12 ], analgesic, anxiolytic, anti-inflammatory [ 13 ], and intestinal barrier-protective properties [ 14 , 15 ], to alleviate visceral pain. Despite its growing recognition, a comprehensive synthesis of findings regarding the use of DEX in treating visceral pain remains lacking. This article reviews the mechanisms, dose, and modes of administration of DEX in managing visceral pain associated with surgery, and highlights the potential of DEX for clinical application and future research.

Although multiple modes of administration have been investigated for DEX, obtaining seemingly promising results, several aspects should be further delineated for translation into clinical applications: (1) whether there are appropriate modes and doses for the administration of DEX under different routes; (2) additive effects and the safety margin of DEX for visceral pain; (3) consideration of the proportion of first-pass elimination when administering DEX intraperitoneally; (4) whether DEX affects the overall prognosis or even promotes metastasis when used as an adjuvant for long-time intravenous analgesia in patients with cancer after surgery [ 126 , 127 ]; and (5) DEX-mediated immunomodulation offers an interesting perioperative therapeutic option for patients with cancer [ 66 ]. These limited data underscore the need for large-scale, high-quality clinical studies to elucidate the impact of DEX on visceral pain in various types of surgery.

In summary, DEX, a highly selective alpha-2 adrenergic receptor (α 2 -ARs) agonist (α 2 : α 1 =1600: 1) with sedative, analgesic, anti-inflammation, sympatholytic properties, can be a useful adjuvant for visceral pain associated with surgery. DEX can be used via intravenous injections, intraspinal administration, intraperitoneal spraying, or other routes for alleviating pain. Recent animal studies and clinical research have confirmed that DEX plays a vital role in managing visceral pain through multiple mechanisms. However, it remains undetermined whether there is a single primary mechanism or if it is a combination of several effects. Hence, large-scale, high-quality clinical trials are needed to clarify its effects in combating both chronic and acute visceral pain in clinical practice.