Mechanisms of Dexmedetomidine in Neuropathic Pain

Abstract

Dexmedetomidin is a new-generation, highly selective α2 adrenergic receptor agonist with a large number of advantages, including its sedative and analgesic properties, its ability to inhibit sympathetic nerves, its reduced anesthetic dosage, its hemodynamic stability, its mild respiratory depression abilities, and its ability to improve postoperative recognition. Its safety and effectiveness, as well as its ability to provide a certain degree of comfort to patients, make it a useful anesthetic adjuvant for a wide range of clinical applications. For example, dexmedetomidine is commonly used in patients undergoing general anesthesia, and it also exerts sedative effects during tracheal intubation or mechanical ventilation in intensive care unit patients. In recent years, with the deepening of clinical research on dexmedetomidine, the drug is still applied in the treatment of spastic pain, myofascial pain, neuropathic pain, complex pain syndrome, and chronic headache, as well as for multimodal analgesia. However, we must note that the appropriateness of patient and dose selection should be given attention when using this drug; furthermore, patients should be observed for adverse reactions such as hypotension and bradycardia. Therefore, the safety and effectiveness of this drug for long-term use remain to be studied. In addition, basic experimental studies have also found that dexmedetomidine can protect important organs, such as the brain, heart, kidney, liver, and lung, through various mechanisms, such as antisympathetic effects, the inhibition of apoptosis and oxidative stress, and a reduction in the inflammatory response. Moreover, the neuroprotective properties of dexmedetomidine have received the most attention from scholars. Hence, in this review, we mainly focus on the characteristics and clinical applications of dexmedetomidine, especially the role of dexmedetomidine in the nervous system and the use of dexmedetomidine in the relief of neuropathic pain.

Successful peripheral nerve block under dexmedetomidine sedation for femoral neck fracture fixation in a 97-year-old patient

“…We selected DEX as a supplement of the PNB and surgery because DEX is a selective α2 adrenergic receptor agonist with a large number of advantages, including fast-onset sedation with minimal respiratory depression, mild analgesic properties and the ability to improve postoperative recognition. 14 In our patient, we assessed the level of sedation using the OAA/S score, a subjective assessment carried out intermittently depending on the patient’s response to either verbal or physical stimuli. 15 We believe that the combination of fentanyl bolus was a contributing factor for the decrease in oxygen saturation after the initiation of DEX.…”

The Adrenal Medulla Modulates Mechanical Allodynia in a Rat Model of Neuropathic Pain

“…Considering the ability of some PNMT inhibitors to interact with α2 adrenergic receptors [29] and the well-known antinociceptive and sedative effect of α2 adrenergic receptor agonists (e.g., dexmedetomidine, medetomidine, xylazine) [30], the effect of SKF29661 on mechanical allodynia was evaluated in rats treated with atipamezole (1 mg/kg, I.P. ), an antagonist of α2 adrenergic receptors [30].…”

“…Considering the ability of some PNMT inhibitors to interact with α2 adrenergic receptors [29] and the well-known antinociceptive and sedative effect of α2 adrenergic receptor agonists (e.g., dexmedetomidine, medetomidine, xylazine) [30], the effect of SKF29661 on mechanical allodynia was evaluated in rats treated with atipamezole (1 mg/kg, I.P. ), an antagonist of α2 adrenergic receptors [30]. Atipamezole, neither on its own nor in the presence of SKF29661, modified the PWT to mechanical stimulation in the CCI-injured hind paw, hence excluding a significant contribution of α2 adrenergic receptors to both neuropathic pain and the antiallodynic effect of SKF29661 (Figure 3).…”

“…This result was reproduced along the 4 days of SKF29661 treatment (data not shown), thereby excluding an effect of the PNMT inhibitor on motor-coordination that could influence nocifensive responses. Considering the ability of some PNMT inhibitors to interact with α2 adrenergic receptors [29] and the well-known antinociceptive and sedative effect of α2 adrenergic receptor agonists (e.g., dexmedetomidine, medetomidine, xylazine) [30], the effect of SKF29661 on mechanical allodynia was evaluated in rats treated with atipamezole (1 mg/kg, I.P. ), an antagonist of α2 adrenergic receptors [30].…”

Dexmedetomidine Inhibits ASIC Activity via Activation of α2A Adrenergic Receptors in Rat Dorsal Root Ganglion Neurons

“…Studies with α 2 -AR knock-out animal models suggest that α 2 -AR plays a major role in DEX analgesia (Hunter et al, 1997;Stone et al, 1997;Malmberg et al, 2001). In addition to neuropathic pain, studies have also confirmed that DEX has analgesic effects on pain under postoperative, acute and chronic inflammatory conditions (Mahmoud and Mason, 2015;Zhao et al, 2020). Clinically, DEX has been used to relieve acute postoperative pain, ischemic pain, refractory cancer pain (Hoy and Keating, 2011).…”