Antinociception by Epidural and Systemic α2-Adrenoceptor Agonists and Their Binding Affinity in Rat Spinal Cord and Brain

Abstract

Spinal antinociception caused by the epidural administration of alpha(2) agonists is well correlated with their binding affinity to spinal alpha(2)-adrenoceptors.

Addition of epidural Clonidine enhances postoperative analgesia: A double-blind study in total knee- replacement surgeries

“…Several studies have been published in the last decades describing the anesthetic sparing effects and analgesic property of epidural clonidine. [1–3] Clonidine, a a-2 agonist agent, is causing analgesia with a non-Opioid mechanism as an alternative agent to Opioid. [13–15] It was stated that clonidine neither affects proprioception like local anesthetics nor causes respiratory depression, itching, nausea and vomiting like Opioids, but When given by epidural route with local anesthetics, it increase analgesia potency.…”

“…Noradrenergic ganglions in pons and medulla can not be activated by Opioid or noxious stimulus that causes nor epinephrine secretion at dorsal horn of spinal cord. [23] When molecular weight, lipid solubility and cerebrospinal fluid pharmacokinetics of clonidine are taken into consideration, start of its analgesic effect and duration of analgesia can be expected to be similar to Fentanyl but analgesic effect of Fentanyl starts faster and lasts longer. [1617]…”

A comparative study of the effect of caudal dexmedetomidine versus morphine added to bupivacaine in pediatric infra-umbilical surgery

“…[5] Dexmedetomidine has, as much as, eight folds more stronger affinity to α2 adrenergic receptors and lower affinity to α1 receptors than clonidine, besides its great advantage in having higher selectivity to α 2A adrenergic receptors, responsible for the analgesic effect of such drugs, compared with clonidine. [6]…”

Involvement of Protein Kinase B/Akt in Analgesic Effect of Dexmedetomidine on Neuropathic Pain

“…Dexmedetomidine, a highly selective alpha 2 -adrenoceptor (a 2 -AR) agonist, has been used in human as a medication for analgesia, sedation in the intensive care unit (ICU), and an adjunct for anesthesia [2]. It has been shown that dexmedetomidine can stimulate a 2 -ARs in the spinal cord to enhance analgesia [3]. There are three a 2 -AR subtypes, a 2A , a 2B , and a 2C .…”

“…However, it has been assessed that a 2A -AR is the predominant subtype involved in the mediation of the antinociceptive action of dexmedetomidine [4]. Increasing evidence demonstrates that systemic or intrathecal application of dexmedetomidine produces significant antinociceptive effects in various rodent models of chronic pain [3,5]. However, the signaling pathway involved in the analgesic effect of dexmedetomidine remains unclear.…”