Oxycodone ameliorates the inflammatory response induced by lipopolysaccharide in primary microglia

Abstract

BackgroundActivation of microglia participates in a wide range of pathophysiological processes in the central nervous system. Some studies reported that oxycodone (6-deoxy-7,8-dehydro-14-hydroxy-3-O-methyl-6oxomorphine) could inhibit the overactivation of glial cells in rats’ spinal cords. In the present study, we observed the effect of oxycodone on inflammatory molecules and pathway in lipopolysaccharide (LPS)-stimulated primary microglia in rats.Materials and methodsNeonatal rats’ primary microglia were exposed to various concentrations (25, 50, 100 ng/mL) of oxycodone for 1 h after LPS stimulation for 24 h. The levels of pro-inflammatory mediators, IL-1β, TNF-α, and TGF-β1/smad2/3 signaling pathway were measured. The activation situation of microglia and the expression of TβR1 were observed by immunofluorescence.ResultsOxycodone at 25 ng/mL did not change the levels of proinflammatory molecules and TGF-β1/smad2/3 signaling pathway in primary microglia, which was increased by LPS. Oxycodone at 50 and 100 ng/mL could significantly suppress LPS-induced production of TNF-α and IL-1β and the expression of TNF-αmRNA, IL-1βmRNA, and TGF-β1/smad2/3 signaling pathway.ConclusionThese findings indicate that oxycodone, at relatively high clinically relevant concentration, can inhibit inflammatory response in LPS-induced primary microglia. The detailed mechanism needs to be investigated in future.

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis

“…Oxycodone is a widely used analgesic due to its several advantages. Except for μ and κ receptor activation, the attenuation of the inflammatory response in microglia and the regulation of GABAB receptor are also involved in the analgesic effect of oxycodone, especially for chemotherapy-induced neuropathic pain [23, 24]. In our study, we demonstrated that oxycodone can inhibit the inflammation in the primary microglia induced by vincristine, which may be related to the reduction of CXCL10 and CXCL9 expression.…”

A Bibliometric Analysis of Publications on Oxycodone from 1998 to 2017

“…Walentiny et.al found that nociceptin/orphanin FQ (NOP) receptor activation can modulate the discriminative stimulus effects of oxycodone in C57BL/6 mice [12]. In vivo and vitro, some results of researches also demonstrated that oxycodone could decrease spinal nerve injury (SNL)-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α) [13, 14]. In consideration of opioids-drugs abuse, Zhang et al found several alterations of expression of genes related to inflammation/immune functions in the dorsal striatum of adult C57BL/6J mice following chronic oxycodone self-administration, which revealed some novel neurobiological underlying mechanisms of abused prescription opioid [15].…”

Protective Effects of Dexmedetomidine and Oxycodone in Patients Undergoing Limb Ischemia-Reperfusion

“…These unexpected findings suggest that treatment with Oxy may increases risk of cognitive complications. Several studies suggested that Oxy can relieve the inflammatory response [12,13], so we hypothesized that Oxy could reduce inflammatory reaction and improve postoperative cognitive function. However, our study data contradict this hypothesis.…”

“…Oxycodone (Oxy), a μ and κ opioid receptor agonist, is increasingly used worldwide to treat a variety of painful disorders [11]. Recently, several studies suggested that Oxy not only provides potent analgesia but also relieves the inflammatory response [12,13]. To date, no study has investigated the anti-inflammatory effects of Oxy in patients undergoing limb ischemia-reperfusion.…”