Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

Abstract

Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days-(1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

“…No change was observed in the thalamus of the two groups of macaques. These findings are in keeping with the previous reports wherein morphine administered rats exhibited neuroinflammation in the cortex [84,85], nucleus accumbens [86], ventral tegmental area [87], and cerebellum [85], and decreased expression of proinflammatory cytokines in the rat hippocampus [88], and brain stem [86]. Interestingly, morphine-dependent animals exhibited increased proinflammatory cytokines expression in brain regions (frontal cortex, occipital cortex, cerebellum and basal ganglia) where the ER stress-mediated defective autophagy was predominant.…”

Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis

“…Further, GFAP expression is increased in the locus coeruleus (LC) and nucleus of the solitary tract (NST) after chronic morphine treatment [278]. Further still, one day following chronic morphine treatment, GFAP expression is increased in the NAc, but decreased in the mesencephalon [279]. Lastly, morphine induced conditioned place preference (CPP) elicits dynamic changes in GFAP expression in the amygdala, as GFAP is reduced following extinction of morphine CPP but not after morphine-induced reinstatement to CPP [280].…”