Satureja khuzestanica prevents the development of morphine analgesic tolerance through suppression of spinal glial cell activation in rats

Abstract

Glial cell activation and oxidative stress are important factors in the induction of opioid side effects such as tolerance and dependence. It has been demonstrated that Satureja khuzistanica extract (SKE) has antioxidative, antinociceptive and anti-inflammatory properties; however, its influences on opioid analgesic tolerance have not yet been clarified. Adult male Wistar rats were rendered analgesic-tolerant by injection of 10 mg/kg morphine twice daily for 8 days. To determine the effect of SKE on the development of morphine tolerance, different doses of SKE (25, 50 and 100 mg/kg i.p.) were injected simultaneously with morphine. The tail-flick test was used to assess the nociceptive threshold. The lumbar spinal cord was assayed to determine glial fibrillary acidic protein (GFAP) and tumor necrosis factor alpha (TNFα) levels by the Western blotting method. Our results showed that chronic morphine produced tolerance to the antinociceptive effect of morphine. However, SKE could prevent, in a dose-dependent manner, morphine tolerance development. In tolerant animals, a significant increase in GFAP and TNFα levels was observed in the lumbar spinal cord, and was reversed to control levels by 100 mg/kg SKE. Our data revealed that Satureja khuzistanica had beneficial effects in preventing opioid tolerance and the underlying mechanisms of those effects may be due, at least in part, to reduce spinal glial cell activation.

The anti-inflammatory properties of Satureja khuzistanica Jamzad essential oil attenuate the effects of traumatic brain injuries in rats

“…This may be due to a reduction in TNF-α production. Esmaili Mahani et al have shown that SKJ reduces TNF-α levels in rat spinal glial cells 51 .…”

The Antibacterial Activity of Satureja khuzestanica Essential Oil Against Clinical Isolates of E. coli

“…Recent studies have confirmed the anti-inflammatory (9), analgesic (10), and many traditional uses of this plant.…”

Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance

“…These changes are consistent with the small colloidal activation observed after neurite damage in the CNS. Glial cell activation and oxidative stress are important factors in inducing opioid side effects (e.g., tolerance and dependence) (Esmaeili-Mahani et al, 2015). CNS glial cells are non-neuronal cells that work with neurons to regulate the homeostasis of the nervous system, mediating and affecting pain.…”