Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice

Abstract

Background The most important limitations of morphine in pain therapy are its tolerance and dependence. In this study, we evaluated the protective effect of glucosamine against morphine-induced tolerance and dependence in mice. Methods Mice received twice daily morphine (20 mg/kg, s.c.) alone, or along with orally administered glucosamine (500, 1000 and 2000 mg/kg), for 9 continuous days. To assess antinociceptive effect of morphine, percentage of maximal possible effect (%MPE) of animals exposed to thermal stimulus was measured in the hot plate test, 30 min after morphine administration. Test was performed on days 1, 3, 5, 7 and 9. The effect of glucosamine on the naloxone (5 mg/kg, i.p.)-precipitated morphine withdrawal, was also evaluated. Changes in brain gene expression levels of induced nitric oxide synthase (iNOS), enzyme responsible for nitric oxide generation, as well as pro-inflammatory mediator, tumor necrosis alpha (TNF-α) were measured in morphine tolerated animals, as well as after withdrawal by real-time polymerase chain reaction (RT-PCR). Protein content of TNF-α was evaluated via ELISA assay. Results Tolerance to antinociceptive effect of morphine was developed after 7 days of morphine treatment. The concurrent administration of glucosamine (500, 1000 and 2000 mg/kg) with morphine, significantly inhibited tolerance development, on days 7 and 9. In addition, glucosamine ameliorated the naloxone-precipitated opioid withdrawal symptoms (tremor, jumping, teeth chattering, grooming). However, diarrhea was significantly improved only with the dose of 500 mg/kg. Increased mRNA expression of iNOS as well as TNF-α mRNA expression and protein, after both morphine tolerance and withdrawal, were considerably reduced by glucosamine (1000 mg/kg) in the morphine withdrawal animals. Conclusion These data support the utility of glucosamine in attenuating both tolerance to nociceptive effects of morphine as well as withdrawal-induced behavioral profile. Anti-oxidant and anti-inflammatory effects are responsible, at least in part, for the protective effects of this drug.

Beneficial Effects of Some Nutraceuticals Containing Glucosamine and Antioxidant against CCL4 Induced Brain Injury in Rats

“…The anti-inflammatory effects of GlcN were mainly attributable to its ability to inhibit nuclear factor kappaB (NF-κB) activation (Hwang et al [8]). Glucosamine itself will help manage the stress response and reduce the amount of inflammation and thereby help in limiting the amount of tissue damage (Syed et al [50] and Faezeh et al [51]). The study of Chen et al [52] supports the previous results, findings that GlcN protected retinal ganglion cells (RGCs) from oxidative stress-induced injury via the modulation of protein O-GlcNAc glycosylation.…”

Assessment of Toxicity and Biological Effects of α-Pinene on Morphine Tolerance and Dependence in Mice

“…Dependence on opioids (e.g., morphine) is a serious disease that causes enormous health problems and economic losses for individuals and societies (1). Morphine, which is used to relieve acute and chronic pain, promotes its analgesic effects through the modulation of µ opioid receptors (2). However, the continuous use of morphine leads to euphoria, respiratory depression, constipation, miosis, tolerance, and dependence, limiting its clinical use (3).…”