Abstract
BackgroundThe 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.MethodsMice 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.ResultsTolerance 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.ConclusionThese 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.
Highlights
Opioids including morphine have been used to relief acute and chronic kinds of pain, and rank among the most powerful analgesic drugs
Effect of glucosamine on the development of morphine tolerance It should be noted that glucosamine alone (1000 mg/kg) treated mice didn’t show a significant difference with normal saline control ones, indicating no significant analgesic effect
Our results showed that the mRNA expression of induced nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), as well as its protein content increased both in tolerated animals and after naloxone challenge in mice treated with 9 days morphine
Summary
Opioids (narcotics) including morphine have been used to relief acute and chronic kinds of pain, and rank among the most powerful analgesic drugs. Side effects especially tolerance to analgesic effects in patients chronically treaded with such drugs, are common [1, 2]. Another problem by opioids is physical dependence with withdrawal avoidance behaviors, limiting their therapeutic utility in clinic. This situation occurs when opioids are suddenly ceased or an antagonist is taken by patients. We evaluated the protective effect of glucosamine against morphine-induced tolerance and dependence in mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
