S-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats

Neurosci Lett. 2017 Apr 3:645:67-73. doi: 10.1016/j.neulet.2017.02.054. Epub 2017 Feb 22.

Abstract

Background: Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance.

Methods: Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i.p.), once daily for 5days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800mg/kg was administered orally (p.o.), 45min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated.

Results: Co-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration.

Conclusion: Since safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated.

Keywords: Morphine; Pain; S-adenosylmethionine (SAM); Tail flick latency; Tolerance.

MeSH terms

  • Animals
  • Drug Tolerance
  • Male
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology*
  • Rats, Wistar
  • Reaction Time
  • S-Adenosylmethionine / pharmacology*
  • Tail

Substances

  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Morphine
  • S-Adenosylmethionine