Comparative investigation of analgesic tolerance to taurine, sodium salicylate and morphine: Involvement of peripheral muscarinic receptors

Nowadays various analgesic medications are used for the management of acute and chronic pain. Among these opioid and non-steroidal anti-inflammatory drugs stand in the first line of therapy, however, prolonged administration of these substance is generally challenged by development of analgesic tolerance in patients. Therefore, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. In this respect, Taurine, a free amino acid, has been shown to induce significant analgesia at both spinal and pe-ripheral levels through cholinergic mechanisms. In the present study, we used hot-plate analgesic test to investigate how taurine either as a single medication or in combination with sodium salicylate and morphine may affect both acute response to pain and development of analgesic tolerance. The effect of taurine was also tested on morphine withdrawal syndrome. Hyoscine butyl bromide was used to assess the role of muscarinic receptors in taurine-mediated effects. Finally, biochemical assay was done to reveal how the activity of brain acetylcholinesterase may change in relation with muscarinic receptor activity. Results indicated that acute administration of taurine-sodium salicylate combination causes more potent analgesia compared to the use of tau (but not SS alone) and this seems to be mediated via activity of muscarinic receptors in peripheral nervous system. Furthermore, the effect of this combination undergoes less analgesic tolerance during time. Combination of taurine and morphine is an effective strategy to attenuate both morphine analgesic tolerance and dependence and this also seems to depend on activity of muscarinic receptors, however through differential cellular mechanisms.

Automated summary

Various analgesic medications, including opioids and non-steroidal anti-inflammatory drugs, are commonly used for pain management. However, prolonged administration of these drugs often leads to the development of analgesic tolerance. This study investigates the analgesic effects of taurine alone or in combination with sodium salicylate or morphine, and also explores the role of muscarinic receptors in these effects. The results suggest that the combination of taurine and sodium salicylate has a more potent analgesic effect and less tolerance development compared to taurine alone.