Browsing by Subject "5HT2AR"

Neuropathic pain is a chronic pain condition, which affects the life quality of almost 10% of the adult population of Europe. Current treatments for neuropathic pain are either not effective enough or have severe adverse effects, which leads to an urgent need for novel and efficient treatment options. Serotonin receptors 5-HT2A have been shown to modulate GABAA receptor activity via KCC2 mediated pathways, which has been suggested to be a possible mechanism behind neuropathic pain. 5-HT2AR agonists LSD and psilocybin activate 5-HT2ARs and acts as a potential novel therapy for neuropathic pain. The aims of this study were to investigate whether 5-HT2AR agonists modulate mechanical allodynia in healthy mice and whether a single administration of 5-HT2AR agonists can reduce mechanical allodynia in mice after SNI. To see whether 5-HT2AR agonists induce mechanical allodynia in healthy mice, baseline response to mechanical stimulus was measured with von Frey filaments with different target forces (0.07 G, 0.16 G, 0.4 G, 0.6 G and 1 G). Mice were treated with LSD, psilocybin, or saline, and after 5 minutes, the von Frey measurements were taken again. The allodynia was induced with SNI, where the common peroneal nerve and tibial nerve were ligated and cut, leaving the sural nerve intact. The development of mechanical allodynia was measured with von Frey filaments before the surgery and on post-operative day 14. On post-operative day 14, after the von Frey measurements, the mice were injected with LSD, psilocybin, pregabalin or saline. After 5 min, post-treatment measurements were performed. The experiments showed that 5-HT2AR agonists do not modulate mechanical allodynia in healthy mice. In SNI mice, psilocybin showed reduced mechanical allodynia between pre- and post-treatment measurements in 0.6 G and in 1 G, while LSD in 0.6 G. When comparing the average effects of 5-HT2AR agonists to allodynia and pain, psilocybin reduced the mechanical allodynia and pain, while LSD only had an effect on pain. The results suggest that 5-HT2AR agonists have analgesic effects after single administration in mice. Overall, this thesis provides insight into the therapeutic potential of 5-HT2AR agonists in the treatment of neuropathic pain and provides interesting viewpoints for the future research in the field.