Speaker Biography

Nana Tsiklauri
Biography:

Abstract:

Introduction.  Rheumatoid arthritis (RA) is the chronic (long-term) disease, that cause pain and limited motion and function of many joints. It has been discovered that cannabinoid  receptors are expressed  in the amygdala, and their activity contributes to the dissociative effect of cannabis on pain perception. It has been also shown  In our investigations, that repeated microinjection of NSAIDs into central nucleus of amygdala induces development of tolerance to them. Therefore very interesting to figure out if repeated microinjections of cannabinoids into  the central nucleus of amygdale could   induce tolerance effects to them. There are many studies examining the effects of  cannabinoids   in  relief   of acute and    chronic inflammatory pain, and many researches  try  to prove high efficiency  and  demonstrate new capabilities  of  these drugs in rheumatoid  arthritis treatment.  But much less is known about their side effects like tolerance after repeated administration for long-term treatment. Therefore we  studied the antinociception and tolerance during chronic pain in rheumatoid arthritis induced by administration of delta-9-  tetrahydrocannabinol (Δ9-THC) into the central nucleus of amigdala for five consecutive days.

Methods. We Induced rheumatoid arthritis in rats by immunization, with an emulsion of complete Freund,s adjuvant and type II collagen (CII), into the tail and  monitored of arthritis incidence during 5-8 weeks. :  After  developing  arthritis  incidence, surgical procedures for streotaxically  bilaterally inplant cannulas into central nucleus of amygdala(CeA) . Repeated  microinjections by  Δ9‐THC During five   consecutive  days, one   times in day and then testing antinociception using the tail-flick (TF) reflex and  on the latency of thermal paw withdrawal reflex and mechanical threshold of paw withdrawal.          

Results. Microinjection of Δ9‐THC into the central nucleus of amygdala produced antinociception, as detected by increased latencies in the TF and thermal paw and mechanical paw withdrawal threshold   tests as compared to the baseline and to the control group that received saline microinjections in CeA.

On subsequent days Δ9‐THC microinjections caused progressively less antinociception i.e., (tolerance), so that by day 5 there was no effect (i.e., injected groups on day 5 were not significantly different from saline microinjections in all tests).

Conclusions. Here we demonstrated that microinjection of Δ9‐THC, injected into the central nucleus of amygdala, induced antinociception in rheumatoid arthritis model of rats and repeated administration of cannabis induced development of tolerance to them.

In this work we have shown that a long-term use of cannabinoids cause development of tolerance toward them, so this is one of the side effects of cannabinoids, and using for treatment these drugs  in rheumatoid arthritis is  limited.

Acknowlegement. This research was supported by the grant from Shota Rustaveli National Science Foundation of Georgia (YS17-53).