Ex vivo characterization of joint innervating neurons in osteoarthritic rodent pain model
Nurmi, Venla-Mari (2023-08-28)
Ex vivo characterization of joint innervating neurons in osteoarthritic rodent pain model
(28.08.2023)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe20231124148964
https://urn.fi/URN:NBN:fi-fe20231124148964
Tiivistelmä
Osteoarthritis (OA) is the most common joint disease worldwide, affecting an estimate of 240 million people. The predominant symptom of OA is pain. Pain perception arises from nociceptive signals in the periphery, that travel through the afferent nerve fibres towards the central nervous system (CNS). The nerve fibres’ soma lies in the dorsal root ganglia (DRG), which are located alongside the spinal cord and the nerves project both to the periphery and to the CNS. Key nociceptors in the pain pathway are the transient receptor potential (TRP) channels and voltage-gated sodium (Navs) channels. TRP channels are associated with transducing noxious stimuli into an electrical signal in the periphery and Navs amplify these signals to reach the threshold for action potential generation.
This thesis project aimed to gain insight into joint pain in monoiodoacetate (MIA) induced OA in rats, as the identification of mechanisms of OA pain remains relevant since it could benefit the development of appropriate pain relief therapies for patients. The goal was to characterize changes that occur in DRG neurons from rats with OA pain, in acute and chronic phases. The research was performed by studying the protein expression of nociceptors, TRPC5 and NaV1.8, and assessing the excitability of DRG neurons using calcium imaging.
The protein expression of NaV1.8 in DRG does not appear to significantly change in MIA-induced OA pain with the settings in this study. However, the MIA model has increased TRPC5 expression from the acute to the chronic phase.
To measure the functional changes in DRG cells, spontaneous activity (SA), TRPV1 and TRPC4/5 stimulation were explored with calcium imaging. The percentage of SA cells decreases over time and there is a trend that cells from the MIA-treated animals are more SA on the first day compared to sham. Interestingly, there was no increase of TRPC4/5 stimulation in chronic MIA even though the expression of TRPC5 seems to be increased.
In conclusion, with this study design, despite that were no major differences in MIA-induced OA, pain tendencies observed in activity and expression warrant further investigations in rats. For example, it would be interesting to test the use of retrograde tracers to identify joint innervating neurons from DRG and study the possible changes specifically in these cells and to develop imaging analytical methods for in-depth protein expression analysis in DRG tissues.
This thesis project aimed to gain insight into joint pain in monoiodoacetate (MIA) induced OA in rats, as the identification of mechanisms of OA pain remains relevant since it could benefit the development of appropriate pain relief therapies for patients. The goal was to characterize changes that occur in DRG neurons from rats with OA pain, in acute and chronic phases. The research was performed by studying the protein expression of nociceptors, TRPC5 and NaV1.8, and assessing the excitability of DRG neurons using calcium imaging.
The protein expression of NaV1.8 in DRG does not appear to significantly change in MIA-induced OA pain with the settings in this study. However, the MIA model has increased TRPC5 expression from the acute to the chronic phase.
To measure the functional changes in DRG cells, spontaneous activity (SA), TRPV1 and TRPC4/5 stimulation were explored with calcium imaging. The percentage of SA cells decreases over time and there is a trend that cells from the MIA-treated animals are more SA on the first day compared to sham. Interestingly, there was no increase of TRPC4/5 stimulation in chronic MIA even though the expression of TRPC5 seems to be increased.
In conclusion, with this study design, despite that were no major differences in MIA-induced OA, pain tendencies observed in activity and expression warrant further investigations in rats. For example, it would be interesting to test the use of retrograde tracers to identify joint innervating neurons from DRG and study the possible changes specifically in these cells and to develop imaging analytical methods for in-depth protein expression analysis in DRG tissues.