TRPC5 in the context of neuropathic and inflammatory pain

Background & Aims
Chronic pain is a major health problem affecting 10-20% of the population worldwide. Because of unsatisfactory treatments with harsh side effects - especially for neuropathic pain patients - there is an emerging need for novel and innovative approaches. In context of different pain states, it is well known that TRP-channel superfamily contributes to pain hypersensitivity by sensitising pain relevant neurons. Unfortunately, they are in general too important for physiological sensations, which makes it difficult to target them. Because of this we want to focus on proteins that are not responsible for normal tactile pain and pain sensations but are upregulated in pathophysiological pain states respectively. Therefore, the transient receptor potential canonical channel 5 (TRPC5) was identified as potential candidate. To understand the responsibilities and the role in the development of pain we set our focus to TRPC5 in this study. TRPC5 is one of the seven mammalian TRPC proteins. Functionally, it is a non-selective calcium permeable cation channel which acts as homotetrameric or heteromultimeric assemblies with other TRPC proteins.   

Results
In our study we first investigated the expression of TRPC5 target mRNA and protein levels in different pain relevant tissues of the treated animals. After triggering a chemotherapy induced peripheral neuropathy (CIPN) in vivo, we observed a significant increase in the expression of TRPC5 in neuronal tissue.
Based on these results, we aimed to gain a deeper understanding of the role of TRPC5 in the development of neuropathic pain. Therefore, we first investigated the influence of different already known inhibitory modulators (AC1903, HC 070) of the channel in our cell system and confirmed earlier findings. Additionally, we screened several lipids to examine their interaction with the receptor. Our findings show that special lysophospholipids and eicosanoids can modulate the activity of the TRPC5 channel. We plan to further investigate these compounds on primary cell cultures from mice and their relevance in persistent pain states in vivo.