TRP channel control of pain and analgesia

The available treatments of chronic pain are either associated with low efficacy on patients or with undesirable side effects. Several members of the TRP channel family of ion channels have been major targets for the development of novel analgesic drugs. The ion channel TRPA1, controls pain and nociception through an indirect mechanism.Transgenic mice lacking TRPA1 have a profound loss of mechanical sensitivity and a significantly reduced behavioural sensitivity to cold stimulation.Our most recent results show that the loss of pain and sensitivity in neuropathic models is not directly related to TRPA1. Instead, an endogenous analgesic receptor system is engaged in the absence of TRPA1 and interventions that inhibit this signalling pathway normalize sensory function and pain, in TRPA1 knockout mice.

Despite the fact that TRPA1 has been extensively studied, the channel's expression pattern in a variety of neuronal tissues has not been verified yet. This is the case, because the available commercial antibodies are not target specific. As a result, the vast majority of expression studies regarding TRPA1 are not supported by RNA sequencing data. Additionally, TRPA1 interacts with a variety of other molecules, the expression of which has not been studied in relation to TRPA1. Our aim is to determine the expression pattern of TRPA1 and other molecules in peripheral neuronal tissue, using in situ hybridization. This technique was selected because of its high specificity. However, not only is it important to determine the expression pattern of the channel and other receptors of interest, but also to reveal their interactions. For this reason, cells were transfected with the receptors, and the highest expressing clones were selected. The purpose of a stable cell line creation is to characterise pharmacologically the interactions between the molecules of interest, using a variety of assays.