**1. Introduction**

Low back pain (LBP) is the leading cause of disability, activity limitation and lost productivity throughout the world today, with approximately 80% of all people suffering from back pain at least once in their life [1]. Degenerative disc disease (DDD), which is a progressive multifactorial disorder of the intervertebral disc (IVD), is an important factor that is involved in the development of LBP [1]. DDD is characterized by the release of inflammatory and catabolic mediators, including interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), prostaglandins, and proteases, which further promote the degradation of extracellular matrix (ECM) [2,3]. Pro-inflammatory cytokines IL-1β and TNF-α directly act as nociceptive triggers, but also activate the expression of other potentially nociceptive molecules including neuropeptides, interleukin-6 (IL-6), and interleukin-8 (IL-8) [4,5]. Molecular mechanisms involved in transduction and modulation of IL-1β and TNF-α signaling in DDD are not yet well-understood [6–8].

Signals that are provided by pro-inflammatory cytokines can be mediated via membrane channels [9,10]. Recently, transient receptor potential (TRP) channels have emerged as putative receptors for inflammation-associated molecules, positive/negative regulators of inflammation, and transducers of inflammatory pain [11–13]. TRP channels are cation selective transmembrane receptors with diverse physiological functions. Six families of mammalian TRP channels have been identified, classifying TRP channels according to their sequence homology and topological differences: TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPV (vanillin), TRPP (polycystin), and TRPML (mucolipin). Apart from TRPA, every subfamily has several members [14,15]. The dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies, and hyperalgesia [14,16]. Interestingly, the expression and activity of certain TRP channels is altered in painful joints and IVDs [11,12]. For example, the expression of TRPV4 in human IVDs was found to be elevated in regions of aggrecan depletion [17], while the gene expression of TRPC6 was associated with the severity of disc degeneration, increased expression of IL-6, and cell senescence [18,19]. TRPA1 and TRPV1 are involved in inflammation/nociception in sensory neurons and non-neuronal tissues [20–22]. TRPV1 is a non-selective calcium channel, the expression and activity of which increases after inflammatory stimulation in dorsal root ganglions (DRGs), possibly causing chronic hyperalgesia. TRPV1 also expressed in chondrocytes [23]. TRPA1 is a calcium permeable non-selective cation channel that is also widely expressed in sensory neurons and in non-neuronal cells, including chondrocytes [11]. TRPA1 is involved in various sensory and homeostatic functions, depending on the cell type [12,24]. TRPA1 and TRPV1 were shown to complement each other's activities [21,25]. As numerous publications have linked TRPA1 and TRPV1 with inflammatory pain [21], therapeutic inhibition or the activation of TRPA1 and/or TRPV1 channels may be beneficial in the treatment of DDD. Therefore, the aims of this study were to investigate the (1) expression of TRP channels in IVD cells in normal and inflammatory conditions and (2) the function of TRPA1 and TRPV1 in disc inflammation and matrix homeostasis.
