Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10 −7 ng/mL) and joints with pathology (12.9 × 10 −7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation.Animals 2020, 10, 506 2 of 15 described aetiology is trauma-either as a single event or as a series of microtrauma. This will induce an inflammatory response, which, in turn, will drive the process of articular cartilage breakdown and remodelling of the surrounding bone [4]. Consequently, horses diagnosed with OA are often retired or euthanised.There is a broad spectrum of treatments for equine OA. Most of them are anti-inflammatory and pain-relieving without a true disease-modifying effect, although regenerative medicine in regard to equine OA is a rapidly evolving area [5][6][7][8]. Two of the drug groups most commonly used for treating the symptoms related to equine OA are nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroids, often in combination. NSAIDs are predisposing for gastrointestinal ulceration and are potentially nephrotoxic, and corticosteroids are potentially chondrotoxic [9][10][11][12]. In human medicine, so-called disease-modifying osteoarthritis drugs (DMOADs) are being investigated in an attempt to stop the disease progression, as well as being pain-relieving and anti-inflammatory. However, an effective disease-modifying drug has not yet been developed [13].Several authors point to the ...