Full Length Article Histopathological analysis of the synovium in trapeziometacarpal osteoarthritis Susanne Rein 1 , Janet Okogbaa 2 , Elisabet Hagert 3 , Suzanne Manthey 4 and Amy Ladd 2 Abstract Dorsoradial and anterior oblique ligaments were harvested during surgery in 13 patients with symptomatic trapeziometacarpal osteoarthritis, which had been graded preoperatively by a modified Eaton-Littler radiographic grading. Ligaments, including the periligamentous synovium, were stained with S100 protein, neurotrophic receptor p75, protein gene product 9.5, calcitonin gene related peptide, acetylcholine, substance P, neuropeptide Y, noradrenaline, N-methyl-D-aspartate-receptor and Met/Leu-enkephalin. The synovium was classified as showing no, low-grade or high-grade synovitis. Free nerve endings had higher immunoreactivity for substance P than for N-methyl-D-aspartate-receptor, enkephalin and noradrenaline. The synovial stroma had less immunoreactivity for N-methyl-D-aspartate-receptor than for noradrenaline, substance P and calcitonin gene related peptide. There was no relation between the grade of osteoarthritis and the visual pain analogue scale, synovitis score, immunoreactivity of all antibodies and quantity of free nerve endings or blood vessels. Synovium in trapeziometacarpal joint osteoarthritis produces several neuromediators causing a polymodal neurogenic inflammation and which may serve as biomarkers for osteoarthritis or therapeutic targets. Keywords Basal thumb joint, immunohistochemistry, nociception, osteoarthritis, synovium Date received: 19th November 2018; revised: 13th April 2019; accepted: 15th April 2019 Introduction Trapeziometacarpal joint osteoarthritis (TMJOA) affects the joint cartilage as well as the supporting soft tissues of the joint. The presence of synovitis in osteoarthritis (OA) is associated with more severe pain and joint dysfunction. The thin layer of synovial cells and the underlying vascularized connective tissue stroma provide structures and fluid essential for normal cartilage and joint function (Scanzello and Goldring, 2012). Synovial lining cells, lubricin and hyaluronic acid help to protect and maintain the integrity of articular cartilage surfaces in joints. Synovitis in OA is deemed to be a secondary reaction to cartilage fragments and debris. The nervous system plays an active role in regu- lating pain and inflammation (Yam et al., 2018). Neurogenic inflammation refers to the inflammation that is produced through the release of mediators, such as substance P (SP) and calcitonin gene-related reptide (CGRP), from the nervous system. It involves a change in function of sensory neurons due to inflammatory mediators, inducing an enhanced release of neuropeptides from the sensory nerve endings. Polymodal nociceptors – encoding and pro- cessing harmful stimuli – serve to protect the body from potential harm, reacting to noxious thermal, mechanical or chemical stimuli, tissue damage and 1 Department of Plastic and Hand Surgery, Burn Unit, Hospital Sankt Georg, Leipzig, Germany 2 Department of Orthopaedic Surgery, Chase Hand Center, Stanford University, Stanford, CA, USA 3 Department of Clinical Science and Education, Karolinska Institutet, Arcademy, H. M. Queen Sophia Hospital, Stockholm, Sweden 4 University Center of Orthopaedics and Traumatology, University Medicine Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany Corresponding Author: Susanne Rein, Department of Plastic and Hand Surgery, Burn Unit, Hospital Sankt Georg, Delitzscher Straße 141, 04129 Leipzig, Germany. Email: susanne.rein@web.de Journal of Hand Surgery (European Volume) 0(0) 1–10 ! The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1753193419848600 journals.sagepub.com/home/jhs