Calcitonin gene‐related peptide in the joint: contributions to pain and inflammation

Abstract

Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated. Animal models of arthritis are revealing the molecular and pathophysiological events that accompany and lead to progression of both arthritis and pain. Peripheral actions of CGRP in the joint might contribute to both inflammation and joint afferent sensitization. CGRP and its specific receptors are expressed in joint afferents and up-regulated following arthritis induction. Peripheral CGRP release results in activation of synovial vascular cells, through which acute vasodilatation is followed by endothelial cell proliferation and angiogenesis, key features of chronic inflammation. Local administration of CGRP to the knee also increases mechanosensitivity of joint afferents, mimicking peripheral sensitization seen in arthritic joints. Increased mechanosensitivity in OA knees and pain behaviour can be reduced by peripherally acting CGRP receptor antagonists. Effects of CGRP pathway blockade on arthritic joint afferents, but not in normal joints, suggest contributions to sensitization rather than normal joint nociception. CGRP therefore might make key contributions to the transition from normal to persistent synovitis, and the progression from nociception to sensitization. Targeting CGRP or its receptors within joint tissues to prevent these undesirable transitions during early arthritis, or suppress them in established disease, might prevent persistent inflammation and relieve arthritis pain.

Is Helicobacter Pylori Associated with a Migraine?

“…The authors postulated a molecular link between these two conditions in the form of Calcitonin gene-related peptide "CGRP" which is released during migraine attacks and is potentially also involved in the pathogenesis of abdominal pain by causing inflammation of sensory GI neurons. Additionally, our results recovered relationship between migraine and joint pains, this could be interpreted in the light of the CGRP induced synovitis, where it was found that CGRP contributes to transition from normal to persistent synovitis, and the progression from nociception to sensitization [39]. Also, CGRP may play a role in pain transmission in somatic pain conditions such as joint and muscular chronic pain [40].…”

The Role of Peripheral Nociceptive Neurons in the Pathophysiology of Osteoarthritis Pain

“…Recent reviews have focused on the role of cytokines, neuropeptides, and cannabinoids in the development of peripheral sensitization in OA (38, 45, 46). Therefore, here we will focus on describing the potential role of NGF, sodium channels, and non-neuronal cells to peripheral sensitization in OA.…”

Upcoming value of gene expression analysis in rheumatology

“…Хроническая боль может быть следствием острой боли, обусловленной неадекватным процессом репарации, если вновь синтезированная функциональная ткань отличается по своему клеточному и матриксному составу от той, что предшествовала повреждению [53]. Другой тип хронической боли включает разобщение процессов генерации болевого сигнала и начального повреждения ткани (нейропатическая боль) [54].…”

“…Хроническое воспаление при РА приводит не только к фокальным эрозиям кости внутри воспаленных суставов, но и к генерализованному остеопорозу в аксиальном и апендикулярном скелете [108]. Кроме того, в отличие от острой фазы, хроническое воспаление часто связано с генерацией специфического иммунного ответа с одновременным повреждением ткани [53]. При этом, повреждение может прогрессировать, несмотря на отсутствие клинической активности (немое прогрессирование) [109] вследствие низкой чувствительности клинических методов оценки воспаления сустава, субклинического синовита или системных эффектов, вызванных активными процессами в других суставах [110].…”