Molecular mechanisms of pain in crystal-induced arthritis.
Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1β), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1β agents, should be used only in particularly refractory cases.
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: Roberta.ramonda@unipd.it.
R
R
Ramonda
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: Francesca.oliviero@unipd.it.
F
F
Oliviero
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: paola.galozzi@unipd.it.
P
P
Galozzi
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: paola.frallonardo@unipd.it.
P
P
Frallonardo
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: mariagrazialorenzin@libero.it.
M
M
Lorenzin
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: augusta.ortolan@yahoo.it.
A
A
Ortolan
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: anna.scanu@unipd.it.
A
A
Scanu
Rheumatology Unit, Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: punzireu@unipd.it.
L
L
Punzi
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002131:Calcium Pyrophosphate; D002805:Chondrocalcinosis / Q000150:complications*; D006073:Gout / Q000150:complications*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy / Q000209:etiology*; D014527:Uric Acid
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014527:Uric Acid; D002131:Calcium Pyrophosphate
Basic calcium phosphate crystals; Colchicine; Crystal-induced arthritis; Interleukin-1β; Kinin system; Monosodium urate crystals; NSAIDs; Pain; Prostaglandins; Pyrophosphate crystals