Joint nociceptor nerve activity and pain in an animal model of acute gout and its modulation by intra-articular hyaluronan.

The mechanisms whereby deposition of monosodium urate (MSU) crystals in gout activates nociceptors to induce joint pain are incompletely understood. We tried to reproduce the signs of painful gouty arthritis, injecting into the knee joint of rats suspensions containing amorphous or triclinic, needle MSU crystals. The magnitude of MSU-induced inflammation and pain behavior signs were correlated with the changes in firing frequency of spontaneous and movement-evoked nerve impulse activity recorded in single knee joint nociceptor saphenous nerve fibers. Joint swelling, mechanical and cold allodynia, and hyperalgesia appeared 3 hours after joint injection of MSU crystals. In parallel, spontaneous and movement-evoked joint nociceptor impulse activity raised significantly. Solutions containing amorphous or needle-shaped MSU crystals had similar inflammatory and electrophysiological effects. Intra-articular injection of hyaluronan (HA, Synvisc), a high-MW glycosaminoglycan present in the synovial fluid with analgesic effects in osteoarthritis, significantly reduced MSU-induced behavioral signs of pain and decreased the enhanced joint nociceptor activity. Our results support the interpretation that pain and nociceptor activation are not triggered by direct mechanical stimulation of nociceptors by MSU crystals, but are primarily caused by the release of excitatory mediators by inflammatory cells activated by MSU crystals. Intra-articular HA decreased behavioral and electrophysiological signs of pain, possibly through its viscoelastic filtering effect on the mechanical forces acting over sensitized joint sensory endings and probably also by a direct interaction of HA molecules with the transducing channels expressed in joint nociceptor terminals.

Current advances in therapies for calcium pyrophosphate crystal arthritis.

PURPOSE OF REVIEW: Calcium pyrophosphate (CPP) crystal disease is a common rheumatologic disorder that has received limited attention from the scientific community. This review is aimed at summarizing current evidence for managing CPP disease (CPPD), focusing on recently reported advances. RECENT FINDINGS: New data from case series indicate that interleukin-1ß inhibitors can help patients with refractory forms of CPPD. Methotrexate, formerly a promising agent, failed to demonstrate benefits in a recent trial, but still merits consideration for some patients. No significant advances on crystal dissolution have been achieved to date. Proper characterization of the CPP crystal disease picture is needed, ruling out the possible coexistence of another persistent arthritis unrelated to the CPP deposition. SUMMARY: Advances on CPP crystal dissolution and establishing definitions of the clinical spectrum of CPPD remain the main challenges for CPP crystal disease management.