Amino acid release into the knee joint: key role in nociception and inflammation

Abstract

This study examined the release of several amino acids after induction of knee joint inflammation in rats using kaolin and carrageenan. During the initial 10-min collection after knee joint injection with the irritants, the concentration of glutamate and the nitric oxide metabolites, arginine and citrulline, doubled. This increase persisted for at least two hours. During the same time period aspartate concentrations remained unchanged. Direct knee joint administration of lidocaine prevented the increases in amino acid concentration measurable by microdialysis probe inserted into the joint. These data suggest the possibility that glutamate may be released by neuronal endings in the joint.

Activin Induces Tactile Allodynia and Increases Calcitonin Gene-Related Peptide after Peripheral Inflammation

“…Peripheral nerves release transmitters and peptides, including CGRP (Lam and Ferrell, 1991;Mulder et al, 1997;Lawand et al, 2000). Unilateral inflammation causes alterations in nociceptive thresholds (Stein et al, 1988), and notably, mice deficient in the ␣-CGRP gene fail to develop secondary hyperalgesia after inflammation (Zhang et al, 2001).…”

Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament‐transected knee: Association with excitatory amino acid release in the joint dialysate

“…41 Intraarticular EAA injection resulted in thermal hyperalgesia and mechanical allodynia, which were attenuated by local injection of N-methyl-D-aspartate (NMDA) or non-NMDA receptor antagonists. 27 Lawand et al 26 also demonstrated that intraarticular lidocaine injection prevented glutamate release and nociceptors sensitization of inflammatory joints. Moreover, in inflamed arthritic knees, an increase of glutamate concentration was observed not only in the axons in the inflamed region, 25 but also in the synovial fluid.…”

“…A 27-gauge needle attached to a tuberculin syringe was passed through the joint capsule lateral to the patellar ligament, then the microdialysis probe was inserted through the needle into the knee joint, following the protocol described by Lawand et al, 26 and its position confirmed by X-ray examination. The microdialysis probe 28 was constructed using two 5-cm polyethylene tubes (0.008-inch inner diameter, 0.014-inch outer diameter) and a 1.5-cm cuprophan hollow fiber (300 mm outer diameter, 200 mm inner diameter, 50 kDa molecular weight cutoff; Filtral, AN 69-HF, Eicom Co., Kyoto, Japan).…”

“…25 A potential peripheral action of glutamate has been suggested, as increased glutamate levels are seen in the peripheral tissues in acute and chronic inflammation in both animals and humans. 23,26,27 Increased glutamate levels in the knee joint and medial articular nerve are seen after induction of arthritis in the rat. 26 We previously reported that glutamate and aspartate levels were significantly increased in dialysates of anterior cruciate ligament-transected (ACLT) knees, 28 suggesting a role of EAA in early OA development.…”

“…23,26,27 Increased glutamate levels in the knee joint and medial articular nerve are seen after induction of arthritis in the rat. 26 We previously reported that glutamate and aspartate levels were significantly increased in dialysates of anterior cruciate ligament-transected (ACLT) knees, 28 suggesting a role of EAA in early OA development. Glutamate transporters have been identified in bone, 29 raising the possibility that EAA participate in signal transduction between bone cells.…”