Neural changes in acute arthritis in monkeys. II. Increased glutamate immunoreactivity in the medial articular nerve

Glutamate and other excitatory amino acids have been shown to play a key role in nociception and the hyperalgesia associated with the acute inflammatory response. In an effort to understand more fully the role of Glu in this process, we determined that there is Glu in a percentage of axons in the medial articular nerve (MAN) of monkeys, a source of preterminal afferent fibers innervating the knee joint. After induction of the experimental knee joint inflammation with a kaolin/carrageenan mixture, comparison was made of the percentage of Glu positive axons in the MAN on the side of the inflammation versus the contralateral MAN using post-embedding immunogold electron microscopic methods. A doubling in the percentage of Glu-containing axons was observed on the side of the experimental arthritis as compared to the MAN of the other side or of uninjected controls. Glu positive axons were unmyelinated or were included in the small, thinly myelinated group in control nerves. Following induction of the inflammation, axonal diameter measurements revealed an increase in Glu content primarily in the small, thinly myelinated axons, which correspond to the group III afferent fibers. These increases were observed in the anesthetized preparation only when injection of kaolin/carrageenan was combined with joint flexion and mechanical stimulation. The dramatic increase in percentages of fibers stainable for Glu in the MAN following the induction of inflammation suggests that Glu content is greatly increased in the afferent fibers and may be a major contributor to the enhanced responses of sensory neurons in inflammatory states such as arthritis.