Is large myelinated fiber loss associated with hyperalgesia in a model of experimental peripheral neuropathy in the rat?

Recently it has been shown that placement of 4 loose chromic gut sutures around the rat sciatic nerve produces hyperalgesia. A possible mechanism underlying this hyperalgesia is a preferential loss of large myelinated fibers. A difficulty, however, is that neuropathic symptoms are not static and the time course of the axon loss has not been determined. To remedy this deficit, the present study relates axonal changes to the behavior of the animal at various times after induction of the neuropathy. The findings are that a loss of all axon types, with a preferential loss of large myelinated axons, is associated with the development of heat hyperalgesia. As the axon loss progresses, however, the hyperalgesia lessens. In addition, at 28 days post surgery there are essentially no large myelinated axons in the distal segment, but the signs of hyperalgesia have almost resolved. These findings indicate that the onset of the hyperalgesia is accompanied by a preferential loss of large fibers and by a lesser but still substantial loss of small myelinated and unmyelinated axons. The subsequent course of the hyperalgesia, however, is not in any obvious way related to the proportions of large myelinated fibers in the affected nerve.