Pain behavior and nerve electrophysiology in the CCI model of neuropathic pain

Abstract

Experimental painful peripheral neuropathy induced by chronic constriction injury (CCI) of the sciatic nerve results in cutaneous thermal and mechanical allodynia of the hind limb. Our histological studies indicate that the major pathology in the CCI model is a loss of large diameter myelinated fibers distal to the site of injury. Electrophysiological recordings from axons central to the lesion that respond to electrical stimulation distal to it, revealed severe fiber loss, reflected by a decrease (P < 0.05) from 5.2+/-6.8 to 0.5+/-0.1 axons/microfilament 5-9 days post operatively (dpo). At 12-15th dpo some recovery was seen, i.e. 1.5+/-0.28 axons/microfilament in the CCI group. The ratio of A- to C-axons in the control group remained constant throughout the experiment. A distinct area in the paw served by the injured nerve was selected to study the response of axons in each microfilament to mechanical stimulation with von Frey monofilaments. In the control group, 91%+/-0.6 of the microfilaments had at least one axon with a receptive field in this area. This decreased to 17%+/-2.9 in the CCI group 5-9 dpo, but had partially recovered to 44+/-4.2% by 12-15-dpo. Our conclusion is that in the CCI model there is an equal reduction in the number of A and C axons conducting past the lesion site, thus preserving a constant ratio between the two fiber populations. This is true despite the apparent preservation of C-fibers observed in previous histological studies.