Needlestick Distal Nerve Injury in Rats Models Symptoms of Complex Regional Pain Syndrome

Abstract

Complex Regional Pain Syndrome (CRPS)-I consists of chronic limb pain and dysautonomia triggered by traumas that sometime seem too trivial to be causative. Several pathological studies have identified minor distal nerve injuries (DNIs) in CRPS-I patients, but retrospective studies cannot establish causality. Therefore, we, prospectively investigated whether DNIs are sufficient to cause CRPS-like abnormalities in animals. We used needlestick, a cause of human CRPS, to evaluate lesion-size effects. Left tibial nerves of male Sprague-Dawley rats were transfixed once by 30G, 22G, or 18G needles. Unoperated and sham-operated rats provided controls. Hindpaw sensory function, edema, and posture were measured. At Day-7 postoperatively, thresholds for ipsilateral-hindpaw withdrawal from Semmes-Weinstein monofilaments were reduced by > or =51% in 0% of sham-operated controls; 67% of rats that received 18G-DNI, 88% that received 22G-DNI, and 89% that received 30G-DNI. Fifty-seven percent of all DNI rats had contralateral hindpaw "mirror" changes. The prevalence and severity of allodynia appeared independent of lesion size. Hyperalgesic responses to cold and pinprick applied to the plantar hindpaw were less common and were ipsilesional only, as was neurogenic hindpaw edema. Ipsilesional-only, tonic, dystonic-like hindpaw postures were evident in 42% of 18G-DNI, 6% of 22G-DNI, and no 30G-DNI or sham-operated control rats. The prevalence of postural abnormalities correlated with needle diameter (P = 0.001). Counting protein gene product 9.5-immunolabeled axons in skin biopsies from rats' ipsilesional hindpaws demonstrated mean reductions of 0% after 30G-needlestick, 15% after 22G-needlestick, and 26% after 18G-needlestick, which closely reproduces the 29% mean epidermal neurite losses of CRPS-I patients. Needlestick DNI models several clinical and pathological features of human CRPS and provides direct prospective evidence that even minor DNI can cause CRPS-like abnormalities in rats.