Loss of Spinothalamic Tract Neurons following Neonatal Treatment of Rats with the Neurotoxin Capsaicin

Abstract

The purpose of the present experiments was to determine whether the organization of spinothalamic tract (STT) cells of adult rats was altered following the loss of most of their small-diameter peripheral afferent fibers, resulting from the neonatal administration of capsaicin. Rat pups were randomly assigned to serve as normal controls, to serve as vehicle controls, or to receive subcutaneous injections of capsaicin (50 mg/kg) on postnatal day (PND) 1, 2, 7, or 15; or an injection on PND 1, 3, and 5. When 60 days old, they were anesthetized and received 0.1-μl thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) in the area of the central lateral nucleus (CL), the posterior group (PO), and the ventrobasal complex (VB), or the area of CL or VB. Following a survival time of 48 hr, the animals were perfused, and neuronal HRP reaction product was visualized with tetramethylbenzidine.

The number and distribution of WGA:HRP-labeled STT neurons varied in treated animals with the time of capsaicin injection. Rats injected with capsaicin on or before PND 7 demonstrated a significant reduction of labeled STT neurons from the superficial laminae of the spinal cord. Additionally, lamina I neurons were unlabeled in animals treated before PND 7 even with large thalamic injections. Differences in the distribution of labeled STT neurons could not be demonstrated for animals injected with capsaicin on PND 7 or PND 15, though there was a decrement in the number of labeled neurons in PND 7 animals. In order to make certain that absence of labeled STT neurons was not due to some technical error or to insufficient spread of WGA:HRP at the site of injection, six injections of WGA:HRP were placed in the thalamus of PND 1 and normal adult animals. Where the dense core of reaction product did not extend caudal to the posterior commissure, WGA:HRP-positive neurons were located and distributed similarly to those cases described for large thalamic injections. Neurons in superficial laminae of the nucleus proprius and lamina I of the contralateral spinal cord were labeled where the dense core of the thalamic injection extended into the mesencephalon of PND 1 animals.

These studies indicate that the number and distribution of the cells of origin of the STT are altered in adult rats following their neonatal treatment with the neurotoxin capsaicin, and that this effect is limited to a critical postnatal period.