Alterations in primary afferent input to substantia gelatinosa of adult rat spinal cord after neonatal capsaicin treatment.

Primary afferent fibers are divided into three main subgroups: Abeta-, Adelta-, and C-fibers. Morphological studies have demonstrated that neonatal capsaicin treatment (NCT) depletes C-fiber inputs in the spinal dorsal horn; the electrophysiological features of the NCT-induced changes, however, remain unclear. This issue was addressed by performing whole-cell voltage-clamp recordings from substantia gelatinosa (SG) neurons in dorsal root-attached spinal cord slices. When estimated from excitatory postsynaptic currents (EPSCs) evoked by stimulating primary afferent fibers, 24 (49%) of 49 neurons examined exhibited C-fiber EPSCs that were either monosynaptic (n = 15) or polysynaptic (n = 9) in origin; only two of the neurons had Abeta-fiber responses. In NCT rats, however, SG neurons exhibiting C-fiber-mediated EPSCs decreased to 7% (3 of 41 neurons tested), whereas Abeta-fiber EPSCs were observed in 21 (51%) of the neurons, and 14 (67%) of them exhibited monosynaptic ones. There was no change in the cell proportion having Adelta-fiber innervation after NCT. Our electrophysiological data suggest that NCT diminishes primary afferent C-fiber inputs while enhancing Abeta-fiber direct innervation in the SG in adulthood.

Neonatal capsaicin treatment prevents the normal postnatal withdrawal of A fibres from lamina II without affecting fos responses to innocuous peripheral stimulation.

The development of spinal cord sensory pathways has been investigated in postnatal day (P) 21 rat pups following neonatal capsaicin treatment. Capsaicin-induced destruction of C fibres was confirmed by 62% loss of Isolectin B4 (IB4)-binding and an 86% loss of calcitonin gene-related peptide (CGRP)-immunoreactive small diameter dorsal root ganglion cells. Neonatal capsaicin treatment prevented the normal withdrawal of choleragenoid-horseradish peroxidase (B-HRP)-labelled A fibres from lamina II (substantia gelatinosa) to deeper laminae postnatally. A fibre terminals projected more dorsally, extending into 43% of lamina II compared to vehicle-treated littermates. A small cell loss in, and/or shrinkage of, substantia gelatinosa cannot account for this. These support the concept of a competitive interaction between A and C fibre afferents to establish final terminal fields. However the continued exuberant A fibre termination in capsaicin-treated rats did not lead to continued c-fos induction in the superficial dorsal horn by innocuous stimulation. In normal development, exuberant A fibre terminals coincide with c-fos activation in lamina II by innocuous skin stimulation [23]. Despite the continued presence of exuberant A fibre terminals, c-fos was not induced by innocuous peripheral stimulation in P21 capsaicin-treated rats implying that these superficial terminals do not activate lamina II neurons in the same way as in the neonate.