Autonomic Neuroscience: Basic and Clinical 84 (2000) 111–117 www.elsevier.com / locate / autneu Short communication NADPH–diaphorase reveals presumptive sympathetic primary afferents in the developing human spinal cord a a,b, * Jennifer A. Foster , Patricia E. Phelps a Department of Physiological Science, UCLA, Box 951527, Los Angeles, CA 90095-1527, USA b Brain Research Institute, UCLA, Los Angeles, CA 90095, USA Received 12 August 1999; received in revised form 25 May 2000; accepted 15 June 2000 Abstract Numerous studies have elucidated two visceral afferent pathways in the spinal cord of mammals, the lateral collateral pathway (LCP) and the medial collateral pathway (MCP). The present study utilized NADPH–diaphorase histochemistry to visualize afferent pathways in the developing human thoracolumbar spinal cord. Diaphorase-positive fiber bundles, strikingly similar to the previously defined LCP and MCP, were observed coursing along the lateral and medial aspects of the dorsal horn to the base of the dorsal horn, the intermediate gray, and / or the dorsal commissure. Furthermore, some axons forming the MCP crossed in the dorsal commissure to the contralateral side of the spinal cord. In addition, axons projecting in the LCP often appeared to terminate within clusters of diaphorase-labeled sympathetic preganglionic neurons, supporting the concept that monosynaptic connections may exist between primary afferents and autonomic motor neurons. Thus, nitric oxide may be involved in both afferent and efferent neurons in reflex pathways of the human sympathetic nervous system.  2000 Elsevier Science B.V. All rights reserved. Keywords: Sympathetic preganglionic neurons; Nitric oxide; Dorsal root ganglion 1. Introduction and de Groat, 1985; Morgan et al., 1986). Both of these centrally-directed afferent projections of the DRG form Sensory (afferent) receptors throughout the body com- two pathways in the spinal cord, the lateral collateral municate with the central nervous system via cells of the pathway (LCP) and the medial collateral pathway (MCP). dorsal root ganglia (DRG). The central processes of these After exiting Lissauer’s tract, axons of the LCP course DRG neurons pass through the dorsal roots into the dorsal along the lateral border of the dorsal horn. From there, spinal cord. Upon entering Lissauer’s Tract, the axons they may then extend into the base of the dorsal horn typically bifurcate, creating ascending and descending (laminae V–VI), the adjacent intermediate gray (laminae branches that further give rise to collaterals. As these VII), and/or the dorsal commissure (lamina X). Axons in primary afferent collaterals enter the dorsal horn, they the MCP also project to the dorsal commissure and the specifically project to various laminae within the spinal base of the dorsal horn, but they travel along the medial cord, characteristic of their given origin and function border of the dorsal horn. Both the LCP and MCP have (Brown, 1981; Willis and Coggeshall, 1991). been found to project across the dorsal commissure to the Numerous studies utilizing the anterograde transport of same target areas in the contralateral side of the spinal horseradish peroxidase (HRP) have identified two distinct cord. visceral afferent pathways: those that course with the NADPH–diaphorase histochemistry of the spinal cord in parasympathetic efferents (Morgan et al., 1981; de Groat et rats, cats, and dogs has revealed a labeled fiber pathway al., 1981; Nadelhaft and Booth, 1984; Bessant and Rober- along the lateral dorsal horn that resembles the LCP tson-Rintoul, 1986) and those that course with sympathetic (Vizzard et al., 1993a; 1994a,b,c, 1997; Marsala et al., axons (Ciriello and Calaresu, 1983; Kuo et al., 1983; Kuo 1998). However, this pathway has only been clearly identified as diaphorase-positive at lower lumbar and sacral spinal cord levels, and not at thoracic levels (Vizzard et al., *Corresponding author. Tel.: 11-310-825-7264; fax: 11-310-206- 1994a,c, 1997). Nonetheless, dorsal rhizotomy experiments 3987. E-mail address: pphelps@physci.ucla.edu (P.E. Phelps). in the rat L6-S1 spinal cord have proven that this 1566-0702 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S1566-0702(00)00189-2