Several plant lectins were used to characterize the cell-surface carbohydrates expressed on sensory ganglion cells and their central terminals in the spinal cord dorsal horn. In the rat, galactose-terminal glycoconjugates on a large subpopulation of small neurons whose central axons project to the substantia gelatinosa were demonstrated with the alpha-D-galactose-specific Griffonia Simplicifolia I-B4 (GSA) lectin. This neuron subset was labelled by alternative D-galactose-, N-Acetylgalactosamine-, and beta Gal(1,3)NAcGal-binding lectins. Similar GSA lectin reactivity was also illustrated in selected peripheral autonomic, gustatory and visceral sensory and enteric neurons, and the accessory olfactory bulb. The sensory neuron-specific isoenzyme, fluoride-resistant acid phosphatase (FRAP) co-localized with the GSA lectin, as did the monoclonal antibody (MAb) 2C5, which is directed against a lactoseries carbohydrate constituting a backbone structure of ABH human blood group antigens. In contrast, calcitonin gene-related peptide-immunoreactivity (CGRP-IR), used as a representative marker of peptidergic neurons, exhibited limited co-localization with GSA. A polyclonal anti-rat red blood cell (RBC) antibody co-localized with GSA, suggesting that lectin-reactive carbohydrates on rat sensory neurons are related to rat RBC antigens. In the human spinal cord, the L-fucose-binding Ulex europaeus-I (UEA) lectin also labelled the substantia gelatinosa; in rabbit, a small sensory ganglion cell subset and the spinal cord substantial gelatinosa was co-labelled by both the GSA and UEA lectins. These studies illustrate significant lectin-reactive cell surface carbohydrate expression by non-peptidergic, FRAP(+) sensory ganglion cells in the rat, and provide a means for visualizing the extensive, non-peptidergic, small sensory ganglion cell subpopulations, probably including a substantial proportion of nociceptive and unmyelinated peripheral axons.

Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or sural nerve with the aim of inducing a standardized nerve injury, as assessed by morphometric analyses of fiber-size spectrum alterations, associated with behavioral manifestations of neuropathic pain. The temporal sequence of axonal degeneration and regeneration was examined in parallel with behavioral analyses of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of 0.028-0.030" inner diameter loosely enclosed sciatic nerves of young rats and elicited relatively uniform axonal degeneration and 'pain'. Large myelinated axons underwent an early and sustained numerical depletion. Both the thinly myelinated and unmyelinated axon populations were initially diminished, but later rose to levels significantly greater than control values, likely the result of: (1) demyelination, (2) early stages of remyelination, (3) regenerative sprouting, and/or (4) collateral sprouting of undamaged unmyelinated axons. Pathological alterations of the injured nerve included edematous swelling, hypertrophy of the perineurial sheath, infiltration of fibroblasts and collagen into the intraneurial compartment, increasing interaxonal space and decreasing order and density of axonal packing. Animals displayed maximal pain-related behaviors, including gait and postural asymmetries and hypersensitivity to mechanical compression and cold, during the 2nd week PO and had largely recovered by approximately 4 weeks PO. Consistent behavioral manifestations of pain were achieved over a wide range of fiber spectrum alteration; however, with the largest cuffs or 'bracelets' used in this study, a substantial axonal fiber spectrum change was produced without inducing pain-related behavior, suggesting that decrement in the number of myelinated axons was not always sufficient to elicit pain. Similar morphometric and pathological results were achieved with sural neuropathy after 0.010" ID cuffs and 14 days PO survival. Considering the lack of correlation between axonal alterations and pain, modification in the local intraneurial microenvironment at the site of injury may be a key component of peripheral pain mechanisms; these include changes in the biochemical milieu, increased intraneurial pressure, and altered nociceptor sensitivity or impulse propagation in the relatively intact unmyelinated axon population.

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Several lines of evidence indicate that tachykinin neuropeptides [substance P (SP), substance K (SK), and neuromedin K (NK)] play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. Surgical specimens of colon were obtained from patients with ulcerative colitis (n = 4) and Crohn disease (n = 4). Normal tissue was obtained from uninvolved areas of extensive resections for carcinoma (n = 6). In all cases, specimens were obtained <5 min after removal to minimize influences associated with degradation artifacts and were processed for quantitative receptor autoradiography by using '2I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle. In contrast, specific NK binding sites were not observed in any area of the human colon. In colon tissue obtained from ulcerative colitis and Crohn disease patients, however, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscularis mucosa, external circular muscle, external longitudinal muscle, and serosa. In addition, very high concentrations of SP receptor binding sites are expressed within the germinal center of lymph nodules, whereas the concentrations of SP and SK binding sites expressed by the external muscle layers are not altered significantly. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations (1000 -2000 times normal) by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.identified within a subpopulation of these sensory neurons (1). The most extensively characterized of these sensory neuropeptides is substance P (SP), a member of the mammalian tachykinin family (Fig. 1), which also includes SK and NK. Though it is clear that SP and SK are expressed by sensory neurons (2) this remains uncertain for NK and derives from difficulty in generating highly specific antibodies for each of the tachykinins since they all share the highly antigenic carboxyl terminus -Phe-Xaa-Gly-Leu-Met-NH2,

A stratified organization of visual, somatic and acoustic representations was observed in the cat SC. Cells of the superficial laminae were exclusively visual. Visual, somatic, and acoustic cells were observed in the intermediate laminae while the deeper laminae were predominantly nonvisual. A detailed examination of the tactile representation revealed a somatotopic plan which was in register with the overlying visuotopy. The magnified representation of central visual fields overlapped the magnified tactile representation of the face and, as visual RFS moved temporally, the underlying tactile RFS were displaced caudal and distal. This topographical overlap can be recognized if the visual field is depicted as a flexible sheet which is stretched over the body with the area centralis superimposed on the nose and the limbs radiating out at an acute angle. The overlapping topographies and similarities in stimulus specificity of somatic and visual cells, as well as the similar behavioral deficits previously described following SC lesions, suggests a functional parallel between modalities in the SC. The possibility that visual, somatic, and acoustic cells converge on a common delivery or distribution system, which is located in the intermediate-deeper SC strata and organizes orienting and following responses on the basis of multimodality cues, is discussed.