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The aim of this study was to examine the expression profile of the vesicular acetylcholine transporter (VAChT), which is a cholinergic pre-synaptic marker, in the lower neural tract following spinal cord injury (SCI) and its effect on coordination of micturition. In adult female Sprague-Dawley rats, SCI was induced by complete transection of the spinal cord at T9. At various time points, 3, 7, 14 and 28 days, after SCI, cystometry was performed on conscious rats. Bladder areflexia was observed during the first week. Twenty-eight days after SCI the rats showed reflex contractions and voiding. The expression of VAChT was examined with immunohistochemistry. The number of VAChT-positive nerve terminals, which were surrounding neuronal soma, was transiently decreased in pelvic ganglion and spinal cord (L1, L2, L6 and S1). In particular VAChT terminals surrounding motor neurons in the ventral horn and autonomic pre-ganglion cells were dramatically decreased from 3 to 14 days after SCI. Similarly, and the number of VAChT-positive fibers in the bladder wall was also decreased. The intensity of VAChT terminals recovered in all above regions in conjunction with recovery of bladder function. These observations indicate that the transient decrease of the VAChT-positive nerve might cause a failure of cholinergic neuronal transmission along the urinary bladder tract after SCI. As the cholinergic system was recovered at least in rat, the functional recovery of neurogenic bladder syndrome in SCI patients may become possible by further understanding the mechanism underlying the recovery of cholinergic system in rat.

The physiological properties of joint capsule mechanical nociceptors of monoarthritic chickens (Gallus domesticus) were studied by recording the electrical activity from single C (Group IV) and A-delta (Group III) fibres dissected from the parafibular nerve. By injecting live Mycoplasma gallisepticum cultures into the ankle joint a typical mycoplasma arthritis was induced which was restricted to a single joint. During the early stage of the disease (7-21 days after infection) there was histopathological evidence of an acute synovitis and the fibres showed evidence of sensitisation. Sensitisation was observed in the significantly increased receptive field size, decreased response thresholds, increased response to joint movement both noxious and innocuous, but only in the C-fibres was there an increase in spontaneous activity. During the more chronic stage of the disease (49-56 days after infection) there was pathological evidence of prolonged synovitis but the sensory fibres responded normally to mechanical stimulation and joint movement. These changes in sensitivity of the joint capsule mechanical nociceptors provides peripheral neural evidence of possible pain experienced during the acute stage of the disease but not at the chronic stage when the disease might be in period of remission. The absence of any clear correlation between pathology and receptor activity demonstrates the difficulty of trying to predict nociceptive consequences in animals on the basis of histopathology.

In order to investigate whether cholera toxin B subunit (CTb) is transported by unmyelinated primary afferents following nerve injury, we transected the sciatic nerves of six rats, and injected the transected nerves (and in three cases also the intact contralateral nerves) with CTb, 2 weeks later. The relationship between CTb and two neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was then examined in neurons in the ipsilateral L4 and L5 dorsal root ganglia, using immunofluorescence staining and confocal microscopy. We also immunostained sections of spinal cord and caudal medulla for CTb, NPY and VIP. Following nerve section, VIP immunoreactivity was increased in laminae I-II of the spinal cord while NPY immunoreactivity was increased in laminae III-IV of the spinal cord and in the gracile nucleus. On the contralateral side, CTb labelling was detected in laminae I and III-V of the dorsal horn of the L4 and L5 spinal segments, as well as in the gracile nucleus. CTb labelling was seen in the same areas on the lesioned side, but with a dramatic increase in lamina II. No VIP or NPY immunoreactivity was observed in L4 and L5 dorsal root ganglia on the side of the intact nerve, but on the lesioned side VIP was detected in many small neurons and NPY in numerous large neurons. In agreement with the report by Tong et al. [J. Comp. Neurol. 404 (1999) 143], we found that while CTb labelling in the dorsal root ganglion on the side of the intact nerve was mainly in large neurons, on the lesioned side CTb was present in dorsal root ganglion neurons of all sizes. The main finding of the present study was that almost all of the VIP- (96%) and NPY- (98%) positive neurons in the dorsal root ganglia on the lesioned side were also CTb-labelled. After nerve injury VIP is upregulated in fine afferents that terminate in laminae I and II, and most of these probably have unmyelinated axons. Since the cell bodies of these neurons were labelled with CTb that had been injected into the transected sciatic nerve, this suggests that many of these fine afferents, which do not normally transport CTb, are capable of doing so after injury.

Injury-induced reorganization of central somatotopic maps is a phenomenon that has proven to be useful for elucidating the mechanisms and time course of neural plasticity. To date, the overwhelming majority of this line of research has focused on such plastic events in cortical areas, at the expense of subcortical structures. In this study, we used multi-unit electrophysiological recording techniques to assess the somatotopic organization of brainstem and thalamic areas following chronic survival from paired median and ulnar nerve section in adult squirrel monkeys. We report that the extent of cutaneously-driven reorganization in both the cuneate nucleus of the brainstem and the ventroposterior lateral nucleus of the thalamus is comparable to that previously documented for area 3b of cortex. These observations are consistent with those previously reported in thalamus, and are unique for brainstem.

We have examined the labeling pattern in the spinal dorsal horn by an intra-sciatic nerve injection of cholera toxin B subunit conjugated horseradish peroxidase (HRP) after transection of the posterior cutaneous nerve and inferior gluteal nerve, and found that the cholera toxin B subunit conjugated HRP labeling in lamina I was expanding into lamina II and there was a shrinking gap between lamina I and lamina III. This result suggests that A-fibre sprouting arise after peripheral nerve injury, but mainly from small calibre Adelta-fibres which terminate in lamina I.

In this study we have tested in the rat, whether trigeminal tractotomy, which deprives the spinal trigeminal nucleus caudalis (Sp5C) of its trigeminal inputs, affected differentially nociceptive responses mediated by C- vs. Adelta-nociceptors from oral and perioral regions. Tractotomy had no effect on the threshold of the jaw opening reflex, induced by incisive pulp stimulation (Adelta-fiber-mediated), but blocked the formalin response (mainly C-fiber-mediated). These results suggest that nociceptive responses mediated by trigeminal C-fibers completely depend on the integrity of the Sp5C, while intraoral sensations triggered Adelta-fibers (especially of dental origin) are primarily processed in the rostral part of the spinal trigeminal nucleus.

Autoradiographic techniques using [3H]citalopram were employed in 8-day-old (P-8) and adult rats to delineate the distribution of high-affinity serotonin (5-HT) uptake sites in the cerebral cortex. In the postnatal rats, [3H]citalopram binding sites were densely distributed in the lower portion of layer III, lamina IV, and upper layer V in the primary visual, somatosensory, and auditory cortices. In the primary somatosensory cortex, these binding sites were arrayed in a manner exactly matching the representation of the body surface as demonstrated by other methods such as staining for cytochrome oxidase (CO) or acetylcholinesterase (AChE). In adult rats, there was no differential distribution of [3H]citalopram binding sites in the cerebral cortex. Neonatal administration of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), resulted in a nearly complete destruction of the 5-HT innervation of the cortex on P-8, but the patterned distribution of [3H]citalopram binding sites remained visible. In contrast, thalamic lesions carried out on P-4 caused a complete loss of the patterned distribution of [3H]citalopram binding sites in rats killed on either P-5 or P-8. These results are consistent with the conclusion that thalamocortical afferents in postnatal rats transiently express high-affinity uptake sites for 5-HT and thus may accumulate this amine.

Male Long-Evans rats received micro-injections of either N-methyl-D-aspartate (NMDA) in the medial septum/vertical diagonal band (MS/DB), 5,7-dihyroxytryptamine (5,7-DHT) in the fimbria/fornix and cingulate bundle or combined NMDA/5,7-DHT micro-injections. NMDA administration caused considerable damage to the MS and enlarged the lateral ventricles. It reduced the activity of choline acetyltransferase as well as the intensity of acetylcholinesterase staining in the hippocampus. 5,7-DHT selectively reduced the concentration of hippocampal serotonin. The rats were assessed for spatial memory in the Morris water maze and the radial arm maze (reference and working memory version). The 5,7-DHT-induced lesion of hippocampal serotonin had no effect by itself on either task. However, it augmented the reference memory impairment caused by the NMDA-induced lesion and delayed the recovery from NMDA-induced impairment of working memory on the radial maze. Combined damage of hippocampal cholinergic and serotonergic afferents did not severely affect spatial memory.

The sequential distribution of transneuronally infected neurons was studied in the olfactory pathway of mice after unilateral inoculation of the challenge virus standard (CVS) strain in the nasal cavity. A first cycle of viral multiplication was observed in a subpopulation of receptor cells scattered in the main olfactory epithelium and in the septal organ. No viral spread from cell body to cell body was reported even in later stages of infection. The second round of viral replication which took place in the ipsilateral main olfactory bulb at 2 and 2.5 days post-inoculation (p.i.), involved second order neurons and periglomerular cells, known to be directly connected with the axon terminals of receptor cells. Also reported as a result of a second cycle of viral replication, was surprisingly the spread of CVS at 2 and 2.5 days p.i. in bulbar interneurons located in the internal plexiform layer and in the superficial granule cell layer, as well as that of 2 ipsilateral cerebral nuclei, the anterior olfactory nucleus and the horizontal limb of the diagonal band. From day 3, a rapid spread of CVS was suggested by detection of virus in all ipsilateral direct terminal regions of the second order neurons and in most tertiary olfactory projections. The locus coeruleus, a noradrenergic nucleus which sends direct afferents to the olfactory bulb, never appeared immunoreactive. In spite of a certain inability of CVS to infect some neuron types, the virus appears relevant to provide new information regarding the complex network of olfactory-related neurons into the CNS.

This paper reviews light- and electron microscopic, histochemical and physiological evidence which demonstrate that peripheral nerve injury in mammals is followed by profound structural and functional changes in the central terminals of the affected primary sensory neurons. Available evidence indicates that at least some of these so-called transganglionic changes are the result of ganglion cell degeneration and death, although other mechanisms are probably in effect as well. Existing data suggest that this ganglion cell death does not effect all types of ganglion cells equally, but do not permit a clearcut answer to the question of which kinds of ganglion cells are affected more than others. Results from studies with microtubule inhibitors and antibodies to nerve growth factor are compatible with the notion that depletion of retrogradely transported trophic factors is involved in the production of certain transganglionic changes. This issue needs further examination, however. Physiological studies indicate marked alterations in certain primary afferent synaptic connections after peripheral nerve lesions. So far, these changes have not been satisfactorily correlated with the structural changes induced by similar lesions. Further studies on the structural and functional response of primary sensory neurons to peripheral nerve injury are likely to contribute to the understanding of the frequent failure to regain normal sensory functions after peripheral nerve lesions in man, as well as of the basic aspects of lesion-induced changes in general in the peripheral and central nervous system.