The European journal of neuroscience
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The dorsal horn of the spinal cord, which forms the locus of first synapses in pain pathways, is an important site of interaction between calcitonin gene-related peptide (CGRP), substance P and enkephalin--the neuropeptides considered to be especially involved in the regulation of pain perception. Since adjuvant-induced arthritic rats provide a suitable model for peripheral inflammation and hyperalgesia, the possible alterations of immunoreactive CGRP, substance P and enkephalin as well as the binding sites for [125I]hCGRP alpha, [125I]substance P/neurokinin-1, (NK1) and [125I]FK-33-824/mu-opioid receptors were studied in the dorsal horn of the spinal cord receiving projections from the inflamed limbs. In arthritic rats compared to control animals, a bilateral increase in CGRP- and substance P-immunoreactive fibres and the presence of enkephalin-immunoreactive cell bodies were noted in the dorsal horn of the spinal cord. ⋯ Following unilateral section of the peripheral nerve prior to induction of arthritis, CGRP- and substance P-immunoreactive fibres were markedly depleted and no enkephalin-positive neurons were observed in the ipsilateral dorsal horn. Analysis of receptor binding sites in denervated arthritic rats, however, exhibited differential responses, i.e. a significant increase in [125I]hCGRP alpha, a marked decrease in [125I]FK-33-824/mu-opioid and apparently no alteration in [125I]substance P/NK1 receptor binding sites were observed in the ipsilateral dorsal horn compared to the intact contralateral side. These results taken together provide anatomical evidence for a concerted role of these peptides in the regulation of adjuvant-induced hyperalgesia accompanying peripheral inflammation.
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Comparative Study
Differential foci and synaptic organization of the principal and spinal trigeminal projections to the thalamus in the rat.
The thalamus is known to receive single-whisker 'lemniscal' inputs from the trigeminal nucleus principalis (PrV) and multiwhisker 'paralemniscal' inputs from the spinal trigeminal nucleus (SpV), yet the responses of cells in the thalamic ventroposteromedial nucleus (VPM) are most similar to and contingent upon inputs from PrV. This may reflect a differential termination pattern, density and/or synaptic organization of PrV and SpV projections. This hypothesis was tested in adult rats using anterograde double-labelling with fluorescent dextrans, horseradish peroxidase (HRP) and choleragenoid, referenced against parvalbumin and calbindin immunoreactivity. ⋯ PrV endings were also more likely to contact VPM somata (11.0 +/- 4.2% of all labelled terminals) than those from SpV (3.0 +/- 1.0%, P < 0.01). Insofar as primary dendrites are thicker than distal dendrites in VPM, these data suggest a differential distribution of PrV and SpV inputs onto VPM cells that may account for their relative efficacies in dictating the responses of VPM cells to whisker stimulation. Multiwhisker receptive fields in VPM may also reflect direct transmission of convergent inputs from PrV.
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Using in situ hybridization, the expression of the mRNA for a neuropeptide Y (NPY) receptor, was studied in lumbar (L) 4 and 5 dorsal root ganglia (DRGs) of normal rats and at various intervals after unilateral sciatic nerve transection. Twenty percent of all normal DRG neurons were NPY receptor mRNA-positive, and the majority of these neurons were of the small type, with only a few labelled medium-sized and large neurons. In L5 normal ganglia NPY receptor mRNA colocalized with substance P, calcitonin gene-related peptide and galanin mRNAs in small neurons, but not in medium-sized or large neurons containing these peptides. ⋯ No NPY receptor mRNA-positive cells were found in the normal rat gracile nucleus, or in this nucleus after axotomy. These results show that a NPY receptor may be a prejunctional receptor in primary afferent neurons and play a role in the modulation of somatosensory information, both in normal and lesioned primary afferent DRG cells. However, axotomy induced a distinct shift in NPY receptor mRNA expression from small to large neurons, indicating that sensitivity to NPY is switched from one modality to another.(ABSTRACT TRUNCATED AT 400 WORDS)
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Previous studies have shown that following neonatal peripheral nerve injury, adjacent intact myelinated and unmyelinated primary afferents sprout into the central denervated terminal area. The present study investigates this in more detail and goes further, to study the fate of the central terminals of the surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B-HRP), to label the A fibres, or wheatgerm agglutinin (WGA-HRP), to label C fibres were employed to investigate the central consequences of sciatic nerve section and ligation on the day of birth, in adult rats. ⋯ This area was also invaded by intact saphenous A fibres in the L4-5 segments. These results demonstrate that following neonatal nerve section: (i) axotomized primary afferents are able to retain a 'normal' somatotopic map in the rostrocaudal plane; (ii) both A and C fibres from adjacent intact nerves sprout into the denervated territory, but A fibres sprout further caudally; (iii) axotomized A fibres and invading intact A fibres both sprout dorsally into denervated SG. As a result, there is considerable overlap between nerve territories in denervated spinal cord, suggesting that competition for laminar termination sites exists between A and C fibres and also between axotomized and intact primary afferents.
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Excitatory amino acid transmitters are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using N-methyl-D-aspartate (NMDA) receptors, although more recent evidence indicates potential roles for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as well. ⋯ These effects of NBQX were dramatically increased by pretreatment with low doses of NMDA antagonists, whereas adverse effects of NBQX were not potentiated. These data suggest that both non-NMDA and NMDA receptors are critically involved in the kindled state, and that combinations of AMPA and NMDA receptor antagonists provide a new strategy for treatment of epileptic seizures.