The Journal of comparative neurology
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Projection neurons in lamina I, together with those in laminae III-IV that express the neurokinin 1 receptor (NK1r), form a major route through which nociceptive information reaches the brain. Axons of these cells innervate various targets, including thalamus, periaqueductal gray matter (PAG), and lateral parabrachial area (LPb), and many cells project to more than one target. The aims of this study were to quantify projections from cervical enlargement to PAG and LPb, to determine the proportion of spinothalamic neurons at lumbar and cervical levels that were labelled from PAG and LPb, and to investigate morphological differences between projection populations. ⋯ Most lamina III/IV NK1r cells at both levels projected to LPb, but few were labelled from PAG. The great majority of these cells in C7 and over one-fourth of those in L4 were spinothalamic, and at each level some projected to both thalamus and LPb. These results confirm that neurons in these laminae have extensive collateral projections and suggest that different neuronal subpopulations in lamina I have characteristic patterns of supraspinal projection.
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The functional restorative capacity of fetal dopaminergic (DA) transplants is governed by a number of critical parameters including graft location, survival of DA neurons, and transplantation technique. In addition, there is an ongoing controversy whether "too much" or "too little" survival of DA neurons is responsible for the incomplete functional recovery observed in some transplanted Parkinson's disease (PD) patients. Here we investigated two implantation sites, the nucleus accumbens (NAc) and the caudate-putamen unit (CPU), and two different graft distributions within the CPU, i.e., two 0.75 microL deposits (CPU-2) versus six 0.25 microL deposits (CPU-6) in a rat model of PD. ⋯ Furthermore, a correlation analysis revealed a number of inverse relationships between the rate of DA neuron survival and sensorimotor performances, e.g., for skilled forelimb use. DA grafts placed into the NAc induced a partial recovery in drug-induced rotation tests but failed to restore any of the other sensorimotor behaviors tested. Taken together, these data have important implications both for a better understanding of the complex functional graft-host interactions as well as for the further optimization of clinical neural transplantation strategies in neurodegenerative diseases.
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The skin is innervated by two populations of unmyelinated sensory fibers, the peptidergic and nonpeptidergic, which transmit nociceptive information to the central nervous system. The peptidergic population expresses neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) and has both cutaneous and visceral targets. The nonpeptidergic population expresses the purinergic receptor P2X(3), binds the isolectin B4 (IB4), and innervates mainly the epidermis. ⋯ The distribution of P2X(3)-IR fibers in the epidermis was far more extensive than the distribution of CGRP-IR fibers. P2X(3)-IR fibers also innervate hair follicles but were rarely found in close proximity to glands and blood vessels. The present results suggest a primary role for P2X(3)-IR fibers in the detection of noxious stimuli in cutaneous tissue and provide an anatomical basis for future studies examining a possible functionally distinct role of nonpeptidergic nociceptors in the transmission of nociceptive signals.
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Hypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post-injury for 4 hours, 33 degrees C) with gradual rewarming (1 degrees C per hour) for the preservation of tissue and the prevention of injury-induced functional loss. ⋯ Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1-3) and improved forelimb strength, as measured by both weight-supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI.
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Spinal lamina I (LI) neurons play a major role in the transmission and integration of pain-related information that is relayed to higher centers. Alterations in the excitability of these neurons influence chronic pain development, and expression of the neurokinin 1 receptor (NK-1r) is thought to play a major role in such changes. Novel expression of NK-1r may underlie hyperexcitability in new populations of LI neurons. ⋯ Our results revealed that, ipsilaterally, pyramidal neurons were seldom immunoreactive for NK-1r both in saline-injected and in CFA-injected rats, up to 10 days post-CFA. However, a considerable number of pyramidal cells were immunoreactive for NK-1r at 15, 21, and 30 days post-CFA. Our data raise the possibility -- which needs to be confirmed by electrophysiology -- that most LI projection neurons of the pyramidal type are likely nonnociceptive in naive animals but might become nociceptive following the development of arthritis.