Number Of Primary Sensory Neurons Research Articles

Corneo‐conjunctival sensory neuron: Types, transduction channels and codification of nerve impulses

The cornea and the conjunctiva are innervated by the peripheral projections of a small number of primary sensory neurons whose somata are located at the ophthalmic region of the trigeminal ganglion. Most trigeminal neurons innervating the ocular surface are small and medium size, and contain neuropeptides such as SP and CGRP. Functionally, ocular surface neurons have been classified into five main neuronal types, based on their response to multiple modalities of stimuli (mechanical forces, heat, cold, H+, chemical substances, etc.). Polymodal nociceptors (activated by several modalities of stimulus, mechanical energy, heat, H+, and chemical irritants), mechanonociceptors (activated by mechanical energy), cold thermoreceptors (activated by temperature reductions and hyperosmolarity) are found in the cornea, the sclera and the conjunctiva. Besides, low‐threshold mechanoreceptors (activated by mechanical forces of low intensity) are found in the corneoscleral limbus and the lid border, and pruriceptors (activated by pruritogen substances) have been described in the tarsal conjunctiva, close to the lid margin.The ability to respond to the different modalities of stimulus lies in the types of transducing channels that each type of neuron expresses at its peripheral nerve endings. Sensory transduction involves the conversion of the physical or chemical stimuli acting on the nerve terminal into electrical energy, that is, into a local change of membrane potential that, if it is large enough, will generate action potentials that will travel along the axon to be processed by the CNS. So that, nerve terminals with TRPV1 channels are directly gated by heat, H+, and several chemical irritants such as capsaicin; nerve terminals with Piezo2 channels will be activated by mechanical forces; TRPM8 channels provide nerve terminals sensitivity to cold and osmolarity increases; et cetera.Ocular sensory neurons also express other ion channels that contribute to coding, that is to help the sensory neuron to establish a correspondence between the characteristics of the stimulus (intensity, temporal course, etc.) and specific parameters of the firing it induces. Voltage‐gated Ca2+, Na+ and K+ channels as well as cyclic nucleotide‐gated channels, among others, contribute to define the firing frequency and pattern to encode the traits of the stimulus. Thus, the ion channels present in the nerve terminals of each class of ocular sensory neuron provide the neurons the ability to detect and encode one or several modalities of stimulus, which constitutes the origin of the different sensations evoked on the ocular surface.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

Corneal sensory nerve function: An overview

Somatosensory innervation of the cornea is provided by the peripheral axons of a small number of primary sensory neurons located in the ophthalmic region of the trigeminal ganglion. Corneal sensory nerve fibres are heterogeneous and may express different neurotransmitters and ion channels involved in transduction and coding of the stimuli acting on the tissue. Based on their activation by one or several types of physical and chemical stimuli, corneal nerve fibres are classified as polymodal nociceptors, mechanonociceptors and cold thermoreceptors. Impulse activity originated at corneal sensory nerves reaches second‐order neurons located at the lower brainstem, from where sensory information travels to the contralateral posterior thalamus and, then, to the brain cortex.After processing, the activation of the different classes of corneal neurons results in different sensations that depend on the type of primary sensory neuron initially activated by the stimulus, although pain is the main sensation elicited by corneal stimulation. Sensations originated at the cornea are explored by esthesiometry, allowing to quantify the threshold, intensity and quality of the evoked sensations. Sensitivity of the ocular surface is reduced with age and altered by several pathological processes that affect sensory innervation, either ocular (such as allergic keratoconjunctivitis, infectious keratitis, eye surgery, hereditary corneal dystrophies, dry eye, etc.) or systemic diseases, such as diabetes and peripheral neuropathies.A prominent feature of ocular nociceptors is their sensitization by the inflammatory mediators released after noxious stimulation or tissue injury, while cold thermoreceptor activity is inhibited by inflammatory substances. Both the spontaneous and the stimulus‐evoked activity increases in sensitized nociceptors, which causes sustained pain and hyperalgesia. After corneal sensory nerves damage (produced as a consequence of an ocular or systemic disease, or by accidental or surgical injury), part of sensory nerves degenerates leading to reduced sensitivity to natural stimulation in the affected area. At the same time, axons start to regenerate and to recover the ability to transduce and encode the stimulus. During this regeneration process, cold thermoreceptor and nociceptor nerves may become hyperexcitable due to changes in their expression/activity of ion channels, which give rise to dryness sensation and ocular neuropathic pain.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

Generation of new neurons in dorsal root Ganglia in adult rats after peripheral nerve crush injury.

The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage.

Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells

Aims Xenon provides effective analgesia in several pain states at sub-anaesthetic doses. Our aim was to examine whether xenon may mediate its analgesic effect, in part, through reducing the activity of transient receptor potential vanilloid type 1 (TRPV1), a receptor known to be involved in certain inflammatory pain conditions. Main methods We studied the effect of xenon on capsaicin-evoked cobalt uptake in rat cultured primary sensory neurons and in human TRPV1 (hTRPV1)-expressing human embryonic kidney 293 (HEK293) cells. We also examined xenon's effect on the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the rat spinal dorsal horn evoked by hind-paw injection of capsaicin. Key findings Xenon (75%) reduced the number of primary sensory neurons responding to the TRPV1 agonist, capsaicin (100 nM–1 μM) by ~ 25% to ~ 50%. Xenon reduced the number of heterologously-expressed hTRPV1 activated by 300 nM capsaicin by ~ 50%. Xenon (80%) reduced by ~ 40% the number of phosporylated ERK1/2-expressing neurons in rat spinal dorsal horn resulting from hind-paw capsaicin injection. Significance Xenon substantially reduces the activity of TRPV1 in response to noxious stimulation by the specific TRPV1 agonist, capsaicin, suggesting a possible role for xenon as an adjunct analgesic where hTRPV1 is an active contributor to the excitation of primary afferents which initiates the pain sensation.

Environmental rotenone treatment destroys primary receptor neurons in the pond Snaillymnaea Stagnalis

Event Abstract Back to Event Environmental rotenone treatment destroys primary receptor neurons in the pond Snaillymnaea Stagnalis Agnes Vehovszky1*, H. Szabo1 and L. Hernadi1 1 Balaton Limnological Research Institute, HAS, Hungary Environmental rotenon treatment of Lymnaea stagnalis attenuates the DAergic functions, resulting locomotory impairment and decreased feeding behavior in a concentration dependent manner. However, we do not know if the attenuated central DAergic system is responsible for the decreased behavioral responses or rotenone primarily destroys the sensory neurons in the skin or the buccal areas which may lead to the cessation of behaviors. Morphological strudies were carried out to test the effects of environmental rotenon treatment (0.5 uM) on primary sensory neurons located in the oral-buccal areas to determine whether impairment of the sensory system leads to the decreased feeding behavior of treated animals. Retrograde neurobiotin tracing via cerebral and buccal nerves which innervate head areas and the oral-buccal cavity revealed a huge number of primary sensory neurons labeled in the lips, and the oral cavity. The tracing via buccal nerves revealed a huge number of labeled sensory neurons in the bucal cavity and the ventral part of the oral cavity which is also innervated by a cerebral nerve. Tracing via cerebro-buccal connectives revealed that a low number of sensory neurons are labeled in the lips and the oral cavity. In rotenon treated animals the neurobiotin tracing via cerebral and buccal nerves failed to label primary sensory neurons either in the lips and mouth or the oral-buccal cavity suggesting that rotenon treatment destroyed primary sensory neurons in body surfaces exposed to rotenone. Since the activity of these sensory cells is required to the initiation of feeding CPG therefore their degeneration may be responsible for the cessation of Lymnaea food intake. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - degenerative disorders Citation: Vehovszky A, Szabo H and Hernadi L (2009). Environmental rotenone treatment destroys primary receptor neurons in the pond Snaillymnaea Stagnalis. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.179 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Mar 2009; Published Online: 05 Mar 2009. * Correspondence: Agnes Vehovszky, Balaton Limnological Research Institute, HAS, Tihany, Hungary, agnes@tres.blki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Agnes Vehovszky H. Szabo L. Hernadi Google Agnes Vehovszky H. Szabo L. Hernadi Google Scholar Agnes Vehovszky H. Szabo L. Hernadi PubMed Agnes Vehovszky H. Szabo L. Hernadi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Projection of Sensory Neurons with Microvilli to the Lateral Olfactory Tract Indicates their Participation in Feeding Behaviour in Crucian Carp

In the olfactory system of vertebrates, a large number of primary sensory neurons terminate in glomeruli in the olfactory bulb, where they make synapses with a significantly smaller number of secondary neurons. We applied small amounts of a lipophilic neural tracer (Dil) in the glomerular regions of the lateral olfactory bulb in crucian carp, and investigated the centrifugal migration of this stain through the secondary neurons towards the brain and peripherally to the sensory neurons of the olfactory epithelium. In preparations where only the secondary neurons of the lateral olfactory tract (LOT) were stained, the majority (76%) of sensory neurons had cell bodies in the intermediate layer of the olfactory epithelium. Scanning electron microscopy revealed that most of the sensory neurons with cell bodies in the intermediate layers of the olfactory epithelium feature microvilli. Based on observations that the secondary neurons of the LOT mediate feeding behaviour, we feel that there is strong evidence to indicate that the sensory neurons that exhibit microvilli are responsible for mediating the behavioural patterns related to feeding. These results are discussed in relation to physiological experiments on the properties of the sensory neurons and to studies of the innervation pattern of sensory neurons.

Endogenous neurotrophin-3 supports the survival of a subpopulation of sensory neurons in neonatal rat

Neurotrophin-3 promotes the differentiation and supports the survival of neuroblasts derived from the neural crest in early development. Neurotrophin-3 also plays an important role in the differentiation and survival of a subpopulation of large sensory neurons after their axons arrive at their targets. Proprioception and mechanoception are lost after gene deletion of neurotrophin-3 or its high-affinity receptor, TrkC. However, the function of neurotrophin-3 during late development and in mature animals is not clear. We have used an antiserum, specific for neurotrophin-3, to neutralize endogenous neurotrophin-3 in postnatal rats to determine its role in late sensory neuron development. Administration of the antiserum for a period of two weeks, but not one week, resulted in a 20% reduction in the number of primary sensory neurons in the dorsal root ganglia and a 19% reduction in the number of myelinated axons in the saphenous nerve. The size distribution histogram also indicated that a subpopulation of large neurons was lost by the neurotrophin-3 antiserum treatment. This neuronal loss was accompanied by reduced cell soma sizes and weights of the ganglia. Immunoreactivities for calbindin and calretinin were reduced in the trigeminal and dorsal root ganglia and nerve fibres surrounding whisker hair follicles. The number of Merkel cells in touch domes labelled with quinacrine and the number of parvalbumin-immunoreactive neurons in the dorsal root ganglia were significantly reduced by the antibody treatment. In contrast, the number of muscle spindles in the gastrocnemius muscle is not reduced by the neurotrophin-3 antiserum. Together, these results indicate that a subpopulation of primary sensory neurons in the neonatal rat requires neurotrophin-3 for their survival and expression of calcium binding proteins. In addition, Merkel cells in touch domes also require neurotrophin-3 for their survival. Thus, endogenous neurotrophin-3 in neonatal rats is critical for the survival and function of a subpopulation of primary sensory neurons and Merkel cells.

Vitamin E affects quantitative age changes in lumbar motoneurons and in their peripheral projections

Vitamin E deficiency was previously found to induce plastic changes in the number of primary sensory neurons and in motoneuron peripheral field projections. In this work, quantitative changes in motoneurons of lumbar segments, in nerve fibres constituting ventral roots and in innervating leg motor fibres were studied in normal and vitamin E deficient rats from 1 to 5 months of age. The number of lumbar motoneurons was found to decrease, while there were no changes in the number of ventral root fibres. An increase in the number of innervating leg motor fibres was observed during ageing in control rats; in vitamin E deficient rats the number of fibres in the ventral roots did not change, as occurred in controls, but the decrease in the number of motoneurons was smaller and the number of innervating leg motor fibres increased further in comparison to the controls. The findings are consistent with the idea that vitamin E deficiency causes a decrease in motoneuron death or, alternatively, that it induces some process partially compensating naturally occurring motoneuron death.

Changes in the number of primary sensory neurons in normal and vitamin-E-deficient rats during aging.

In the dorsal root ganglia (DRGs) of vitamin-E-deficient rats, we previously found an increase in the number of neurons during the first 5 months of life (Cecchini et al., 1993, 1994). This neurogenetic event seems to bring forward in time the increase in the number of primary sensory neurons that Devor et al. (1985) found in normal rats aged more than 1 year, but that other authors have not confirmed. The present study had two aims: first, to verify whether neurogenesis spontaneously occurs in DRGs of 14-month-old Sprague-Dawley rats; and, second, to determine whether the neurogenesis enhanced by vitamin E deficiency continues further in the long run, or whether it stops or reverses into neuron loss. A quantitative and morphometric analysis was performed on neurons of L3-L6 DRGs in 14-month-old normal and vitamin-E-deficient rats: the results obtained were compared to those previously obtained in 1-month-old and 5-month-old animals of both dietetic treatment groups, in order to observe the effects of aging on these neuronal populations. The total number of DRG neurons in the control group was higher in older than in younger animals, whereas the value in the vitamin-E-deficient group was lower in older than in younger animals. The present data confirm that neurogenesis occurs in DRGs of normal rats during adult life. Moreover, they show that once the premature neurogenesis in the deficient rats is completed, no further increase in the number of neurons takes place.

Peptide coexistence in axon terminals within the superficial dorsal horn of the rat spinal cord

The somata of primary sensory neurons have been shown to contain up to four (and possibly more) neuroactive peptides. Although each of these peptides has been separately located in axon terminals within the superficial dorsal horn of the spinal cord, it is not clear whether multiple peptide coexistence is also a feature of terminal varicosities. The aim of this study was to determine whether the peptides substance P (SP) and calcitonin gene-related peptide (CGRP), which are colocalized in the somata of a large number of primary sensory neurons, coexist in the central terminals of these neurons in the spinal cord. The protein A-gold technique of antigen localization was used to screen single boutons in laminae I and II of the rats spinal cord for SP- and CGRP-like immunoreactivity at the ultrastructural level. The results show that SP and CGRP are colocalized within a large number of synaptic boutons in the superficial dorsal horn. Furthermore, evidence was obtained to suggest that both SP and CGRP may be found in the same synaptic vesicle within these boutons. These findings indicate that both SP and CGRP may be coreleased from single terminals in the superficial dorsal horn. This is of considerable interest in view of the reported interaction between SP and CGRP in nociceptive behavioral responses in the rat.

Innervation of rat molar teeth: II. A quantitative analysis of primary sensory neurons innervating a mandibular molar tooth.

This study was conducted to determine the source and number of primary sensory neurons (PSNs) innervating a mandibular molar tooth of a population of 15-18-week-old Sprague-Dawley rats. The pulpal tissue was exposed to horseradish peroxidase (HRP) pellets for 24 hours. Subsequently the animals were perfusion fixed and the following PSN structures were examined for the presence of HRP-labelled cells: trigeminal (TGs) and cervical dorsal root ganglia (DRGs) and mesencephalic nucleus (MN). Only the TGs contained labelled cells and they thus were the sole source of PSN pulpal innervation. The number of TG cells was highly variable, 49-407, but most of this variability was attributable to insufficient HRP filling of the pulp chamber or leakage of HRP into periapical tissue. Selection of TGs whose respective experimental teeth demonstrated that HRP filled and was restricted to the pulp chamber revealed a narrower range of TG cells providing pulpal innervation to the first molars, 142-288, with an average of 213. A detailed mapping of these cells indicated a somatotopic distribution within the mandibular territory of the TGs. It was concluded that these findings represent TG's contribution to the pulpal innervation of this specific population of rat first molar teeth. This suggests that from animal to animal the density of innervation may be quite variable and it is hypothesized that the sensitivity of the pulp would likewise vary. In addition, these findings may contribute to the explanation of why there is variability in the stimulus strength needed to elicit a pain response in the human dentition.

Peripheral Neve Regeneration in Vivo with Tubular Prostheses

AbstractWe have developed a quantitative model which allows assessment of the number of primary motor and sensory neurons which regenerate an axon through a tubular prosthesis bridging a 4–5 mm gap of peripheral nerve (1). Labeled somas of motor and sensory neurons are quantified following retrograde transport of horseradish peroxidase (HRP) applied to the distal stump beyond the bridged transection site. The number of myelinated axons at mid-guide level is also quantified. We have studied biodegradable and nin-biodegradable materials as well as the effects on nerve regeneration of basement membrane materials, and specific proteins added to the nerve guide., Adding a laminin-oontaining gel (Matrigel, Collaborative Research, MA) to the lumen of polyethylene tubes increases the rate of nerve regeneration as well as the maximum distance that can be successfully bridged. Similar effects are seen with collagen-based nerve guides when the laminin-cxitaining gel is incorporated into the tube wall. Addition of highly purified acidic fibroblast growth factor (aFGF) to the lumen of polyethylene tubes filled with collagen significantly increases the number of myelinated axons at mid-tube level and the number of primary sensory neurons labeled with HRP.We coxpared collagen-based nerve guides of different wall porosities. Tubes freely permeable to bovine serum albumin (BSA) contain significantly more myelinated axons (4 week survival) than identical collagen tubes permeable to glucose-size molecules. These and additional experiments demonstrate that manipulation of the extracellular microenvironment of regenerating PNS axons can significantly enhance the early regenerative response.

Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat

Immunohistochemical and radioimmunoassay studies revealed that both CGRP- and SP-like immunoreactivity in the caudal spinal trigeminal nucleus and tract, the substantia gelatinosa and the dorsal cervical spinal cord as well as in cell bodies of the trigeminal ganglion and the spinal dorsal root ganglion is markedly depleted by capsaicin which is known to cause degeneration of a certain number of primary sensory neurons. Higher brain areas and the ventral spinal cord were not affected by capsaicin treatment. Furthermore CGRP and substance P-like immunoreactivity were shown to be colocalized in the above areas and to coexist in cell bodies of the trigeminal ganglion and the spinal dorsal root ganglia. It is suggested that CGRP, like substance P, may have a neuromodulatory role on nociception and peripheral cardiovascular reflexes.