Distinct localization and target specificity of galanin-immunoreactive sympathetic preganglionic neurons of a teleost, the filefish Stephanolepis cirrhifer

Immunoreactivity for galanin was examined in the sympathetic preganglionic neurons in the spinal cord, adrenal glands, sympathetic ganglia, and some sensory ganglia of the filefish Stephanolepis cirrhifer. Galanin-immunoreactive neurons were found only in the rostral part, but not in the caudal part of the central autonomic nucleus (a column of sympathetic preganglionic neurons of teleosts). Many galanin-immunoreactive nerve terminals were found in contact with neurons in the celiac ganglia and the cranial sympathetic ganglia on both sides of the body. Most neurons encircled by galanin-immunoreactive nerve fibers were negative for tyrosine hydroxylase. Galanin-immunoreactive nerve fibers were very sparse in the spinal sympathetic paravertebral ganglia. No galanin-immunoreactive nerve fibers were found in the adrenal glands. No sensory neurons of the trigeminal, vagal, or spinal dorsal root ganglia were positive for galanin-immunoreactivity. These results suggest that galanin-immunoreactive sympathetic preganglionic neurons have distinct segmental localization and might project specifically to a population of non-adrenergic sympathetic postganglionic neurons in the celiac and cranial sympathetic ganglia.     

Pituitary adenylate cyclase activating polypeptide-immunoreactive sensory neurons innervate rat adrenal medulla

Rat adrenal chromaffin cells were invested by a dense network of nerve fibers immunoreactive to pituitary adenylate cyclase activating polypeptide-38 (PACAP-IR). Immunohistochemical studies demonstrated the presence of PACAP-IR in nodose and dorsal root ganglion cells, but not in neurons of the intermediolateral cell column and other autonomic nuclei of the thoracic and upper lumbar spinal cord. Somata of the T7 to T12 paravertebral ganglia were PACAP-negative. A few lightly labeled neurons were occasionally noted in the dorsal motor nucleus of the vagus. Injection of the retrograde tracer Fluorogold into the left adrenal medulla 3 days prior to sacrifice resulted in the labeling of a population of neurons in the ipsilateral spinal cord intermediolateral cell column (T1 to L1), ipsilateral and contralateral nodose ganglia and ipsilateral dorsal root ganglia from T7 to T10 inclusive. A small number of lightly labeled somata was occasionally noted in the dorsal motor nucleus of the vagus. Combined retrograde tracing and PACAP immunohistochemistry showed that a population of Fluorogold-containing nodose and dorsal root ganglion cells were also PACAP-positive. Pre-treatment of the rats with capsaicin caused a marked reduction of the PACAP-IR in the adrenal gland as well as in the superficial layers of the dorsal horn and caudal spinal trigeminal nucleus. These findings, in conjunction with the apparent absence of PACAP-IR in spinal sympathetic preganglionic neurons, sympathetic postganglionic neurons, and dorsal motor nucleus of the vagus, raise the possibility that PACAP-IR fibers observed in the adrenal medulla are primarily sensory in origin. As a corollary, catecholamine secretion from chromaffin cells may be modulated by the peptidergic sensory afferents in addition to the cholinergic sympathetic preganglionic nerve fibers.     

Variation in number of small intensely fluorescent cells (SIF cells) in rat superior cervical ganglia

Changes in the relative synthesis rates of a number of specific proteins from rat dorsal root ganglia (DRG) were observed in response to transection of the sciatic nerve. The pattern of these changes was compared to that in rat sympathetic ganglia after transection of the postganglionic nerves. Although the overall pattern of proteins synthesized, and the pattern of changes seen after nerve transection, were quite similar in both ganglia, some specific differences were observed.     

Transport of endosomal early antigen 1 in the rat sciatic nerve and location in cultured neurons

Early endosomal antigen 1 (EEA1) is known to be a marker of early endosomes and in cultured hippocampal neurons it preferentially localizes to the dendritic but not the axonal compartment. We show in cultured dorsal root ganglia and superior cervical ganglia neurons that EEA1 localizes to the cell bodies and the neurites of both sensory and sympathetic neurons. We then show in vivo using a ligated rat sciatic nerve that EEA1 significantly accumulates on the proximal side and not on the distal side of the ligation. This suggests that EEA1 is transported in the anterograde direction in axons either as part of the homeostatic process or to the nerve ligation site in response to nerve injury.     

Secretoneurin-like immunoreactivity in rat sympathetic, enteric and sensory ganglia

Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals surrounding many of the postganglionic neurons of the superior cervical, stellate, paravertebral chain ganglia, coeliac/superior mesenteric and inferior mesenteric ganglia. Postganglionic neurons of the superior cervical and other sympathetic ganglia exhibited low-to-moderate levels of SN-LI. In all these sympathetic ganglia, clusters of small diameter (<10 μm) cells, which may correspond to the small intensely fluorescent (SIF) cells, were found to be intensely labeled. Surgical sectioning or ligation of the cervical sympathetic trunk for 7–10 days resulted in a nearly total loss of SN-LI fibers in the superior cervical ganglia, whereas immunoreactivity in the postganglionic neurons and small diameter cells remained essentially unchanged. In the thoracolumbar and sacral segments of the spinal cord, SN-LI nerve fibers were detected in the superficial layers of the dorsal horn as well as in the intermediolateral cell column (IL_p). Occasionally, SN-LI somata were noted in the IL_p. SN-LI nerve fibers formed a delicate plexus underneath the capsule of the adrenal gland, some of which traversed the adrenal cortex and reached the adrenal medulla. While heavily invested with SN-LI nerve terminals, chromaffin cells seemed to express a low level of SN-LI. In the enteric plexus, varicose SN-LI nerve fibers and terminals formed a pericellular network around many myenteric and submucous ganglion cells; the ganglionic neurons were lightly to moderately labeled. A population of ganglion cells in the dorsal root, nodose and trigeminal ganglia exhibited moderate-to-strong SN-LI. The detection of SN-LI in nerve fibers and somata of various sympathetic ganglia, enteric plexus and adrenal medulla and in somata of the sensory ganglia implies an extensive involvement of this peptide in sympathetic, enteric and sensory signal processing.     

Retrograde tracing shows that CGRP-immunoreactive nerves of rat trachea and lung originate from vagal and dorsal root ganglia

The origins of sensory innervation of the lower respiratory tract are thought to be principally the nodose and jugular ganglia of the vagus nerve. It has been suggested and partially demonstrated that there is also a component arising from dorsal root ganglia, but the segmental levels involved are not known precisely. We have therefore investigated the origins of sensory nerves within the rat respiratory tract, particularly those containing calcitonin gene-related peptide (CGRP), using the technique of retrograde axonal tracing combined with immunohistochemistry. Injections of True blue were made into extra-thoracic trachea (n = 4 rats) and percutaneously into the right and left lung (n = 4 each). Retrogradely labelled neuronal perikarya were detected in vagal and dorsal root ganglia, and sympathetic chain ganglia. CGRP-immunoreactive cells were seen only in vagal and dorsal root ganglia. Tracheal innervation arose bilaterally in the vagal sensory ganglia but those on the right side represented the principal source; the majority of CGRP-containing neurons occurred in the jugular ganglion. A very small component of labelling occurred in spinal ganglia at levels C2-C6. The sensory innervation of the lungs was seen to arise predominantly from the ipsilateral dorsal root ganglia (45% of cells CGRP-immunoreactive) at levels T1-T6. In contrast to the trachea, the contribution of vagal sensory neurones to the lungs appeared to be less than that of the spinal ganglia. These results show that the sensory innervation of the rat lungs has a major origin in the dorsal root ganglia, in which almost half of the involved neurons contain CGRP, and confirm that most CGRP-immunoreactive nerves in the trachea arise in the right jugular ganglion.     

Time course analysis of sensory axon regeneration in vivo by directly tracing regenerating axons

Most current studies quantify axon regeneration by immunostaining regeneration-associated proteins,representing indirect measurement of axon lengths from both sensory neurons in the dorsal root ganglia and motor neurons in the spinal cord.Our recently developed method of in vivo electroporation of plasmid DNA encoding for enhanced green fluorescent protein into adult sensory neurons in the dorsal root ganglia provides a way to directly and specifically measure regenerating sensory axon lengths in whole-mount nerves.A mouse model of sciatic nerve compression was established by squeezing the sciatic nerve with tweezers.Plasmid DNA carrying enhanced green fluorescent protein was transfected by ipsilateral dorsal root ganglion electroporation 2 or 3 days before injury.Fluorescence distribution of dorsal root or sciatic nerve was observed by confocal microscopy.At 12 and 18 hours,and 1,2,3,4,5,and 6 days of injury,lengths of regenerated axons after sciatic nerve compression were measured using green fluorescence images.Apoptosis-related protein caspase-3 expression in dorsal root ganglia was determined by western blot assay.We found that in vivo electroporation did not affect caspase-3 expression in dorsal root ganglia.Dorsal root ganglia and sciatic nerves were successfully removed and subjected to a rapid tissue clearing technique.Neuronal soma in dorsal root ganglia expressing enhanced green fluorescent protein or fluorescent dye-labeled microRNAs were imaged after tissue clearing.The results facilitate direct time course analysis of peripheral nerve axon regeneration.This study was approved by the Institutional Animal Care and Use Committee of Guilin Medical University,China(approval No.GLMC201503010)on March 7,2014.     

Neuronotrophic activities accumulate in vivo within silicone nerve regeneration chambers

Rat sciatic nerves can be transected and their proximal and distal stumps sutured into the openings of cylindrical silicone chambers. Anatomical regeneration has been demonstrated across 10 mm long chambers containing both stumps, although little or no axonal outgrowth occurs in chambers omitting the distal stump or exceeding the 10 mm length. We have previously shown that chambers containing both proximal and distal stumps accumulate within days of implantation a clear fluid containing neuronotrophic factors (NTFs) directed to neurons from neonatal mouse dorsal root ganglia. We report here that these chamber fluids also have considerable neuronotrophic activity for chick embryo neurons from embryologic day 4 (E4) lumbar spinal cord, E12 sympathetic ganglia, E12 (but not E8) dorsal root ganglia and E8 ciliary ganglia. Thus, the neuronal types supported by trophic factors of these fluids include all those which contribute axons to the sciatic nerve, namely sensory, spinal motor, and sympathetic. In fluid collected 1 week after implantation, NTF levels directed to different neurons varied independently from one another in chambers with different nerve insertions, suggesting that these activities reside in separate factors. Fluid collected from chamber arrangements allowing little proximal fiber regrowth did not always contain correspondingly lower titers of NTFs. However, generally higher titers of all NTFs were found in chambers containing either or both nerve stumps that in nerve-free chambers. Fluids collected from nerve-containing chambers were subjected to heat, dialysis or trypsin treatments. The behavior of their neuronotrophic activities suggests their association with proteins.     

Expression of low-affinity neurotrophin receptor p75NTR in the peripheral nervous system of human neuropathies

Expression of low-affinity neurotrophin receptor (p75^NTR) was immunohistochemically examined in the peripheral nerve trunks, dorsal root ganglia, sympathetic nerve ganglia and spinal cords in various human neurological diseases manifesting peripheral neuropathies. p75^NTR was expressed in the nerves with axonal degeneration, and was also prominent in the nerves with newly regenerating axons. In contrast, axonal pathology tended to reduce the expression of p75^NTR in the neuronal perikarya of the dorsal root genglion and sympathetic nerve ganglion neurons. In the ventral and lateral horn cells, the p75^NTR immunoreactivity was not detected in the normal and diseased nerves except for amyloid polyneuropathy. These p75^NTR expressions in the diseased human peripheral nervous tissues would be regulated by an underlying pathology-related process, and could play a role in peripheral nerve repair. Received: 28 April 1997 / Revised: 5 August 1997 / Revised, accepted: 17 November 1997     

The origin of catecholaminergic nerve fibers in the subdiaphragmatic vagus nerve of rat.

It is known that the vagus nerve contains catecholaminergic fibers. However, the origin of these fibers has not been systematically examined. In this study, we addressed this issue using retrograde tracing from the subdiaphragmatic vagus nerve combined with immunocytochemistry. The cervical and thoracic sympathetic trunk ganglia, the nodose ganglia and the dorsal motor nucleus of the vagus nerve were examined following injection of Fluoro-Gold or cholera toxin horseradish peroxidase conjugate into the trunks of the subdiaphragmatic vagus nerve of rats. Numerous retrogradely labeled neurons were seen in the nodose ganglion and the dorsal motor nucleus of the vagus nerve. Very few labeled neurons were found in the sympathetic ganglia (less than 0.06% of the neurons in either superior cervical ganglion or cervicothoracic ganglion were retrogradely labeled). Double labeling with immunofluoresence for catecholamine synthesizing enzymes revealed that: (1) 92% of all Fluoro-Gold retrogradely labeled tyrosine hydroxylase immunoreactive neurons were found in parasympathetic sources (75% in the dorsal motor nucleus of the vagus nerve and 17% in the nodose ganglia), and only 8% in the cervicothoracic sympathetic ganglia; (2) 12% of the retrogradely labeled catecholaminergic neurons in the dorsal motor nucleus of the vagus nerve were also dopamine-beta-hydroxylase immunopositive neurons; (3) 70% of the retrogradely labeled neurons in the sympathetic ganglia were tyrosine hydroxylase immunopositive and 54% of these catecholaminergic neurons contained dopamine-beta-hydroxylase, while 30% of the retrogradely labeled neurons were non-catecholaminergic neurons. These results indicate that catecholaminergic fibers in the abdominal vagus nerve are primarily dopaminergic and of parasympathetic origin, and that only an extremely small number of these fibers, mostly noradrenergic in nature, arise from postganglionic sympathetic neurons.     

Extensive demyelinating changes in the peripheral nerves of Crow-Fukase syndrome: a pathological study of one autopsied case

Summary Pathological changes of the peripheral nervous system in one autopsied case of Crow-Fukase syndrome (POEMS syndrome) was systemically examined. Distally accentuated myelinated axon loss was observed in the peripheral nerve trunks, ventral and dorsal spinal roots, but was not observed in the fasciculus gracilis. Segmental demyelination and remyelination associated with focal excessive myelin outfolds were the most characteristic features, the distribution of which was more prominent in the proximal nerve trunks and the spinal nerve roots. Endoneurial edema was present, and focal perivascular T lymphocyte accumulation was occasionally observed in the spinal nerve roots and proximal nerve trunks. Neurons in the sympathetic ganglia, dorsal root ganglia and ventral horns were well preserved.Supported by grants from the Ministry of Welfare and Health of Japan     

Inflammatory Changes in Paravertebral Sympathetic Ganglia in Two Rat Pain Models

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.     

Origin of galanin-immunoreactive nerve fibers in the rat paracervical autonomic ganglia and uterine cervix.

Retrograde axonal tracing with fluorogold in conjunction with immunohistochemistry was used to examine the source of galanin-immunoreactive nerve fibers in the paracervical ganglia and uterine cervix of the female rat. Immunohistochemistry revealed galanin-immunoreactive neuron somata in lumbosacral dorsal root ganglia and around the central canal of the lumbosacral spinal cord (lamina X). Injection of fluorogold into the paracervical ganglia resulted in labelled cells in dorsal root ganglia and the sacral parasympathetic nucleus of the spinal cord; but fluorogold-labelled, galanin-immunoreactive cells were found only in dorsal root ganglia. Injection of the tracer in the cervix resulted in labelled cells in the paracervical ganglia and dorsal root ganglia; however, fluorogold-labelled, galanin-immunoreactive cells were again evident only in dorsal root ganglia. It is suggested that the galanin-immunoreactive nerve fibers and varicosities in the paracervical ganglia and uterine cervix are sensory fibers from spinal dorsal root ganglia. The galanin-immunoreactive varicosities in the ganglia could play a role in the modulation of pelvic visceral activity, while those in the musculature of the cervix could influence contractility.     

Innervation of the spleen in the rat: Evidence for absence of afferent innervation

Catecholaminergic fibers in the spleen have been well characterized in the rat and this innervation is believed to be an important source of modulation of the immune system. The presence or role of afferent feedback from the spleen has not been systematically investigated. We have examined whether the spleen receives afferent innervation from sensory ganglia and also have assessed the sources of efferent innervation to the spleen in the rat. The fluorescent retrograde anatomical tracers fluoro-gold (FGo) or fast blue (FB) were injected into the spleens of adult female rats and dorsal root, sympathetic chain, nodose, and celiac-mesenteric plexus ganglia were collected. In additional animals, the spleen was either injected with the anatomical tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or else regular HRP was applied to the cut end of the splenic nerve. Also, we examined the effects of cutting the splenic nerve on the retrograde labeling of cell bodies in the ganglia and on the catecholamine histochemistry of the spleen. The neuroanatomical results were based primarily upon the tracer FGo and verified that the celiac-mesenteric plexus ganglia provide a major efferent input to the spleen. Furthermore, lower thoracic sympathetic chain ganglia provide an additional and substantial efferent supply to the spleen. Cutting of the splenic nerve prevented retrograde labeling of cell bodies in the celiac-mesenteric plexus ganglia and sympathetic chain ganglia of rats injected with tracers into the spleen and also eliminated catecholamine histofluorescence in the spleen. In terms of afferent labeling, the results with FGo indicated that there were no cell bodies labeled in afferent ganglia following splenic injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Origin of sympathetic and sensory innervation of the elbow joint in the rat: A retrograde axonal tracing study with wheat germ agglutinin conjugated horseradish peroxidase

After injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the elbow joint of adult rats, labeled neurons were found in the stellate and the T2-T4 ganglia of the ipsilateral sympathetic trunk, and also in dorsal root ganglia at the C4–T4 levels. Most labeled sympathetic cells, 90% or more, were located in the stellate ganglion. The sensory innervation to the joint originated mainly from the dorsal root ganglia at the levels of C7–T1.     

Peptide-containing neurons projecting to the vocal cords of the rat: retrograde tracing and immunocytochemistry

The distribution and origin of neuropeptide Y-, vasoactive intestinal peptide- and calcitonin gene-related peptide-containing nerve fibers and adrenergic (dopamine-beta-hydroxylase-containing) fibers in the rat larynx were studied by retrograde tracing and selective denervations in combination with immunocytochemistry. An injection of the retrograde tracer True Blue to the right vocal cord resulted in the appearance of labelled nerve cell bodies in the ipsi- and contralateral superior cervical and stellate ganglia, the thyroid ganglia, the jugular-nodose ganglionic complexes, in the ipsilateral trigeminal and dorsal root ganglia at levels C2 and C3 and in local tracheal ganglia. Judging from the number of labelled nerve cell bodies, the jugular-nodose ganglionic complexes, dorsal root ganglia and superior cervical ganglia provide the greater part of the vocal cord innervation. Most of the True Blue-labelled nerve cell bodies in the superior cervical and stellate ganglia contained neuropeptide Y. In the thyroid ganglia the majority of labelled nerve cell bodies contained vasoactive intestinal peptide. In the jugular-nodose ganglionic complex and the dorsal root ganglia the majority of the labelled nerve cell bodies stored calcitonin gene-related peptide. Retrograde tracing and denervation studies revealed that all noradrenaline- and the majority of neuropeptide Y-containing nerve fibers emanate from the superior cervical and stellate ganglia. A minor population of neuropeptide Y-containing nerve fibers originate in local tracheal ganglia. The vasoactive intestinal peptide-containing nerve fibers originate in the thyroid ganglion and local tracheal ganglia, whereas calcitonin gene-related peptide-containing nerve fibres emanate from the dorsal root ganglia (C2-C3), the trigeminal ganglia and the jugular-nodose ganglia.     

The cell bodies of origin of sympathetic and sensory axons in some skin and muscle nerves of the cat hindlimb

Cell bodies of sensory and sympathetic axons projecting to skin and skeletal muscle of the cat hindlimb have been labeled retrogradely with horseradish peroxidase (HRP) in order to study location, size, and numbers of the somata of these neurons. HRP was applied to the freshly transected axons of nerves supplying hairy skin (superficial peroneal, SP; sural, Su), hairy and hairless skin of the paw (medial plantar, MP), or skeletal muscle (gastrocnemius-soleus, GS). Serial sections of lumbosacral dorsal root and sympathetic ganglia were studied after standard histochemical processing. Additionally, the numbers of myelinated fibers in the same nerves were determined. All sensory somata and 99.4% of sympathetic cell bodies were located ipsilaterally. Sensory somata were commonly restricted to two adjacent dorsal root ganglia (usually L6–7 for SP, MP; L7-S1 for Su, GS). Although sympathetic somata were more widely distributed rostrocaudally, their maximum frequency always occurred in the segmental ganglia immediately rostral to the sensory outflows, i.e., corresponding to rami communicantes grisei. Dimensions of sympathetic somata varied little between populations projecting to different tissues and were unimodally distributed. The size distributions of sensory somata were characterized by a peak between 10 and 20 μm radius, similar to sympathetic somata, and a varying smaller number of cells ranging up to 60 μm radius. Each nerve had a characteristic distribution profile of afferent somata. A population of very small cells was only present in GS, while the largest sensory somata in GS and MP were bigger than those in SP and Su. Numerical analysis of the data disclosed the characteristic composition of both myelinated and unmyelinated fibers in each nerve studied.     

The origin of sensory nerve fibers that innervate the submandibular salivary gland in the rat

The origin of sensory nerves that innervate the submandibular salivary gland was investigated in the rat. After application of wheat germ agglutinin-horseradish peroxidase to the cut endings of the sympathetic and parasympathetic nerve branches at the hilus of the gland, labeled cells were mainly found in the dorsal root ganglia and the trigeminal ganglion, respectively. The labeled neurons in these ganglia were of various sizes compared to unlabeled neurons, suggesting that the sensory nerves of the gland conduct various modalities of sensory information.     

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed.Peritoneal lesions (n = 40) and healthy peritoneum (n = 12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density.Peritoneal fluids from patients with endometriosis (n = 40) and without endometriosis (n = 20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH.We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia.In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain.     

p75NGFR immunoreactivity in normal prenatal human dorsal root ganglia

The purpose of the present study was to examine immunohistochemically the expression of the low-affinity p75 nerve growth factor receptor in the dorsal root ganglia from 12 human fetuses (gestational ages, 10-24 weeks) located in three different spinal segments (cervical, thoracic, and lumbosacral), using a monoclonal mouse-antihuman low-affinity p75 nerve growth factor receptor antibody. The low-affinity p75 nerve growth factor receptor immunoreactivity was present within the dorsal root ganglia and the surrounding nerve fibers in all spinal segments at the different gestational ages examined. From 10 weeks of gestation, three different types of neuronal staining were observed: dorsal root ganglia neurons without low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type I neurons), neurons displaying weak low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type II neurons), and neurons manifesting intense low-affinity p75 nerve growth factor receptor immunoreactivity (classified as type III neurons). The distribution of the three types of neurons in the dorsal root ganglia was identical in the three spinal segments and did not change between 10 and 24 weeks of gestation. This study provides the first demonstration of the low-affinity p75 nerve growth factor receptor immunoreactivity in the dorsal root ganglia from human fetuses at different gestational ages.