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Primary Afferents (primary + afferent)
Terms modified by Primary Afferents Selected AbstractsInhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout miceEXPERIMENTAL DERMATOLOGY, Issue 3 2005M. Seike Abstract:, A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (,/,) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (,/,) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (,/,) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn. [source] Functional characterization of prostaglandin F2, receptor in the spinal cord for tactile pain (allodynia)JOURNAL OF NEUROCHEMISTRY, Issue 2 2003Tadatoshi Muratani Abstract Prostaglandin F2, (PGF2,) binds to its receptor (FP) to increase the intracellular-free calcium concentration ([Ca2+]i) by coupling of FP with Gq protein. Spinal intrathecal administration of PGF2, to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent A,-fibres and N -methyl- d -aspartate receptor ,4 subunit are involved. FP in the spinal cord, however, was not well characterized. Here, we showed constitutive expression of FP mRNA in mouse spinal cord, and functionally characterized spinal FP-expressing cells which were involved in PGF2, -induced mechanical allodynia. The method for repetitive administration of oligodeoxyribonucleotides through tubing to conscious mice was established for mechanical allodynia evaluation. We identified an antisense oligodeoxyribonucleotide targeting FP mRNA, causing both disappearance of PGF2, -induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF2, rapidly increased [Ca2+]i of the cells in the deeper layer of the dorsal horn. In contrast, when the FP antisense oligodeoxyribonucleotide was repeatedly administered, the population of PGF2, -responsive cells in the slices reduced, and PGF2, -induced [Ca2+]i increase of these cells diminished. These data strongly suggested that, in the dorsal horn of the spinal cord, there are the FP-expressing cells which are involved in PGF2, -induced mechanical allodynia. [source] Neural mechanisms of cutaneous nociceptive pain. (Department of Neurology, University of Würzburg, Germany) Clin J Pain 2000;16:S131,S138.PAIN PRACTICE, Issue 2 2001Martin Koltzenburg: Acute mechanical, thermal, and chemically induced pains in the skin are signaled by a set of specific nociceptive afferents, which encode the magnitude of the perceived pain by their discharge intensity. After tissue injury or inflammation, a number of changes in their properties of the primary afferent occur parallel to profound changes in the central nervous system. Primary hyperalgesia (within the area of tissue injury) is best explained by changes of the properties of primary nociceptive afferents, whereas secondary hyperalgesia (increased pain sensitivity outside the area of tissue injury) critically requires functional changes in the central nervous system. Collectively, these changes are the basis for many forms of hyperalgesia that can present clinically as incident pain. Knowledge of the various types of hyperalgesia and their underlying mechanisms is required for better treatment of this challenging aspect of chronic pain. [source] T-type calcium channels: an emerging therapeutic target for the treatment of painDRUG DEVELOPMENT RESEARCH, Issue 4 2006Terrance P. Snutch Abstract It has become generally accepted that presynaptic high voltage,activated N-type calcium channels located in the spinal dorsal horn are a validated clinical target for therapeutic interventions associated with severe intractable pain. Low voltage,activated (T-type) calcium channels play a number of critical roles in nervous system function, including controlling thalamocortical bursting behaviours and the generation of spike wave discharges associated with slow wave sleep patterns. There is a growing body of evidence that T-type calcium channels also contribute in several ways to both acute and neuropathic nociceptive behaviours. In the one instance, the Cav3.1 T-type channel isoform likely contributes an anti-nociceptive function in thalamocortical central signalling, possibly through the activation of inhibitory nRT neurons. In another instance, the Cav3.2 T-type calcium channel subtype acts at the level of primary afferents in a strongly pro-nociceptive manner in both acute and neuropathic models. While a number of classes of existing clinical agents non-selectively block T-type calcium channels, there are no subtype-specific drugs yet available. The development of agents selectively targeting peripheral Cav3.2 T-type calcium channels may represent an attractive new avenue for therapeutic intervention. Drug Dev. Res. 67:404,415, 2006. © 2006 Wiley-Liss, Inc. [source] Cocaine- and amphetamine-regulated transcript peptide (CART) is present in peptidergic C primary afferents and axons of excitatory interneurons with a possible role in nociception in the superficial laminae of the rat spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Márk Kozsurek Abstract Cocaine- and amphetamine-regulated transcript peptides (CART) have been implicated in the regulation of several physiological functions, including pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. In this study, we used antibody against CART peptide, together with markers for various types of primary afferents, interneurons and descending systems to determine the origin of the CART-immunoreactive axons in the superficial laminae of the rat spinal cord. Calcitonin gene-related peptide (CGRP), a marker for peptidergic primary afferents in the dorsal horn, was present in 72.6% and 34.8% of CART-immunoreactive axons in lamina I and II, respectively. The majority of these fibres also contained substance P (SP), while a few were somatostatin (SOM)-positive. The other subpopulation of CART-immunoreactive boutons in lamina I and II also expressed SP and/or SOM without CGRP, but contained vesicular glutamate transporter 2, which is present mainly in excitatory interneuronal terminals. Our data demonstrate that the majority of CART-immunoreactive axons in the spinal dorsal horn originate from peptidergic nociceptive primary afferents, while the rest arise from excitatory interneurons that contain SP or SOM. This strongly suggests that CART peptide can affect glutamatergic neurotransmission as well as the release and effects of SP and SOM in nociception and other sensory processes. [source] Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Dorte X. Gram Abstract The system that regulates insulin secretion from ,-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus. [source] The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal hornEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003A. J. Todd Abstract Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94,100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III,VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter. [source] Afferent ingrowth and onset of activity in the rat trigeminal nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000P. M. E. Waite Abstract A novel in vitro preparation, consisting of the rat brainstem with the trigeminal ganglion attached, has been used to study the anatomical and functional development of the trigeminal nucleus from embryonic day (E)13 to postnatal day (P)6. Neurobiotin injections into the trigeminal ganglion showed that primary afferents had reached the trigeminal tract by E13 and had grown simple, mainly unbranched, collaterals into all levels of the nucleus by E15. By E17, these collaterals were extensively branched, with occasional boutons present. Patches of intense neurobiotin-labelled terminals, corresponding to whisker-related patterns, were first seen at E20 and became clearer over the next few days. Terminal arbours at this stage were relatively localized and densely branched, with many boutons. Responses from the trigeminal nucleus were recorded with suction electrodes, following stimulation of the trigeminal ganglion. Recordings from the main sensory nucleus showed a postsynaptic response was first present at E15. At E16, bath application of AP5 and DNQX showed that the response contained both NMDA and AMPA components, with NMDA predominating (75%). The NMDA : AMPA ratio remained high until P1, then gradually declined to 50% by P6. The postsynaptic response was also reduced by bath application of bicuculline, indicating the presence of a GABAA -mediated excitatory component. GABAergic excitation was present at all ages but was maximal from E20 to P1, the age at which whisker-related patterns are developing. It is hypothesized that both GABAergic excitation and NMDA receptor activation play a role in the consolidation of trigeminal connections, and are thus important in the development of whisker-related patterns. [source] From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory systemJOURNAL OF ANATOMY, Issue 2 2007I. Tavares Abstract The endogenous pain modulatory system is a complex network of brain areas that control nociceptive transmission at the spinal cord by inhibitory and facilitatory actions. The balance between these actions ensures effective modulation of acute pain, while during chronic pain the pronociceptive effects appear to prevail. The mechanisms underlying this imbalance were studied as to the role of two medullary components of the pain modulatory system: the dorsal reticular nucleus and the caudal ventrolateral medulla, which function primarily as pronociceptive and antinociceptive centres, respectively. Both areas are connected with the spinal dorsal horn by closed reciprocal loops. In the spino-dorsal reticular nucleus loop, the ascending branch is strongly inhibited by spinal GABAergic neurons, which may act as a buffering system of the dorsal reticular nucleus-centred amplifying effect. In the spino-caudal ventrolateral medulla loop, the ascending branch is under potent excitation of substance P (SP) released from primary afferents, which is likely to trigger the intense descending inhibition detected in acute pain. During chronic pain, the activity in the lateral reticular formation of the caudal ventrolateral medulla changes, so that the action of the caudal ventrolateral medulla upon SP-responsive spinal neurons shifts from inhibitory to excitatory. The mechanisms of this modulatory shift are unknown but probably relate to the decresed expression of µ-opioid, ,-opioid and GABAB receptors. Normalizing receptor expression in the caudal ventrolateral medulla or controlling noci-evoked activity at the dorsal reticular nucleus or caudal ventrolateral medulla by interfering with neurotransmitter release is now possible by the use of gene therapy, an approach that stands out as a unique tool to manipulate the supraspinal endogenous pain control system. [source] The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal hornJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Hong-Yi Zhou Abstract The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord. [source] Immunohistochemical and hodological characterization of calbindin-D28k-containing neurons in the spinal cord of the turtle, Pseudemys scripta elegansMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2007Ruth Morona Abstract Neurons and fibers containing the calcium-binding protein calbindin-D28k (CB) were studied by immunohistochemical techniques in the spinal cord of adult and juvenile turtles, Pseudemys scripta elegans. Abundant cell bodies and fibers immunoreactive for CB were widely and distinctly distributed throughout the spinal cord. Most neurons and fibers were labeled in the superficial dorsal horn, but numerous cells were also located in the intermediate gray and ventral horn. In the dorsal horn, most CB-containing cells were located in close relation to the synaptic fields formed by primary afferents, which were not labeled for CB. Double immunohistofluorescence demonstrated distinct cell populations in the dorsal horn labeled only for CB or nitric oxide synthase, whereas in the dorsal part of the ventral horn colocalization of nitric oxide synthase was found in about 6% of the CB-immunoreactive cells in this region. Choline acetyltransferase immunohistochemistry revealed that only about 2% of the neurons in the dorsal part of the ventral horn colocalized CB, whereas motoneurons were not CB-immunoreactive. The involvement of CB-containing neurons in ascending spinal projections to the thalamus, tegmentum, and reticular formation was demonstrated combining the retrograde transport of dextran amines and immunohistochemistry. Similar experiments demonstrated supraspinal projections from CB-containing cells mainly located in the reticular formation but also in the thalamus and the vestibular nucleus. The revealed organization of the neurons and fibers containing CB in the spinal cord of the turtle shares distribution and developmental features, colocalization with other neuronal markers, and connectivity with other tetrapods and, in particular with mammals. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] Differential dye coupling reveals lateral giant escape circuit in crayfishTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2003Brian L. Antonsen Abstract The lateral giant (LG) escape circuit of crayfish mediates a coordinated escape triggered by strong attack to the abdomen. The LG circuit is one of the best understood of small systems, but models of the circuit have mostly been limited to simple ball-and-stick representations, which ignore anatomical details of contacts between circuit elements. Many of the these contacts are electrical; here we use differential dye coupling, a technique which could help reveal connection patterns in many neural circuits, to reveal in detail the circuit within the terminal abdominal ganglion. Sensory input from the tailfan forms a somatotopic map on the projecting LG dendrites, which together with interafferent coupling mediates a lateral excitatory network that selectively amplifies strong, phasic, converging input to LG. Mechanosensory interneurons contact LG at sites distinct from the primary afferents and so maximize their summated effect on LG. Motor neurons and premotor interneurons are excited near the initial segments of the LGs and innervate muscles for generating uropod flaring and telson flexion. Previous research has shown that spatial patterns of input are important for signal integration in LG; this map of electrical contact points will help us to understand synaptic processing in this system. J. Comp. Neurol. 466:1,13, 2003. © 2003 Wiley-Liss, Inc. [source] Pre- and postsynaptic modulation of monosynaptic reflex by GABAA receptors on turtle spinal cordTHE JOURNAL OF PHYSIOLOGY, Issue 14 2010Wendy Bautista There is growing evidence that activation of high affinity extrasynaptic GABAA receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABAA receptors mediating tonic inhibition participate in the modulation of monosynaptic reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a dorsal root depressed the test monosynaptic reflex (MSR) at long condition,test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABAA as it was completely blocked by 20 ,m picrotoxin (PTX) or bicuculline (BIC) or 1 ,m gabazine, simultaneously depressing the dorsal root potential (DRP) without MSR facilitation. Interestingly 100 ,m picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABAA receptors, affects receptor subtypes with ,4/6 subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of ,4/6 GABAA receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABAA mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABAA receptors located at the motoneurones and primary afferents might produce tonic inhibition of monosynaptic reflex, and (3) GABAA receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation. [source] Serotonin 5-HT2 receptor activation induces a long-lasting amplification of spinal reflex actions in the ratTHE JOURNAL OF PHYSIOLOGY, Issue 1 2001D. W. Machacek 1C-fibre activation induces a long-term potentiation (LTP) in the spinal flexion reflex in mammals, presumably to provide enhanced reflexive protection of damaged tissue from further injury. Descending monoaminergic pathways are thought to depress sensory input but may also amplify spinal reflexes; the mechanisms of this modulation within the spinal cord remain to be elucidated. 2We used electrical stimulation of primary afferents and recordings of motor output, in the rat lumbar spinal cord maintained in vitro, to demonstrate that serotonin is capable of inducing a long-lasting increase in reflex strength at all ages examined (postnatal days 2,12). 3Pharmacological analyses indicated an essential requirement for activation of 5-HT2C receptors while 5-HT1A/1B, 5-HT7 and 5-HT2A receptor activation was not required. In addition, primary afferent-evoked synaptic potentials recorded in a subpopulation of laminae III-VI spinal neurons were similarly facilitated by 5-HT. Thus, serotonin receptor-evoked facilitatory actions are complex, and may involve alterations in neuronal properties at both motoneuronal and pre-motoneuronal levels. 4This study provides the first demonstration of a descending transmitter producing a long-lasting amplification in reflex strength, accomplished by activating a specific serotonin receptor subtype. It is suggested that brain modulatory systems regulate reflex pathways to function within an appropriate range of sensori-motor gain, facilitating reflexes in behavioural situations requiring increased sensory responsiveness. [source] | |||||||||||||||||||||||||