Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A total of 758 fibers were isolated from previously transected and repaired ulnar nerves of five baboons. These fibers were compared to fibers from normal and previously crushed nerves studied in an earlier experiment. 2. The conduction velocities of the proximal portion of the injured axons dropped below normal, and this reduction persisted until reinnervation appeared nearly complete. 3. The receptive-field organization and response characteristics of 79 cutaneous afferent fibers serving the glabrous skin were studied in detail and compared to cutaneous afferent fibers of normal and previously crushed nerves studied earlier. 4. Initially, receptive fields were small and irregular, and often one fiber served several distinct skin regions. Ten months later, most of these abnormalities were no longer apparent. 5. Thresholds for single impulses elicited by von Frey hairs remained elevated for up to 4 mo after the receptive field reappeared, but then dropped abruptly to a near-normal range. 6. After reinnervation, rapidly adapting fibers displayed tuning curves characteristic of their submodality, but thresholds were elevated and only began to approach the normal range 6 mo after reinnervation. 7. After reinnervation, slowly adapting fibers displayed stimulus-response curves with elevated thresholds and they tended to saturate at lower stimulus intensities than normal fibers. 8. When compared to the return of function following a crushing injury, axons that had been transected displayed a slower time course for the return to normal values of conduction velocity and threshold. Receptive-field organization also remained abnormal for a longer time period. 9. These data support the hypotheses that a) breaking the continuity of the Schwann cells and extracellular matrix that occurs during transection but not during crush is a major factor leading to errors of axonal regeneration in the distal stump, b) submodality specificity is a property of the regenerating axon, and c) regenerating axons are influenced by an internal or external cue, causing them to form and maintain a single relatively homogeneous receptive field.
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PMID:Reinnervation of glabrous skin in baboons: properties of cutaneous mechanoreceptors subsequent to nerve transection. 745 27

1. The effect of the calcium channel antagonist diltiazem on pH-induced sustained nociceptor excitation was investigated in a rat skin-saphenous nerve preparation, in vitro, where receptive fields of identified and isolated single fibers were superfused at the corium side with controlled solutions to assess their chemosensitivity. 2. Unmyelinated mechano-heat sensitive ("polymodal") C fiber terminals (n = 78) were superfused with a CO2-saturated synthetic interstitial fluid (CO2-SIF, pH 6.1). Fibers responding to this acid pH condition (n = 60; 77%) were further stimulated for > or = 30 min and additionally treated with diltiazem in various concentrations (10(-6)-10(-3) M) during the middle 10-min period. Usually only one concentration of diltiazem was applied per fiber, although in some cases diltiazem was applied repeatedly and in increasing concentrations. 3. Diltiazem dose-dependently and reversibly reduced the pH-induced sustained nociceptor discharge to a significant degree or completely abolished it. With higher concentrations, both the relative number of units affected and the average amount of suppression were enhanced. The half-maximal blocking concentration (IC50) was estimated to 1.1.10(-4) M diltiazem, the half-maximal concentration for gradual suppression of the pH response was 2.10(-5) M diltiazem. 4. Also, the delay of onset of the suppressive effect decreased with higher diltiazem concentrations. After diltiazem, a partial recovery of the pH-induced discharge was achieved within 10 min depending on the degree of suppression. 5. Before, after, and sometimes during the superfusion, the mechanical (von Frey) thresholds were determined and found to be significantly increased after partial wash out of diltiazem (10(-4) and 10(-3) M; P < 0.006 and P < 0.008, respectively). After 10(-3) M diltiazem superfusion (and 10 min of wash-out), the responsiveness to mechanical stimulation of the majority of the fibers was still totally lost. 6. Heat thresholds were still found to be significantly increased after treatment with diltiazem at 10(-3) and 10(-4) M concentrations (and 10 min of wash out), but appeared unchanged after wash out of lower concentrations. 7. In five mechano-heat-sensitive C fibers, electrical stimulation via a microelectrode placed in the receptive field was used to demonstrate a diltiazem-dose-dependent (10(-5), 10(-4), 10(-3) M) progressive retardation of the nerve conduction velocity and an increase of the electrical threshold. Superfusion for 6 min of diltiazem 10(-5) M was sufficient to block axonal conduction as well as mechanosensitivity, which both recovered synchronously during wash out. 8. It can be concluded from the results that the suppressive effect of diltiazem on pH-induced nociceptor excitation can be explained by a use-dependent axonal block, comparable with the action of local anesthetics and affecting all modalities of sensory responsiveness. 9. The findings provide no indication that a transformed calcium channel specifically sensitive to diltiazem is involved in pH-induced sustained nociceptor excitation.
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PMID:Diltiazem blocks the PH-induced excitation of rat nociceptors together with their mechanical and electrical excitability in vitro. 882 37

Tight ligation and transection of the L5 spinal nerve (SNL) gives rise to pain which is dependent upon activity in the sympathetic nervous system. It also results in novel adrenergic sympathetic innervation of the dorsal root ganglion (DRG) with the formation of pericellular axonal basket structures around some DRG neurons. Since the sympathetic sprouting and basket formation may represent an anatomical basis for pain-generating interactions between the sympathetic efferent neurons and sensory afferent neurons, it is of great interest to determine possible chemical mediators of this phenomenon. Previous findings have shown that IL-6 can contribute to sympathetically-independent pain, and can give rise to thermal hyperalgesia when injected intrathecally. We have now investigated a possible contributory role of the pleiotropic cytokine interleukin-6 (IL-6) in sympathetically-mediated pain: we gave IL-6 knockout mice and mice of the parent strain c57B6/129 a SNL, assessed their resulting pain behavior for 10 days post-surgery, and used tyrosine-hydroxylase immunohistochemistry to compare sympathetic sprouting in the DRG at the end of the testing period. We found that thermal allodynia (as assessed by measuring the latency to withdrawal from radiant heat) did not differ significantly between strains. On the other hand, in the IL-6 mice, mechanoallodynia (as assessed with von Frey filaments) was markedly delayed. Sympathetic invasion of the fiber tract and cell layer of the DRG, and the formation of pericellular axonal baskets were all significantly reduced in the IL-6 knockout mice compared to the control strain. These results imply a facilitatory role for IL-6 in pain and sympathetic sprouting induced by nerve injury, and add to the growing list of roles for IL-6 in neuropathological events.
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PMID:Spinal nerve lesion-induced mechanoallodynia and adrenergic sprouting in sensory ganglia are attenuated in interleukin-6 knockout mice. 983 21

A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5 <c.v.<5 m/s) and 13% (2/15) of C units (c.v. </=1.5 m/s). The mean TTX concentration that produced complete suppression of mechanoresponsiveness was approximately 270-fold higher in C units than in fast A-delta units. In contrast, no significant difference was found between C and A-delta units in the concentration of lidocaine required for complete suppression of mechanoresponsiveness, indicating that the greater TTX resistance of mechanoresponsiveness in C units is not attributable to differences in safety factor unrelated to channel subtype. These data offer indirect evidence that a TTX-resistant channel subtype is expressed in the terminal axonal branches of many of the more slowly conducting (C and slow A-delta) dural afferents. The channel appears to be present in these fibers, but not in the faster A-delta fibers, in sufficient numbers to support the initiation and propagation of mechanically induced impulses. Comparison with previous data on the absence of TTX resistance in peripheral nerve fibers suggests that the TTX-resistant sodium channel may be a distinctive feature of the receptive rather than the conductive portion of the sensory neuron's axonal membrane.
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PMID:Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers. 1003 48

A mouse model of neuropathic pain was developed by a photochemically induced ischemic nerve injury in normal male C57/BL6 mice. The ischemia was induced by unilateral irradiation of the sciatic nerve with an argon ion laser after intravenous administration of a photosensitizing dye, erythrosin B. The nerve injury resulted in a significant decrease in withdrawal threshold of the hindpaws to mechanical stimulation with von Frey hairs, as well as increased responsiveness to cold and heat stimulation. The mice, however, did not exhibit overt spontaneous pain-like behaviors. The evoked pain-related behaviors were observed bilaterally, although the ipsilateral changes were greater than on the contralateral side. The extent and time course of the behavioral changes were related to the duration of laser irradiation, with 1-min exposure producing the most consistent effect. Morphological examination at the light microscopic level revealed partial demyelination and axonal degeneration of the large myelinated fibers at the epicenter of the lesion 1 week postirradiation. The extent of the damage was correlated with the duration of irradiation. Injury and loss of unmyelinated fibers were also observed at the electronmicroscopic level. We conclude that an intravascular photochemical reaction leading to ischemia results in graded damage to the sciatic nerve in mice. Moreover, the nerve injury is associated with the development of abnormal pain-related behaviors. Both the behavioral and the morphological changes are correlated with the duration of irradiation. These results establish a mouse model of partial nerve injury with neuropathic pain-like behaviors which may be useful in studies using genetically modified mice.
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PMID:Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve. 1078 62

The present experiments investigated the behavioral and immunocytchemical (ICC) effects of applying complete Freund's adjuvant (CFA) to the orbital portion of the infraorbital nerve (IOn). Two control groups, the first had saline applied to the IOn and the second underwent sham operation, were included in the study. In the CFA group, significant hyper-responsiveness to von Frey (analysis of variance <0.05) and to pinprick stimulation (Kruskal Wallis <0.05) in the vibrissal pad was observed on the fourth and the fifth days post-operative (dpo). This was accompanied by a reduced bite force and altered bite patterns of similar duration. Histology of the IOn in CFA rats revealed immune cell infiltration and edema around and in the nerve trunk with only mild axonal damage confirmed by neuropeptide Y immunoreactivity in trigeminal ganglion. Histological areas of inconsistent and mild inflammation were observed in the saline group that were accompanied by similarly attenuated behavioral and ICC changes. This model of inflammation-induced neuropathic pain is highly applicable to the study of neuroinflammatory orofacial pain.
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PMID:Application of a pro-inflammatory agent to the orbital portion of the rat infraorbital nerve induces changes indicative of ongoing trigeminal pain. 1240 33

Delivery of neurotrophic factors in acute models of spinal cord injury in adult rats can rescue axotomized neurons, promote axonal growth, and partially restore function. The extent to which repair and recovery of function can be achieved after chronic injury has received less attention. In the companion paper we show that transplanting fibroblasts genetically modified to produce neurotrophic factors into chronic (6-week) hemisection injuries results in sprouting, partial neuroprotection, but only limited regeneration. Here we describe functional consequences of this treatment using a series of behavioral tests. Adult rats received a complete unilateral C3/C4 hemisection and recovery from the injury was assessed over 5 weeks. At 6 weeks postoperative, the experimental group received grafts of a combination of fibroblasts modified to secrete BDNF or NT-3. The operated control groups received grafts of either gelfoam or gelfoam with fibroblasts expressing GFP into the lesion site. Behavioral recovery in the three groups was assessed over the next 10 weeks. Severe deficits with no recovery in any of the groups were observed in several tests (BBB, limb preference, narrow beam, horizontal rope test) that measure primarily motor function. Recovery was observed in the grid test, a measure of sensorimotor function, and the von Frey test, a measure of response to mechanical stimulation, but there were no differences between the operated control or experimental groups. Both groups also showed recovery from heat-induced hyperalgesia, with the experimental group exhibiting greater recovery than the operated control groups. In this test, delivery of neurotrophic factors from transplanted fibroblasts does not worsen responses to nociceptive stimuli and in fact appears to reduce hypersensitivity. Our data also demonstrate that additional damage to the spinal cord upon placement of a graft further compromises behavioral recovery for locomotor and postural function. Additional therapeutic interventions will be necessary to provide greater levels of recovery after chronic injuries.
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PMID:Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. 1463 85

Complete nerve transection results in loss of sensation and paralysis of the involved extremity. Such injury drastically reduces content of the nociceptive peptides, substance P, and somatostatin in the dorsal horn of the spinal cord and dorsal root ganglia innervating the limb. Partial nerve injuries occur more commonly in clinical practice, however, and frequently result in the development of chronic neuropathic pain. To investigate mechanisms underlying this pathologic pain syndrome, rats were subjected to partial sciatic nerve transection. Withdrawal thresholds determined with Von Frey hairs dropped dramatically in the operated limb. On postoperative Day 4, thresholds had decreased from 15 g to less than 5 g on the operated side, whereas those on the contralateral (unoperated) side or those from sham-operated rats did not change. Sciatic hemisection had no effect on total content of either substance P or somatostatin in the dorsal spinal cord and lumbar dorsal root ganglia as measured by radioimmunoassay on postoperative Days 4, 7, or 14. However, when examined immunohistochemically, there was a marked redistribution of both peptides associated with partial transection. On the contralateral side or in sham-operated rats, both substance P and somatostatin were confined to the superficial laminae of the dorsal horn. By contrast, on the operated side, content of both peptides was reduced by more than half in the superficial laminae. There was a compensatory increase in content in the deeper laminae where nociceptive peptides are not usually found. Redistribution of substance P and somatostatin may be due to axonal sprouting, increased peptide expression by interneurons, or aberrant expression of nociceptive peptides by neurons normally mediating mechanical sensation. The presence of increased levels of nociceptive peptides in regions of the spinal cord that mediate innocuous sensation may underlie development of allodynia.
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PMID:Partial sciatic nerve transection causes redistribution of pain-related peptides and lowers withdrawal threshold. 1524 43

Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo-A. Two neutralizing antibodies against Nogo-A were used to study recovery and axonal regeneration after spinal cord lesions. Three months old Lewis rats were tested in sensory-motor tasks (open field locomotion, crossing of ladder rungs and narrow beams, the CatWalk(R) runway, reactions to heat and von Frey hairs). A T-shaped lesion was made at T8, and an intrathecal catheter delivered highly purified anti-Nogo-A monoclonal IgGs or unspecific IgGs for 2 weeks. A better outcome in motor behavior was obtained as early as two weeks after lesion in the animals receiving the Nogo-A antibodies. Withdrawal responses to heat and mechanical stimuli were not different between the groups. Histology showed enhanced regeneration of corticospinal axons in the anti-Nogo-A antibody groups. fMRI revealed significant cortical responses to stimulation of the hindpaw exclusively in anti-Nogo-A animals. These results demonstrate that neutralization of the neurite growth inhibitor Nogo-A by intrathecal antibodies leads to enhanced regeneration and reorganization of the injured CNS, resulting in improved recovery of compromised functions in the absence of dysfunctions.
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PMID:Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. 1617 73

Serotonin immunoreactive (5-HT-IR) neurons identified as cerebropleural ganglion triplets (CPTs) in Hermissenda may be homologues of 5-HT-IR neurons identified in other opisthobranch molluscs. In studies of isolated nervous systems and semi-intact preparations we used a combination of immunohistochemical techniques and fluorescent labeling with Lucifer yellow to identify 5-HT-IR CPT neurons after investigating sensory inputs and motor neuron projections. Here we show that identified 5-HT-IR CPT interneurons receive sensory input from mechanoreceptors and photoreceptors. In semi-intact preparations with intact pedal nerves P1 and P2, cutaneous stimulation of the middle or tail regions of the foot with calibrated von Frey hairs elicited spikes recorded from identified CPT interneurons. Illumination of the eyes evoked a small complex excitatory postsynaptic potential (EPSP) and resulted in a modest increase in the spike discharge of CPT interneurons. Immunostaining of Lucifer yellow-labeled neurons revealed that CPT interneurons projected an axonal process to the contralateral pedal ganglion. Depolarization of CPT interneurons with extrinsic current evoked EPSPs and spikes recorded from identified VP2 pedal neurons, motor neurons previously shown to elicit movement of the anterior foot. Extrinsic current stimulation of CPT interneurons in semi-intact preparations evoked movement of the anterior foot but did not facilitate ciliary activity or evoke PSPs recorded in identified VP1 ciliary motor neurons. Our results show that CPT neurons are polysensory interneurons that contribute to reflexive foot contractions in Hermissenda.
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PMID:Serotonin-immunoreactive CPT interneurons in Hermissenda: identification of sensory input and motor projections. 1664 89


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