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)

The effects of wire grates on nerve injury and recovery were examined in rats housed in cages with sawdust-covered solid flooring. For the first 3 weeks of the study, 20 rats were housed on sawdust alone and 20 rats were housed in cages with wire grates placed over the sawdust. For the remaining 9 weeks, 10 animals housed on sawdust had wire grates added to their cages, while grates were removed from the cages of 10 animals. The effects of tactile stimulation on hindpaw plantar skin was measured weekly using the Von Frey filament test. Intraepidermal innervation using PGP 9.5 immunostaining and plantar nerve histology were assessed at the end of the 12-week study. After just 1 week on grates, hindpaw withdrawal thresholds were already markedly decreased and remained low until the grates were removed at 3 weeks. Thresholds returned to normal by 4 weeks after removal of the grates. Wire grates also induced increases in PGP 9.5 immunoreactive intraepidermal fine nerve endings that were normalized after grate removal. Demyelination, Wallerian degeneration and Renaut bodies were induced in the medial plantar nerve in rats housed in cages with wire-grate flooring. Nerve injury was largely resolved after 9 weeks on sawdust flooring. These data demonstrate that wire grates rapidly induce hindpaw tactile hyperesthesia and plantar neuropathy in rats and emphasize a risk of using wire-grate cage flooring in studies assessing hindlimb function and structure.
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PMID:Tactile hyperesthesia, altered epidermal innervation and plantar nerve injury in the hindfeet of rats housed on wire grates. 955 36

To determine whether ATP and P2X3 receptors contribute to bone-cancer pain in a mouse model, immunohistochemical techniques were used to identify whether changes in the labeling of P2X3 receptors on epidermal nerve fibers (ENFs) occurred during tumor development. C3H mice were injected with osteolytic fibrosarcoma cells in and around the calcaneus bone. These mice exhibited mechanical hyperalgesia by day 10 post-implantation as assessed using von Frey monofilaments. Biopsies of the plantar skin overlying the tumor were obtained at days 10, 14, and 18 post-implantation. Confocal images were analyzed for the number of PGP 9.5, P2X3, and CGRP immunoreactive (ir) ENFs. The overall ENF population (PGP-ir) decreased progressively over time, whereas the subsets of P2X3-ir fibers demonstrated a modest increase and CGRP-ir nerve fibers remained fairly constant. Importantly, the proportion of CGRP-ir fibers that labeled for P2X3 increased from approximately 6% in control animals to nearly 30% at day 14 following tumor cell implantation. These studies demonstrate increased expression of P2X3 receptors on CGRP-ir ENFs during tumor growth and suggest a role for ATP in cancer-related pain.
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PMID:Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. 1588 18

The acid sensing ion channel 3 (ASIC3) is critical for the development of secondary hyperalgesia as measured by mechanical stimulation of the paw following muscle insult. We designed experiments to test whether ASIC3 was necessary for the development of both primary and secondary mechanical hyperalgesia that develops after joint inflammation. We used ASIC3 -/- mice and examined the primary (response to tweezers) and secondary hyperalgesia (von-Frey filaments) that develops after joint inflammation comparing to ASIC3 +/+ mice. We also examined the localization of ASIC3 to the knee joint afferents innervating the synovium using immunohistochemical techniques before and after joint inflammation. We show that secondary mechanical hyperalgesia does not develop in ASIC3 -/- mice. However, the primary mechanical hyperalgesia of the inflamed knee joint still develops in ASIC3 -/- mice and is similar to ASIC3 +/+ mice. In knee joint synovium from ASIC3 +/+ mice without joint inflammation, ASIC3 was not localized to joint afferents that were stained with an antibody to protein gene product (PGP) 9.5 or calcitonin gene-related peptide (CGRP). ASIC3 was found, however, in synoviocytes of the knee joint of uninflamed mice. In ASIC3 +/+ mice with joint inflammation, ASIC3 co-localized with PGP 9.5 or CGRP in joint afferents innervating the synovium. We conclude that the decreased pH that occurs after inflammation would activate ASIC3 on primary afferent fibers innervating the knee joint, increasing the input to the spinal cord resulting in central sensitization manifested behaviorally as secondary hyperalgesia of the paw.
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PMID:Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice. 1834 37

Skin biopsies from patients with neuropathic pain often show changes in epidermal innervation, although it remains to be elucidated to what extent such changes can be linked to a particular subgroup of nerve fibers and how these changes are correlated with pain intensity. Here, we investigated to what extent behavioral signs of hyperalgesia are correlated with immunohistochemical changes of peptidergic and non-peptidergic epidermal nerve fibers in a rat model of nerve injury-induced pain. Rats subjected to unilateral partial ligation of the sciatic nerve developed significant mechanical and thermal hyperalgesia as tested by the withdrawal responses of the ipsilateral footpad to von Frey hairs and hotplate stimulation. At day 14, epidermal nerve fiber density and total epidermal nerve fiber length/mm2 were significantly and consistently reduced compared to the contralateral side, following testing and re-testing by two blinded observers. The expression of calcitonin gene-related peptide, a marker for peptidergic nerve fibers, was not significantly changed on the ipsilateral side. In contrast, the expression of the P2X3 receptor, a marker for non-peptidergic nerve fibers, was not only significantly reduced but could also be correlated with behavioral hyperalgesia. When labeling both peptidergic and non-peptidergic nerve fibers with the pan-neuronal marker PGP9.5, the expression was significantly reduced, albeit without a significant correlation with behavioral hyperalgesia. In conjunction, our data suggest that the pathology of the P2X3 epidermal nerve fibers can be selectively linked to neuropathy, highlighting the possibility that it is the degeneration of these fibers that drives hyperalgesia.
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PMID:The reduction of intraepidermal P2X3 nerve fiber density correlates with behavioral hyperalgesia in a rat model of nerve injury-induced pain. 2881 99

Low back pain (LBP) is associated with both axial discomfort and radiating leg pain. Although intervertebral discs are suspected as the source of pain in some individuals, the relationship between disc degeneration and back pain remains controversial. The goals of this study were to investigate the long-term impact of L4/L5 disc puncture on disc degeneration and the subsequent emergence, persistence, and underlying mechanisms of axial and radiating LBP in mice. L4 to L5 discs were punctured on the ventral aspect with a 30 gauge needle in 3-month old female CD1 mice, and the development of behavioral signs of axial discomfort (tail suspension and grip force), radiating hypersensitivity (von Frey and acetone), and motor impairment (rotarod) were monitored. Disc degeneration was assessed using X-ray, T2-magnetic resonance imaging, and histology, and persisted for up to 1 year. Innervation was quantified by immunohistochemistry using the pan-neuronal marker PGP9.5. Behavioural signs of axial discomfort peaked 3 to 9 months after injury. During the peak, local nerve density was increased. A transient increase in hypersensitivity to cold, suggestive of radiating pain, was observed 2 weeks after injury. Radiating pain then reemerged 9 to 12 months after injury in half the animals and correlated with increased dorsal innervation and reduced disc height at these late time points. In summary, a single-level disc injury is sufficient to induce prolonged disc degeneration and delayed axial and radiating pain. This model will be useful to investigate underlying mechanisms and potential therapeutic strategies for discogenic LBP.
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PMID:Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice. 2979 12

Chronic nerve compression (CNC) neuropathy is a common disease in the clinic and provokes paraesthesia, or numbness at early stage. The changes in muscle fiber composition and motor nerve terminal morphology in distal muscles were studied in this study. A well-established CNC model was used to assess the changes in the muscles. Behaviors were measured by von Frey filament test. The myosin heavy chain isoforms and neuromuscular junctions (NMJs) were stained by immunofluorescence to show the muscle fiber types composition and motor nerve terminals morphologic changes in the flexor digitorum longus (FDL) and lumbrical muscle. The fiber cross-sectional areas of different muscle fiber types were measured. The small-fiber degeneration of cutaneous nerve fibers was examined by detecting the protein gene product 9.5 (PGP9.5) with immunofluorescence. At 2nd month after compression, the proportion of type I and type II B fibers was markedly decreased, and that of type II A fibers was increased in the lumbrical muscle. There was no significant change in composition of muscle fiber types in FDL and NMJ morphology of FDL and lumbrical muscles. Intra-epidermal nerve fibre density (IENFD) declined at 2nd month after the compression. Our study reveals the morphological changes of the FDL and lumbrical muscle at an early stage of CNC. These findings may be helpful to understand muscle damage and pathophysiological development of the nerve compression, and provide new evidence for early treatment of CNC.
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PMID:Muscle Fiber Type Changes in Lumbrical Muscles at Early Stages of Chronic Nerve Compression. 3086 92