The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform

Ismail Devecioglu - One of the best experts on this subject based on the ideXlab platform.

  • a novel vibrotactile system for stimulating the Glabrous Skin of awake freely behaving rats during operant conditioning
    Journal of Neuroscience Methods, 2015
    Co-Authors: Ismail Devecioglu, Burak Guclu
    Abstract:

    Abstract Background Rat Skin is innervated by mechanoreceptive fibers similar to those in other mammals. Tactile experiments with behaving rats mostly focus on the vibrissal system which does not exist in humans. The aim of this study was to design and implement a novel vibrotactile system to stimulate the Glabrous Skin of behaving rats during operant conditioning. New method A computer-controlled vibrotactile system was developed for various tasks in which the volar surface of unrestrained rats’ fore- and hindpaws was stimulated in an operant chamber. Results The operant chamber was built from off-the-shelf components. A highly accurate electrodynamic shaker with a novel multi-probe design was used for generating mechanical displacements. Twenty-five rats were trained for four sequential tasks: (A) middle-lever (trial start signal) press, (B) side-lever press with an associated visual cue, (C) similar to (B) with the addition of an auditory/tactile stimulus, (D) auditory/tactile detection (yes/no) task. Out of 9 rats which could complete the tactile version of this training schedule, 5 had over 70% accuracy in the tactile version of the detection task. Comparison with existing methods Unlike actuators for stimulating whiskers, this system does not require a particular head/body alignment and can be used with freely behaving animals. Conclusions The vibrotactile system was found to be effective for conditioning freely behaving rats based on stimuli applied on the Glabrous Skin. However, detection accuracies were lower compared to those in tasks involving whisker stimulation reported previously, probably due to differences in cortical processing.

  • asymmetric response properties of rapidly adapting mechanoreceptive fibers in the rat Glabrous Skin
    Somatosensory and Motor Research, 2013
    Co-Authors: Ismail Devecioglu, Burak Guclu
    Abstract:

    Previous histological and neurophysiological studies have shown that the innervation density of rapidly adapting (RA) mechanoreceptive fibers increases towards the fingertip. Since the psychophysical detection threshold depends on the contribution of several RA fibers, a high innervation density would imply lower thresholds. However, our previous human study showed that psychophysical detection thresholds for the Non-Pacinian I channel mediated by RA fibers do not improve towards the fingertip. By recording single-unit spike activity from rat RA fibers, here we tested the hypothesis that the responsiveness of RA fibers is asymmetric in the proximo-distal axis which may counterbalance the effects of innervation density. RA fibers (n = 32) innervating the digital Glabrous Skin of rat hind paw were stimulated with 40-Hz sinusoidal mechanical bursts at five different stimulus locations relative to the receptive field (RF) center (two distal, one RF center, two proximal). Different contactor sizes (area: 0.39,...

Burak Guclu - One of the best experts on this subject based on the ideXlab platform.

  • a novel vibrotactile system for stimulating the Glabrous Skin of awake freely behaving rats during operant conditioning
    Journal of Neuroscience Methods, 2015
    Co-Authors: Ismail Devecioglu, Burak Guclu
    Abstract:

    Abstract Background Rat Skin is innervated by mechanoreceptive fibers similar to those in other mammals. Tactile experiments with behaving rats mostly focus on the vibrissal system which does not exist in humans. The aim of this study was to design and implement a novel vibrotactile system to stimulate the Glabrous Skin of behaving rats during operant conditioning. New method A computer-controlled vibrotactile system was developed for various tasks in which the volar surface of unrestrained rats’ fore- and hindpaws was stimulated in an operant chamber. Results The operant chamber was built from off-the-shelf components. A highly accurate electrodynamic shaker with a novel multi-probe design was used for generating mechanical displacements. Twenty-five rats were trained for four sequential tasks: (A) middle-lever (trial start signal) press, (B) side-lever press with an associated visual cue, (C) similar to (B) with the addition of an auditory/tactile stimulus, (D) auditory/tactile detection (yes/no) task. Out of 9 rats which could complete the tactile version of this training schedule, 5 had over 70% accuracy in the tactile version of the detection task. Comparison with existing methods Unlike actuators for stimulating whiskers, this system does not require a particular head/body alignment and can be used with freely behaving animals. Conclusions The vibrotactile system was found to be effective for conditioning freely behaving rats based on stimuli applied on the Glabrous Skin. However, detection accuracies were lower compared to those in tasks involving whisker stimulation reported previously, probably due to differences in cortical processing.

  • asymmetric response properties of rapidly adapting mechanoreceptive fibers in the rat Glabrous Skin
    Somatosensory and Motor Research, 2013
    Co-Authors: Ismail Devecioglu, Burak Guclu
    Abstract:

    Previous histological and neurophysiological studies have shown that the innervation density of rapidly adapting (RA) mechanoreceptive fibers increases towards the fingertip. Since the psychophysical detection threshold depends on the contribution of several RA fibers, a high innervation density would imply lower thresholds. However, our previous human study showed that psychophysical detection thresholds for the Non-Pacinian I channel mediated by RA fibers do not improve towards the fingertip. By recording single-unit spike activity from rat RA fibers, here we tested the hypothesis that the responsiveness of RA fibers is asymmetric in the proximo-distal axis which may counterbalance the effects of innervation density. RA fibers (n = 32) innervating the digital Glabrous Skin of rat hind paw were stimulated with 40-Hz sinusoidal mechanical bursts at five different stimulus locations relative to the receptive field (RF) center (two distal, one RF center, two proximal). Different contactor sizes (area: 0.39,...

Fred J. Looft - One of the best experts on this subject based on the ideXlab platform.

Richard E Coggeshall - One of the best experts on this subject based on the ideXlab platform.

  • inflammation induced up regulation of neurokinin 1 receptors in rat Glabrous Skin
    Neuroscience Letters, 2002
    Co-Authors: Susan M Carlton, Richard E Coggeshall
    Abstract:

    Peripheral inflammation sensitizes primary afferent fibers causing lowered thresholds and increased responses to noxious input. One mechanism for sensitization might be increased expression of receptors whose activation results in nociceptor activity. Accordingly, the present study demonstrates that 15.6% of unmyelinated primary afferent axons in rat Glabrous Skin express the neurokinin 1 (NK1) receptor. At 48 h following hindpaw inflammation with complete Freund's adjuvant, the proportion of unmyelinated axons expressing NK1 receptors significantly increases to 23.6%. This implies a considerable upregulation of NK1 receptor synthesis in the dorsal root ganglia with subsequent transport to peripheral nociceptive terminals. Antagonizing peripheral NK1 receptors locally would be effective in reducing inflammatory pain by reducing neural transduction in NK1-expressing nociceptors as well as lessening the inflammatory vascular effects of peripheral substance P.

  • localization and activation of substance p receptors in unmyelinated axons of rat Glabrous Skin
    Brain Research, 1996
    Co-Authors: Susan M Carlton, Shengtai Zhou, Richard E Coggeshall
    Abstract:

    Abstract Immunohistochemical staining for the substance P (neurokinin 1, NK1) receptor labels 32% of the unmyelinated axons in the Glabrous Skin of the rat hindpaw. This is the first demonstration of substance P (SP) receptors associated with the membranes of primary afferent fibers. Injection of SP into the subcutaneous tissue of the third hind toe results in behavioral changes interpreted as mechanical hyperalgesia and mechanical allodynia. These nocifensive behaviors can be blocked by the NK1 antagonist CP99,994-1. The presence of peripheral axons immunolabelled for NK1 receptors and the demonstration that exogenous peripheral SP causes nocifensive behaviors would seem to indicate that SP can have a direct effect on sensory afferents with activation of these receptors resulting in fine afferent firing and thus the pain-related behaviors. Additionally, the presence of round, clear vesicles in some of the SP receptor-labelled axons suggests the presence of autoreceptors since it is known that many primary sensory afferents contain SP.

  • localization and activation of glutamate receptors in unmyelinated axons of rat Glabrous Skin
    Neuroscience Letters, 1995
    Co-Authors: Susan M Carlton, Gregory L Hargett, Richard E Coggeshall
    Abstract:

    Abstract Immunohistochemical staining for the glutamate receptor subtypes N -methyl- d -aspartate (NMDA), kainate, and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) results in a significant number of labeled unmyelinated axons in the Glabrous Skin of the rat hindpaw. Injection of glutamate into the rat hindpaw results in behavioral changes interpreted as mechanical allodynia and mechanical hyperalgesia. The anatomical findings provide a reasonable explanation for the action of the exogenous peripheral glutamate, namely that activation of these receptors leads to increased primary afferent activity in unmyelinated axons and thus to pain behaviors. AMPA receptors are frequently associated with small clear vesicles in the axoplasm of the unmyelinated axons, many of which have been previously shown to contain high concentrations of glutamate. This finding indicates that these might be autoreceptors and so glutamate itself might regulate certain types of peripheral impulse traffic. The presence of peripheral glutamate receptors associated with unmyelinated axons suggests the possibility that glutamate antagonists applied peripherally might prevent or attenuate some pain-related behaviors.

Susan M Carlton - One of the best experts on this subject based on the ideXlab platform.

  • Glutamate-induced excitation and sensitization of nociceptors in rat Glabrous Skin.
    Pain, 2020
    Co-Authors: Junhui Du, M Koltzenburg, Susan M Carlton
    Abstract:

    Anatomical studies demonstrate the presence of glutamate receptors on unmyelinated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the Glabrous Skin results in nociceptive behaviors. The present study describes a novel in vitro Skin-nerve preparation using the Glabrous Skin from the rat hindpaw. In the first series of experiments, recordings were obtained from 141 fibers that responded to a strong mechanical search stimulus. Based on their conduction velocity they were classified as C (27%), A delta (28%) and A beta (45%) fibers. The C and A delta fibers typically exhibited sustained firing during suprathreshold mechanical stimuli whereas both rapidly (66%) and slowly (34%) adapting responses were obtained from A beta fibers. Noxious heat excited 46% of the C fibers but only 12% of the A delta units. In another series of experiments application of an ascending series of glutamate concentrations (10, 100, 300, and 1000 microM) to A delta (n=14) and C (n=19) nociceptors resulted in a significant excitation of 43% (6/14) A delta fibers and 68% (13/19) C fibers. At these concentrations, there was no excitation of A beta units (n=13). Superfusion of the receptive fields of either mechanoheat-sensitive A (AMH, n=10) or C fibers (CMH, n=12) for 2 min with 300 microM glutamate resulted in sensitization of 90% (9/10) AMH and 92% (11/12) CMH fibers to subsequent thermal stimulation. This was evidenced by a significant (1) decrease in thermal threshold for activation, (2) increase in discharge rate, and (3) increase in peak instantaneous frequencies during the second heat trial. Glutamate-induced sensitization to heat occurred in the absence of either a glutamate-induced excitation or an initial heat response. Exposure of A delta or C fibers to glutamate did not result in a decrease in von Frey thresholds. These data provide a physiological basis for the nociceptive behaviors that arise following intraplantar injection of glutamate or glutamate agonists. Furthermore, demonstration of glutamate-induced excitation and heat sensitization of nociceptors indicates that local or topical administration of glutamate receptor antagonists may have therapeutic potential for the treatment of pain.

  • kainate induced excitation and sensitization of nociceptors in normal and inflamed rat Glabrous Skin
    Neuroscience, 2006
    Co-Authors: Junhui Du, Shengtai Zhou, Susan M Carlton
    Abstract:

    Abstract This study investigates contributions of peripheral kainate receptors to acute nociception and persistent inflammatory pain in rat. Immunohistochemical analysis of kainate receptor expression using antibodies recognizing glutamate receptor subunits 5, 6, and 7 demonstrates that 28% of unmyelinated axons in normal digital nerve are positively labeled. Following intraplantar injection of complete Freund’s adjuvant, a significant increase in glutamate receptor subunits 5, 6, and 7-labeled axons occurs at 2 days (40%), but not 7 (31%) or 14 days (28%) post-complete Freund’s adjuvant. In behavioral studies, we confirm an increased mechanical sensitivity in complete Freund’s adjuvant-injected hind paws. Furthermore, activation of kainate receptors following intraplantar injection of 1.0mM kainate in normal animals results in a mechanical sensitivity similar to that observed in inflamed animals. A 1.0mM kainate injection into inflamed hind paws further enhances the mechanical sensitivity. Injection of the non– N -methyl- d -aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (0.1mM) reverses complete Freund’s adjuvant-induced mechanical sensitivity through a local effect. In single unit recordings from nociceptors in a Glabrous Skin-nerve preparation, mechanical sensitization is present in inflamed Skin evidenced by a decrease in mechanical threshold and an increase in discharge rate during a suprathreshold, constant force stimulus. Thermal sensitization is also present evidenced by a decrease in heat threshold. There is a dose-dependent increase in kainate-induced nociceptor activity in both normal and inflamed Skin but the kainate required to induce activation is reduced in inflamed Skin. Although proportions of kainate-activated nociceptors are the same in normal and inflamed Skin, the kainate-induced mean discharge rate is significantly enhanced in inflamed Skin. Exposure of normal and inflamed nociceptors to 0.3mM kainate sensitizes fibers to re-application of kainate and heat. This sensitization is blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione or the glutamate receptor subunit 5 selective antagonist 3 S ,4a R ,6 S ,8a R -6-[4-carboxy-phenyl] methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid. The data indicate that peripheral kainate receptors not only play an important role in normal nociception but also contribute to mechanical sensitivity and heat sensitization accompanying inflammatory pain.

  • inflammation induced up regulation of neurokinin 1 receptors in rat Glabrous Skin
    Neuroscience Letters, 2002
    Co-Authors: Susan M Carlton, Richard E Coggeshall
    Abstract:

    Peripheral inflammation sensitizes primary afferent fibers causing lowered thresholds and increased responses to noxious input. One mechanism for sensitization might be increased expression of receptors whose activation results in nociceptor activity. Accordingly, the present study demonstrates that 15.6% of unmyelinated primary afferent axons in rat Glabrous Skin express the neurokinin 1 (NK1) receptor. At 48 h following hindpaw inflammation with complete Freund's adjuvant, the proportion of unmyelinated axons expressing NK1 receptors significantly increases to 23.6%. This implies a considerable upregulation of NK1 receptor synthesis in the dorsal root ganglia with subsequent transport to peripheral nociceptive terminals. Antagonizing peripheral NK1 receptors locally would be effective in reducing inflammatory pain by reducing neural transduction in NK1-expressing nociceptors as well as lessening the inflammatory vascular effects of peripheral substance P.

  • glutamate induced excitation and sensitization of nociceptors in rat Glabrous Skin
    Pain, 2001
    Co-Authors: Junhui Du, M Koltzenburg, Susan M Carlton
    Abstract:

    AbstractAnatomical studies demonstrate the presence of glutamate receptors on unmyelinated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the Glabrous Skin results in nociceptive behaviors. The present study descri

  • localization and activation of substance p receptors in unmyelinated axons of rat Glabrous Skin
    Brain Research, 1996
    Co-Authors: Susan M Carlton, Shengtai Zhou, Richard E Coggeshall
    Abstract:

    Abstract Immunohistochemical staining for the substance P (neurokinin 1, NK1) receptor labels 32% of the unmyelinated axons in the Glabrous Skin of the rat hindpaw. This is the first demonstration of substance P (SP) receptors associated with the membranes of primary afferent fibers. Injection of SP into the subcutaneous tissue of the third hind toe results in behavioral changes interpreted as mechanical hyperalgesia and mechanical allodynia. These nocifensive behaviors can be blocked by the NK1 antagonist CP99,994-1. The presence of peripheral axons immunolabelled for NK1 receptors and the demonstration that exogenous peripheral SP causes nocifensive behaviors would seem to indicate that SP can have a direct effect on sensory afferents with activation of these receptors resulting in fine afferent firing and thus the pain-related behaviors. Additionally, the presence of round, clear vesicles in some of the SP receptor-labelled axons suggests the presence of autoreceptors since it is known that many primary sensory afferents contain SP.