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William D. Willis - One of the best experts on this subject based on the ideXlab platform.

  • Intradermal Injection of capsaicin induces acute substance P release from rat spinal cord dorsal horn.
    Neuroscience Letters, 2006
    Co-Authors: Michael G. Hughes, David J. Mcadoo, William D. Willis
    Abstract:

    Increased release of substance P (SP) from the dorsal horn following noxious stimuli, such as spinal administration of capsaicin, has been demonstrated in previous studies. However, changes in the release of SP in response to Intradermal Injection of capsaicin still remain unknown. This study was designed to demonstrate in vivo spinal SP release following Intradermal Injection of capsaicin (3%, 50 μl), using polyimide tubing with a single hole introduced into the rat dorsal horn. The changes in the content of SP in the rat dorsal horn tissues before and after capsaicin (3%, 50 μl) Injection were also investigated. The SP concentration in the samples was analyzed using an enzyme-linked immunosorbent assay (ELISA). We found that Intradermal Injection of capsaicin induced a quick SP release within the dorsal horn. The peak of the release appeared around 10 min after the Injection. In contrast, Intradermal Injection of capsaicin had no significant effect on the SP content in the dorsal horn. This study has provided direct evidence of the effect of Intradermal Injection of capsaicin on SP release within the dorsal horn, with the major source being from the central terminals of primary afferents.

  • Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following Intradermal Injection of capsaicin
    Molecular Pain, 2006
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Background: Intradermal Injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by Intradermal Injection of capsaicin in rats. Results: In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle Injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin Injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following Intradermal Injection of capsaicin in rats. Capsaicin Injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the Injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion: These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by Intradermal Injection of capsaicin in rats, which may have implications in clinical pain therapy.

  • Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following Intradermal Injection of capsaicin.
    Molecular Brain Research, 2005
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Abstract The present study investigates the role of serine/threonine protein phosphatase 2A (PP2A) in the modulation of the phosphorylation of the NR1 and NR2B subunits of NMDA receptors in the spinal cord of rats following Intradermal Injection of capsaicin. The effects of a specific inhibitor of PP2A, fostriecin, on the expression of NR1, phospho-NR1, NR2B, and phospho-NR2B subunits of the NMDA receptor in the spinal cord of rats following noxious stimulation were examined. After continually perfusing with ACSF or fostriecin (3 μM) through a previously implanted microdialysis fiber for 30 min, central sensitization was initiated by Injection of capsaicin into the plantar surface of the left paw of rats. The spinal cord was removed at different time points (30, 60, 90, 120, 180 min) after Intradermal Injection of capsaicin. Western blots were performed to examine the expression of NMDA subunits in spinal cord tissue by using specific antibodies. We found that the upregulated phosphorylation of both NR1 and NR2B subunits induced by capsaicin Injection was significantly potentiated by the PP2A inhibitor without affecting the NR1 and NR2B protein itself. These results suggest that PP2A may have a regulatory effect on central sensitization induced by noxious stimuli in the periphery by regulating the phosphorylation state of NMDA receptors.

  • role of calcitonin gene related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after Intradermal Injection of capsaicin
    Journal of Neurophysiology, 2004
    Co-Authors: Nada B Lawand, William D. Willis
    Abstract:

    This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the sensitization of dorsal horn neurons induced by Intradermal Injection of capsaicin in ra...

  • the effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following Intradermal Injection of capsaicin
    Pain, 2003
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    The functions of crucial proteins in the nervous system are modulated by kinases and phosphatases which catalyze opposing reactions of phosphorylation and dephosphorylation. During spinal cord central sensitization, serine/threonine protein phosphatase 2A (PP2A) may play an important role in determining the excitability of nociceptive neurons in the spinal cord by modulating the phosphorylation state of some critical proteins. The effects of a general inhibitor of PP2A, okadaic acid (OA), and a specific inhibitor, fostriecin, on the behavioral responses of rats following capsaicin Injection were investigated in this study. Hyperalgesia was initiated by Injection of capsaicin into the plantar surface of the hindpaw of rats. An intrathecal catheter was previously implanted into the subarachnoid space of the spinal cord for the administration of a variety of drugs. Rats were tested for responses to mechanical stimuli using von Frey filaments of different bending forces applied at a site outside the area of Injection. Responses to heat stimuli were detected from a site near the Injection area. The responses were recorded before and after Injection of capsaicin with the perfusion of ACSF, OA negative control, OA or fostriecin at different time points. The results demonstrated that secondary mechanical hyperalgesia and allodynia can be induced by the Intradermal Injection of capsaicin. Compared to administration of ACSF or the OA negative control, infusion of the phosphatase inhibitor OA or of fostriecin into the subarachnoid space enhanced the secondary mechanical hyperalgesia and allodynia by making the Intradermal capsaicin-induced hyperalgesia and allodynia last longer.

Geoffrey L Smith - One of the best experts on this subject based on the ideXlab platform.

  • a model for vaccinia virus pathogenesis and immunity based on Intradermal Injection of mouse ear pinnae
    Journal of General Virology, 1999
    Co-Authors: David C Tscharke, Geoffrey L Smith
    Abstract:

    Vaccinia virus (VV) proteins that interfere with the host response to infection are of interest because they provide insight into virus–host relationships and may affect the safety and immunogenicity of recombinant VV (rVV) vaccines. Such vaccines need assessment in animal models and with this aim a model of VV infection based on Intradermal Injection of BALB/c ear pinnae was developed and characterized. In this model, the outcome of infection is affected by the dose of virus inoculated but virus spread is minimal and the mice suffer no signs of systemic illness. Cellular and humoral immune responses to these infections were measured readily and were independent of virus dose over a 100-fold range. Thus the model seems suitable for the analysis of the safety and immunogenicity of VV mutants lacking specific immunomodulatory proteins or bearing foreign antigens.

Li Fang - One of the best experts on this subject based on the ideXlab platform.

  • Roles of TRPV_1 and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by Intradermal Injection of capsaicin
    Molecular Pain, 2007
    Co-Authors: Dingge Li, Xijin Xu, Li Fang
    Abstract:

    Background Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV_1) receptors following Intradermal Injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV_1 receptors initiates neurogenic inflammation via triggering DRRs. Results Here we used pharmacological manipulations to analyze the roles of TRPV_1 and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by Intradermal Injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin Injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local Injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABA_A receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV_1 receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 μg. In contrast, pretreatment of the periphery with different doses of CGRP_8–37 (a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK_1 receptors were blocked by co-administration of CGRP_8–37 and spantide I, a stronger reduction in the capsaicin-initiated inflammation was produced. Conclusion Our data suggest that 1) the generation of DRRs is critical for driving the release of neuropeptides antidromically from primary afferent nociceptors; 2) activation of TRPV_1 receptors in primary afferent nociceptors following Intradermal capsaicin Injection initiates this process; 3) the released CGRP and SP participate in neurogenic inflammation.

  • roles of trpv1 and neuropeptidergic receptors in dorsal root reflex mediated neurogenic inflammation induced by Intradermal Injection of capsaicin
    Molecular Pain, 2007
    Co-Authors: Dingge Li, Xijin Xu, Li Fang
    Abstract:

    Background: Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV1) receptors following Intradermal Injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV 1 receptors initiates neurogenic inflammation via triggering DRRs. Results: Here we used pharmacological manipulations to analyze the roles of TRPV1 and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by Intradermal Injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin Injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local Injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABA A receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV1 receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 µg. In contrast, pretreatment of the periphery with different doses of CGRP 8–37 (a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK1 receptors were blocked by co-administration of CGRP8–37 and spantide I, a stronger reduction in the capsaicin-initiated inflammation was produced.

  • Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following Intradermal Injection of capsaicin
    Molecular Pain, 2006
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Background: Intradermal Injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by Intradermal Injection of capsaicin in rats. Results: In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle Injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin Injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following Intradermal Injection of capsaicin in rats. Capsaicin Injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the Injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion: These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by Intradermal Injection of capsaicin in rats, which may have implications in clinical pain therapy.

  • Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following Intradermal Injection of capsaicin.
    Molecular Brain Research, 2005
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Abstract The present study investigates the role of serine/threonine protein phosphatase 2A (PP2A) in the modulation of the phosphorylation of the NR1 and NR2B subunits of NMDA receptors in the spinal cord of rats following Intradermal Injection of capsaicin. The effects of a specific inhibitor of PP2A, fostriecin, on the expression of NR1, phospho-NR1, NR2B, and phospho-NR2B subunits of the NMDA receptor in the spinal cord of rats following noxious stimulation were examined. After continually perfusing with ACSF or fostriecin (3 μM) through a previously implanted microdialysis fiber for 30 min, central sensitization was initiated by Injection of capsaicin into the plantar surface of the left paw of rats. The spinal cord was removed at different time points (30, 60, 90, 120, 180 min) after Intradermal Injection of capsaicin. Western blots were performed to examine the expression of NMDA subunits in spinal cord tissue by using specific antibodies. We found that the upregulated phosphorylation of both NR1 and NR2B subunits induced by capsaicin Injection was significantly potentiated by the PP2A inhibitor without affecting the NR1 and NR2B protein itself. These results suggest that PP2A may have a regulatory effect on central sensitization induced by noxious stimuli in the periphery by regulating the phosphorylation state of NMDA receptors.

  • the effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following Intradermal Injection of capsaicin
    Pain, 2003
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    The functions of crucial proteins in the nervous system are modulated by kinases and phosphatases which catalyze opposing reactions of phosphorylation and dephosphorylation. During spinal cord central sensitization, serine/threonine protein phosphatase 2A (PP2A) may play an important role in determining the excitability of nociceptive neurons in the spinal cord by modulating the phosphorylation state of some critical proteins. The effects of a general inhibitor of PP2A, okadaic acid (OA), and a specific inhibitor, fostriecin, on the behavioral responses of rats following capsaicin Injection were investigated in this study. Hyperalgesia was initiated by Injection of capsaicin into the plantar surface of the hindpaw of rats. An intrathecal catheter was previously implanted into the subarachnoid space of the spinal cord for the administration of a variety of drugs. Rats were tested for responses to mechanical stimuli using von Frey filaments of different bending forces applied at a site outside the area of Injection. Responses to heat stimuli were detected from a site near the Injection area. The responses were recorded before and after Injection of capsaicin with the perfusion of ACSF, OA negative control, OA or fostriecin at different time points. The results demonstrated that secondary mechanical hyperalgesia and allodynia can be induced by the Intradermal Injection of capsaicin. Compared to administration of ACSF or the OA negative control, infusion of the phosphatase inhibitor OA or of fostriecin into the subarachnoid space enhanced the secondary mechanical hyperalgesia and allodynia by making the Intradermal capsaicin-induced hyperalgesia and allodynia last longer.

David C Tscharke - One of the best experts on this subject based on the ideXlab platform.

  • a model for vaccinia virus pathogenesis and immunity based on Intradermal Injection of mouse ear pinnae
    Journal of General Virology, 1999
    Co-Authors: David C Tscharke, Geoffrey L Smith
    Abstract:

    Vaccinia virus (VV) proteins that interfere with the host response to infection are of interest because they provide insight into virus–host relationships and may affect the safety and immunogenicity of recombinant VV (rVV) vaccines. Such vaccines need assessment in animal models and with this aim a model of VV infection based on Intradermal Injection of BALB/c ear pinnae was developed and characterized. In this model, the outcome of infection is affected by the dose of virus inoculated but virus spread is minimal and the mice suffer no signs of systemic illness. Cellular and humoral immune responses to these infections were measured readily and were independent of virus dose over a 100-fold range. Thus the model seems suitable for the analysis of the safety and immunogenicity of VV mutants lacking specific immunomodulatory proteins or bearing foreign antigens.

Jing Wu - One of the best experts on this subject based on the ideXlab platform.

  • Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following Intradermal Injection of capsaicin
    Molecular Pain, 2006
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Background: Intradermal Injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by Intradermal Injection of capsaicin in rats. Results: In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle Injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin Injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following Intradermal Injection of capsaicin in rats. Capsaicin Injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the Injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion: These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by Intradermal Injection of capsaicin in rats, which may have implications in clinical pain therapy.

  • Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following Intradermal Injection of capsaicin.
    Molecular Brain Research, 2005
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    Abstract The present study investigates the role of serine/threonine protein phosphatase 2A (PP2A) in the modulation of the phosphorylation of the NR1 and NR2B subunits of NMDA receptors in the spinal cord of rats following Intradermal Injection of capsaicin. The effects of a specific inhibitor of PP2A, fostriecin, on the expression of NR1, phospho-NR1, NR2B, and phospho-NR2B subunits of the NMDA receptor in the spinal cord of rats following noxious stimulation were examined. After continually perfusing with ACSF or fostriecin (3 μM) through a previously implanted microdialysis fiber for 30 min, central sensitization was initiated by Injection of capsaicin into the plantar surface of the left paw of rats. The spinal cord was removed at different time points (30, 60, 90, 120, 180 min) after Intradermal Injection of capsaicin. Western blots were performed to examine the expression of NMDA subunits in spinal cord tissue by using specific antibodies. We found that the upregulated phosphorylation of both NR1 and NR2B subunits induced by capsaicin Injection was significantly potentiated by the PP2A inhibitor without affecting the NR1 and NR2B protein itself. These results suggest that PP2A may have a regulatory effect on central sensitization induced by noxious stimuli in the periphery by regulating the phosphorylation state of NMDA receptors.

  • the effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following Intradermal Injection of capsaicin
    Pain, 2003
    Co-Authors: Xuan Zhang, Jing Wu, Li Fang, William D. Willis
    Abstract:

    The functions of crucial proteins in the nervous system are modulated by kinases and phosphatases which catalyze opposing reactions of phosphorylation and dephosphorylation. During spinal cord central sensitization, serine/threonine protein phosphatase 2A (PP2A) may play an important role in determining the excitability of nociceptive neurons in the spinal cord by modulating the phosphorylation state of some critical proteins. The effects of a general inhibitor of PP2A, okadaic acid (OA), and a specific inhibitor, fostriecin, on the behavioral responses of rats following capsaicin Injection were investigated in this study. Hyperalgesia was initiated by Injection of capsaicin into the plantar surface of the hindpaw of rats. An intrathecal catheter was previously implanted into the subarachnoid space of the spinal cord for the administration of a variety of drugs. Rats were tested for responses to mechanical stimuli using von Frey filaments of different bending forces applied at a site outside the area of Injection. Responses to heat stimuli were detected from a site near the Injection area. The responses were recorded before and after Injection of capsaicin with the perfusion of ACSF, OA negative control, OA or fostriecin at different time points. The results demonstrated that secondary mechanical hyperalgesia and allodynia can be induced by the Intradermal Injection of capsaicin. Compared to administration of ACSF or the OA negative control, infusion of the phosphatase inhibitor OA or of fostriecin into the subarachnoid space enhanced the secondary mechanical hyperalgesia and allodynia by making the Intradermal capsaicin-induced hyperalgesia and allodynia last longer.

  • dorsal root reflexes and cutaneous neurogenic inflammation after Intradermal Injection of capsaicin in rats
    Journal of Neurophysiology, 1999
    Co-Authors: Jing Wu, William D. Willis
    Abstract:

    The role of dorsal root reflexes (DRRs) in acute cutaneous neurogenic inflammation induced by Intradermal Injection of capsaicin (CAP) was examined in anesthetized rats. Changes in cutaneous blood ...