Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain
Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in...
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Gespeichert in:
| Autor*in: |
Burton, M. [verfasserIn] |
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| Format: |
E-Artikel |
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| Erschienen: |
2019transfer abstract |
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| Übergeordnetes Werk: |
Enthalten in: Reliable redundancy resolution strategies for kinematically redundant parallel manipulators - Vieira, Hiparco Lins ELSEVIER, 2021, official journal of the American Pain Society, New York, NY |
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| Übergeordnetes Werk: |
volume:20 ; year:2019 ; number:4 ; pages:1 |
| Links: |
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| DOI / URN: |
10.1016/j.jpain.2019.01.016 |
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ELV046181180 |
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| 520 | |a Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. | ||
| 520 | |a Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. | ||
| 700 | 1 | |a Szabo-Pardi, T. |4 oth | |
| 700 | 1 | |a Garner, K. |4 oth | |
| 700 | 1 | |a Tierney, J. |4 oth | |
| 700 | 1 | |a Price, T. |4 oth | |
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10.1016/j.jpain.2019.01.016 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000999.pica (DE-627)ELV046181180 (ELSEVIER)S1526-5900(19)30093-8 DE-627 ger DE-627 rakwb 620 VZ 52.20 bkl 50.32 bkl 50.25 bkl Burton, M. verfasserin aut Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Szabo-Pardi, T. oth Garner, K. oth Tierney, J. oth Price, T. oth Enthalten in Elsevier Vieira, Hiparco Lins ELSEVIER Reliable redundancy resolution strategies for kinematically redundant parallel manipulators 2021 official journal of the American Pain Society New York, NY (DE-627)ELV006838596 volume:20 year:2019 number:4 pages:1 https://doi.org/10.1016/j.jpain.2019.01.016 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 52.20 Antriebstechnik Getriebelehre VZ 50.32 Dynamik Schwingungslehre Technische Mechanik VZ 50.25 Robotertechnik VZ AR 20 2019 4 1 20.2019, 4, S1- |
| spelling |
10.1016/j.jpain.2019.01.016 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000999.pica (DE-627)ELV046181180 (ELSEVIER)S1526-5900(19)30093-8 DE-627 ger DE-627 rakwb 620 VZ 52.20 bkl 50.32 bkl 50.25 bkl Burton, M. verfasserin aut Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Szabo-Pardi, T. oth Garner, K. oth Tierney, J. oth Price, T. oth Enthalten in Elsevier Vieira, Hiparco Lins ELSEVIER Reliable redundancy resolution strategies for kinematically redundant parallel manipulators 2021 official journal of the American Pain Society New York, NY (DE-627)ELV006838596 volume:20 year:2019 number:4 pages:1 https://doi.org/10.1016/j.jpain.2019.01.016 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 52.20 Antriebstechnik Getriebelehre VZ 50.32 Dynamik Schwingungslehre Technische Mechanik VZ 50.25 Robotertechnik VZ AR 20 2019 4 1 20.2019, 4, S1- |
| allfields_unstemmed |
10.1016/j.jpain.2019.01.016 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000999.pica (DE-627)ELV046181180 (ELSEVIER)S1526-5900(19)30093-8 DE-627 ger DE-627 rakwb 620 VZ 52.20 bkl 50.32 bkl 50.25 bkl Burton, M. verfasserin aut Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Szabo-Pardi, T. oth Garner, K. oth Tierney, J. oth Price, T. oth Enthalten in Elsevier Vieira, Hiparco Lins ELSEVIER Reliable redundancy resolution strategies for kinematically redundant parallel manipulators 2021 official journal of the American Pain Society New York, NY (DE-627)ELV006838596 volume:20 year:2019 number:4 pages:1 https://doi.org/10.1016/j.jpain.2019.01.016 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 52.20 Antriebstechnik Getriebelehre VZ 50.32 Dynamik Schwingungslehre Technische Mechanik VZ 50.25 Robotertechnik VZ AR 20 2019 4 1 20.2019, 4, S1- |
| allfieldsGer |
10.1016/j.jpain.2019.01.016 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000999.pica (DE-627)ELV046181180 (ELSEVIER)S1526-5900(19)30093-8 DE-627 ger DE-627 rakwb 620 VZ 52.20 bkl 50.32 bkl 50.25 bkl Burton, M. verfasserin aut Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Szabo-Pardi, T. oth Garner, K. oth Tierney, J. oth Price, T. oth Enthalten in Elsevier Vieira, Hiparco Lins ELSEVIER Reliable redundancy resolution strategies for kinematically redundant parallel manipulators 2021 official journal of the American Pain Society New York, NY (DE-627)ELV006838596 volume:20 year:2019 number:4 pages:1 https://doi.org/10.1016/j.jpain.2019.01.016 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U 52.20 Antriebstechnik Getriebelehre VZ 50.32 Dynamik Schwingungslehre Technische Mechanik VZ 50.25 Robotertechnik VZ AR 20 2019 4 1 20.2019, 4, S1- |
| allfieldsSound |
10.1016/j.jpain.2019.01.016 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000999.pica (DE-627)ELV046181180 (ELSEVIER)S1526-5900(19)30093-8 DE-627 ger DE-627 rakwb 620 VZ 52.20 bkl 50.32 bkl 50.25 bkl Burton, M. verfasserin aut Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain 2019transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. 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Uncovering Cell-Specific Mechanisms in Sex Differences in TLR4-Dependent Pain |
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Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. |
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Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. |
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Uncovering how different cell types recognize and respond to danger-associated molecular patterns (DAMPs) could lead to new therapeutic insights and a better understanding of basic mechanisms of pain plasticity. Recent studies have bought to light the necessity to discern sex-specific differences in various pain modalities and different cell-types that mediate these differences. These studies begin to uncover the role of neuroimmune interactions to mediate pain states in a sex-specific fashion. However, direct nociceptor activity and intrinsic properties in the context of immune action have not been at the forefront. DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences. |
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DAMPs are produced in a broad variety of tissue injury paradigms and are linked to the generation of pain and pain plasticity underlying chronic pain. High-mobility group-box 1 (HMGB1) is a major DAMP that regulates pain states, it is produced after injury, and activates toll-like receptor-4 (TLR4). Here we have employed a transgenic model that allows for cre-mediated reactivation of a floxed-null TLR4 allele, utilizing NaV1.8 and LysozymeM to drive cre expression in peripheral nociceptors or macrophages, respectively. We observed a robust sexual dimorphic behavioral effect in mechanical hypersensitivity and hyperalgesic priming when TLR4 is reactivated in peripheral macrophages in males versus nociceptors in females. After intraplantar administration of HMGB1, wild-type (WT) littermates of both sexes show a mechanical hypersensitivity that is recapitulated in males when TLR4 is only in macrophages and in females when TLR4 is active only in nociceptors. Conversely, macrophage TLR4 reactivated females and nociceptor TLR4 reactivated males did not develop mechanical hypersensitivity. Moreover, these cell-specific reactivated animals were also associated with increased hyperalgesic priming precipitated by prostaglandin E2 injection in respective groups (macrophages in males and nociceptors in females). Collectively our work demonstrates a cell-specific effect of TLR4 in acute pain plasticity and in the transition to a chronic pain state, pointing to clear sex differences.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Szabo-Pardi, T.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Garner, K.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tierney, J.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Price, T.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Vieira, Hiparco Lins ELSEVIER</subfield><subfield code="t">Reliable redundancy resolution strategies for kinematically redundant parallel manipulators</subfield><subfield code="d">2021</subfield><subfield code="d">official journal of the American Pain Society</subfield><subfield code="g">New York, NY</subfield><subfield code="w">(DE-627)ELV006838596</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:20</subfield><subfield code="g">year:2019</subfield><subfield code="g">number:4</subfield><subfield code="g">pages:1</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.jpain.2019.01.016</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">52.20</subfield><subfield code="j">Antriebstechnik</subfield><subfield code="j">Getriebelehre</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.32</subfield><subfield code="j">Dynamik</subfield><subfield code="j">Schwingungslehre</subfield><subfield code="x">Technische Mechanik</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.25</subfield><subfield code="j">Robotertechnik</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">20</subfield><subfield code="j">2019</subfield><subfield code="e">4</subfield><subfield code="h">1</subfield><subfield code="y">20.2019, 4, S1-</subfield></datafield></record></collection>
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