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  1. Article ; Online: Non-pharmacological Treatment of Pain: Grand Challenge and Future Opportunities.

    Bushnell, Mary Catherine / Frangos, Eleni / Madian, Nicholas

    Frontiers in pain research (Lausanne, Switzerland)

    2021  Volume 2, Page(s) 696783

    Language English
    Publishing date 2021-05-28
    Publishing country Switzerland
    Document type Editorial
    ISSN 2673-561X
    ISSN (online) 2673-561X
    DOI 10.3389/fpain.2021.696783
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Aβ-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers.

    Case, Laura K / Madian, Nicholas / McCall, Micaela V / Bradson, Megan L / Liljencrantz, Jaquette / Goldstein, Benjamin / Alasha, Vincent J / Zimmerman, Marisa S

    eNeuro

    2023  Volume 10, Issue 5

    Abstract: Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. ... ...

    Abstract Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinothalamic pathway- thought to convey all C-fiber sensations- in patients with cancer pain impaired pain, temperature, and itch, but not ratings of pleasant touch. This suggested integration of afferent A and CT fiber input in the spinal cord, or mechanoreceptive A-fiber contributions to computations of touch pleasantness in the brain. However, contribution of mechanoreceptive A-fibers to touch pleasantness, in humans without pain, remains unknown. In the current, single-blinded study, we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when mechanoreceptive A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gentle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on afferent A-fibers.
    MeSH term(s) Adult ; Humans ; Touch/physiology ; Mechanoreceptors ; Physical Stimulation ; Touch Perception/physiology ; Pain ; Tomography, X-Ray Computed
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0504-22.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

    Case, Laura K / Liljencrantz, Jaquette / Madian, Nicholas / Necaise, Aaron / Tubbs, Justin / McCall, Micaela / Bradson, Megan L / Szczot, Marcin / Pitcher, Mark H / Ghitani, Nima / Frangos, Eleni / Cole, Jonathan / Bharucha-Goebel, Diana / Saade, Dimah / Ogata, Tracy / Donkervoort, Sandra / Foley, A Reghan / Bönnemann, Carsten G / Olausson, Håkan /
    Bushnell, M Catherine / Chesler, Alexander T

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 657

    Abstract: The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative ... ...

    Abstract The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aβ fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aβ afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.
    MeSH term(s) Adult ; Aged ; Female ; Humans ; Ion Channels/genetics ; Ion Channels/physiology ; Male ; Mechanoreceptors/metabolism ; Mechanoreceptors/physiology ; Middle Aged ; Mutation ; Nerve Block/methods ; Pressure ; Proprioception/genetics ; Proprioception/physiology ; Sensation/physiology ; Sensation Disorders/diagnosis ; Sensation Disorders/genetics ; Sensation Disorders/physiopathology ; Skin/innervation ; Skin/physiopathology ; Touch/physiology ; Young Adult
    Chemical Substances Ion Channels ; PIEZO2 protein, human
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-20939-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.

    Walitt, Brian / Singh, Komudi / LaMunion, Samuel R / Hallett, Mark / Jacobson, Steve / Chen, Kong / Enose-Akahata, Yoshimi / Apps, Richard / Barb, Jennifer J / Bedard, Patrick / Brychta, Robert J / Buckley, Ashura Williams / Burbelo, Peter D / Calco, Brice / Cathay, Brianna / Chen, Li / Chigurupati, Snigdha / Chen, Jinguo / Cheung, Foo /
    Chin, Lisa M K / Coleman, Benjamin W / Courville, Amber B / Deming, Madeleine S / Drinkard, Bart / Feng, Li Rebekah / Ferrucci, Luigi / Gabel, Scott A / Gavin, Angelique / Goldstein, David S / Hassanzadeh, Shahin / Horan, Sean C / Horovitz, Silvina G / Johnson, Kory R / Govan, Anita Jones / Knutson, Kristine M / Kreskow, Joy D / Levin, Mark / Lyons, Jonathan J / Madian, Nicholas / Malik, Nasir / Mammen, Andrew L / McCulloch, John A / McGurrin, Patrick M / Milner, Joshua D / Moaddel, Ruin / Mueller, Geoffrey A / Mukherjee, Amrita / Muñoz-Braceras, Sandra / Norato, Gina / Pak, Katherine / Pinal-Fernandez, Iago / Popa, Traian / Reoma, Lauren B / Sack, Michael N / Safavi, Farinaz / Saligan, Leorey N / Sellers, Brian A / Sinclair, Stephen / Smith, Bryan / Snow, Joseph / Solin, Stacey / Stussman, Barbara J / Trinchieri, Giorgio / Turner, Sara A / Vetter, C Stephenie / Vial, Felipe / Vizioli, Carlotta / Williams, Ashley / Yang, Shanna B / Nath, Avindra

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 907

    Abstract: Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous ... ...

    Abstract Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
    MeSH term(s) Humans ; Fatigue Syndrome, Chronic/metabolism ; Leukocytes, Mononuclear/metabolism ; Communicable Diseases/metabolism ; Biomarkers/metabolism ; Phenotype
    Chemical Substances Biomarkers
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45107-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin

    Haspel Gal / Madian Nicholas / Navarro Julia / Scholl Lindsey / Lopez Matthew / Keller Jason M / Bates Brian D / Mitchell Kendall / Nemenov Michael I / Iadarola Michael J

    Molecular Pain, Vol 6, Iss 1, p

    analysis of withdrawal behaviors, recovery of function and molecular correlates

    2010  Volume 94

    Abstract: Abstract Background Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads ... ...

    Abstract Abstract Background Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy. Results RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal. Conclusion Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.
    Keywords Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 150
    Language English
    Publishing date 2010-12-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates.

    Mitchell, Kendall / Bates, Brian D / Keller, Jason M / Lopez, Matthew / Scholl, Lindsey / Navarro, Julia / Madian, Nicholas / Haspel, Gal / Nemenov, Michael I / Iadarola, Michael J

    Molecular pain

    2010  Volume 6, Page(s) 94

    Abstract: Background: Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to ... ...

    Abstract Background: Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy.
    Results: RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal.
    Conclusion: Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.
    MeSH term(s) Ablation Techniques ; Animals ; Behavior, Animal/drug effects ; Diterpenes/administration & dosage ; Diterpenes/pharmacology ; Electric Stimulation ; Foot ; Hot Temperature ; Lasers ; Male ; Nerve Fibers, Myelinated/drug effects ; Nerve Fibers, Unmyelinated/drug effects ; Nerve Regeneration ; Neurotoxins ; Pain/drug therapy ; Pain/prevention & control ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/antagonists & inhibitors
    Chemical Substances Diterpenes ; Neurotoxins ; TRPV Cation Channels ; Trpv1 protein, rat ; resiniferatoxin (A5O6P1UL4I)
    Language English
    Publishing date 2010-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2174252-2
    ISSN 1744-8069 ; 1744-8069
    ISSN (online) 1744-8069
    ISSN 1744-8069
    DOI 10.1186/1744-8069-6-94
    Database MEDical Literature Analysis and Retrieval System OnLINE

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