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  1. Article ; Online: Paclitaxel in vitro reversibly sensitizes the excitability of IB4(-) and IB4(+) sensory neurons from male and female rats.

    Villalba-Riquelme, Eva / de la Torre-Martínez, Roberto / Fernández-Carvajal, Asia / Ferrer-Montiel, Antonio

    British journal of pharmacology

    2022  Volume 179, Issue 14, Page(s) 3693–3710

    Abstract: Background and purpose: Paclitaxel produces a chemotherapy-induced peripheral neuropathy that persists in 50-60% of cancer patients upon treatment. Evidence from animal models suggests an axonopathy of peripheral A- and C-type fibres that affects their ... ...

    Abstract Background and purpose: Paclitaxel produces a chemotherapy-induced peripheral neuropathy that persists in 50-60% of cancer patients upon treatment. Evidence from animal models suggests an axonopathy of peripheral A- and C-type fibres that affects their excitability. However, direct effects of paclitaxel on sensory neuron excitability and sexual dimorphism remain poorly understood.
    Experimental approach: We used a long-lasting (10 days in vitro) primary culture of rat dorsal root ganglion (DRG) neurons to investigate the time course effect of paclitaxel on the electrical activity of IB4(-) and IB4(+) sensory neurons of female and male adult Wistar rats.
    Key results: Paclitaxel strongly and reversibly stimulated spontaneous activity and augmented action potential tonic firing in IB4(-) and IB4(+) neurons in both sexes, peaking at 48 h post-treatment and virtually disappearing at 96 h. Paclitaxel decreased the current rheobase for action potential firing by reducing and accelerating the after-hyperpolarization phase. Molecularly, paclitaxel modulated Na
    Conclusions and implications: Our data indicate that paclitaxel similarly potentiated IB4(-) and IB4(+) electrogenicity and uncover a potential sex dimorphism in paclitaxel-induced chemotherapy-induced peripheral neuropathy. Our in vitro, pre-clinical, chemotherapy-induced peripheral neuropathy paradigm provides a tool for studying the dynamics and underlying molecular mechanisms contributing to nociceptor sensitization in peripheral neuropathies and for testing desensitizing compounds.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Female ; Ganglia, Spinal ; Humans ; Male ; Paclitaxel/pharmacology ; Peripheral Nervous System Diseases ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sensory Receptor Cells
    Chemical Substances Antineoplastic Agents ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2022-03-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uf I Zs.146: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention.

    Cabañero, David / Villalba-Riquelme, Eva / Fernández-Ballester, Gregorio / Fernández-Carvajal, Asia / Ferrer-Montiel, Antonio

    Pharmacology & therapeutics

    2022  Volume 240, Page(s) 108297

    Abstract: Chronic pain is a major burden for the society and remains more prevalent and severe in females. The presence of chronic pain is linked to persistent alterations in the peripheral and the central nervous system. One of the main types of peripheral pain ... ...

    Abstract Chronic pain is a major burden for the society and remains more prevalent and severe in females. The presence of chronic pain is linked to persistent alterations in the peripheral and the central nervous system. One of the main types of peripheral pain transducers are the transient receptor potential channels (TRP), also known as thermoTRP channels, which intervene in the perception of hot and cold external stimuli. These channels, and especially TRPV1, TRPA1 and TRPM8, have been subjected to profound investigation because of their role as thermosensors and also because of their implication in acute and chronic pain. Surprisingly, their sensitivity to endogenous signaling has been far less studied. Cumulative evidence suggests that the function of these channels may be differently modulated in males and females, in part through sexual hormones, and this could constitute a significant contributor to the sex differences in chronic pain. Here, we review the exciting advances in thermoTRP pharmacology for males and females in two paradigmatic types of chronic pain with a strong peripheral component: chronic migraine and chemotherapy-induced peripheral neuropathy (CIPN). The possibilities of peripheral druggability offered by these channels and the differential exploitation for men and women represent a development opportunity that will lead to a significant increment of the armamentarium of analgesic medicines for personalized chronic pain treatment.
    MeSH term(s) Female ; Humans ; Male ; Analgesics/therapeutic use ; Chronic Pain/drug therapy ; Migraine Disorders/drug therapy ; Sex Characteristics ; Transient Receptor Potential Channels/metabolism ; Peripheral Nervous System Diseases ; Antineoplastic Agents/adverse effects ; Thermoreceptors/metabolism
    Chemical Substances Analgesics ; Transient Receptor Potential Channels ; Antineoplastic Agents
    Language English
    Publishing date 2022-10-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2022.108297
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1183: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  3. Article ; Online: Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI.

    Hingorani, Sonia / Paniagua Soriano, Guillem / Sánchez Huertas, Carlos / Villalba Riquelme, Eva María / López Mocholi, Eric / Martínez Rojas, Beatriz / Alastrué Agudo, Ana / Dupraz, Sebastián / Ferrer Montiel, Antonio Vicente / Moreno Manzano, Victoria

    Molecular therapy : the journal of the American Society of Gene Therapy

    2024  

    Abstract: Spinal cord injury (SCI) is a debilitating condition currently lacking treatment. Severe SCI causes the loss of most supraspinal inputs and neuronal activity caudal to the injury, which, coupled with the limited endogenous capacity for spontaneous ... ...

    Abstract Spinal cord injury (SCI) is a debilitating condition currently lacking treatment. Severe SCI causes the loss of most supraspinal inputs and neuronal activity caudal to the injury, which, coupled with the limited endogenous capacity for spontaneous regeneration, can lead to complete functional loss even in anatomically incomplete lesions. We hypothesized that transplantation of mature dorsal root ganglia (DRGs) genetically modified to express the NaChBac sodium channel could serve as a therapeutic option for functionally complete SCI. We found that NaChBac expression increased the intrinsic excitability of DRG neurons and promoted cell survival and neurotrophic factor secretion in vitro. Transplantation of NaChBac-expressing dissociated DRGs improved voluntary locomotion 7 weeks after injury compared to control groups. Animals transplanted with NaChBac-expressing DRGs also possessed higher tubulin-positive neuronal fiber and myelin preservation, although serotonergic descending fibers remained unaffected. We observed early preservation of the corticospinal tract 14 days after injury and transplantation, which was lost 7 weeks after injury. Nevertheless, transplantation of NaChBac-expressing DRGs increased the neuronal excitatory input by an increased number of VGLUT2 contacts immediately caudal to the injury. Our work suggests that the transplantation of NaChBac-expressing dissociated DRGs can rescue significant motor function, retaining an excitatory neuronal relay activity immediately caudal to injury.
    Language English
    Publishing date 2024-03-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2024.03.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
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