Signaling Pathways in Sensitization: Toward a Nociceptor Cell Biology

  title={Signaling Pathways in Sensitization: Toward a Nociceptor Cell Biology},
  author={Tim Hucho and Jon D. Levine},

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Information is provided on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.
Nociception and hypersensitivity involve distinct neurons and molecular transducers in Drosophila
In Drosophila larvae, heat sensing in the nociception and hypersensitivity states is mediated by distinct heat-sensitive neurons and TrpA1 alternative isoforms, providing a precedent that in vertebrate and invertebrate species, conserved transient receptor potential (Trp) channels are the primary transducers of noxious stimuli.
Intracellular Signaling in Primary Sensory Neurons and Persistent Pain
The evidence demonstrating that activation of multiple intracellular signal pathways such as MAPK pathways in primary sensory neurons results in the induction and maintenance of peripheral sensitization and produces persistent pain is reviewed.
Protein kinase A regulates inflammatory pain sensitization by modulating HCN2 channel activity in nociceptive sensory neurons
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Ca++/CaMKII switches nociceptor‐sensitizing stimuli into desensitizing stimuli
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An overview of pathways encoding nociception.
The underlying biological components of both physiological pain processing and pathological pain processing are described, as well as the acute to chronic pain transition and the role of innate and adaptive immunity in this transition.
Heterogeneity in primary nociceptive neurons: From molecules to pathology
An extraordinary diversity among nociceptors likely reflects the evolutionary adaptation required to respond to an extremely variety of circumstances.


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Inhibition of ERK phosphorylation by a MEK inhibitor reduced the second phase of formalin-induced pain behavior, a measure of spinal neuron sensitization, and ERK signaling within the spinal cord is therefore involved in generating pain hypersensitivity.
A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin.
  • P. Cesare, P. McNaughton
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
It is reported here that application of pulses of noxious heat to a subpopulation of isolated primary sensory neurons rapidly activates an inward current, and it is concluded that bradykinin sensitizes the response to heat by activating protein kinase C.
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It is concluded that a Ras–MEK–ERK1/2 cascade acts independent of PKA or PKCε as a novel signaling pathway for the production of inflammatory pain and may present a target for a new class of analgesic agents.
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Estrogen controls PKCepsilon-dependent mechanical hyperalgesia through direct action on nociceptive neurons
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Phosphorylation of Extracellular Signal-Regulated Kinase in Primary Afferent Neurons by Noxious Stimuli and Its Involvement in Peripheral Sensitization
PERK inPrimary afferents by noxious stimulationin vivo showed distinct characteristics of expression and may be correlated with the functional activity of primary afferent neurons.
A Novel Nociceptor Signaling Pathway Revealed in Protein Kinase C ε Mutant Mice
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Data is reviewed on the wealth of different mechanosensitive sensory neurons that innervate the authors' main somatic sense organ the skin and the cellular and molecular mechanisms by which mechanoreceptive sensory neurons signal both innocuous and noxious sensation are evaluated in the context of pain.