Cell type-specific calcium imaging of central sensitization in mouse dorsal horn

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 3, 2022

Abstract Allodynia is a state in which pain elicited by innocuous stimuli. Capsaicin applied to the skin results an allodynia that extends broad region beyond application site. This sensitization thought be mediated spinal networks; however, we do not have clear picture of neurons mediate this phenomenon. To address gap, used two-photon calcium imaging excitatory interneurons and projection mouse dorsal horn. distinguish among neuronal subtypes, developed CICADA, cell profiling approach identify types during imaging. We then identified capsaicin-responsive capsaicin-sensitized populations. Capsaicin-sensitized showed emergent responses input increased receptive field sizes consistent with psychophysical reports. Finally, output enhanced from input. These experiments provide population-level view central framework model somatosensory integration

Язык: Английский

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Glycine Receptors in Spinal Nociceptive Control—An Update

Biomolecules, Год журнала: 2021, Номер 11(6), С. 846 - 846

Опубликована: Июнь 6, 2021

Diminished inhibitory control of spinal nociception is one the major culprits chronic pain states. Restoring proper synaptic inhibition a well-established rational therapeutic approach explored by several pharmaceutical companies. A particular challenge arises from need for site-specific intervention to avoid deleterious side effects such as sedation, addiction, or impaired motor control, which would arise wide-range facilitation inhibition. Specific targeting glycinergic inhibition, dominates in cord and parts hindbrain, may help reduce these effects. Selective α3 subtype glycine receptors (GlyRs), highly enriched superficial layers dorsal horn, key site nociceptive processing, further narrow down pharmacological on system increase tolerability. This review provides an update physiological properties functions GlyRs present state related drug discovery programs.

Язык: Английский

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Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Pain, Год журнала: 2021, Номер 163(3), С. e432 - e452

Опубликована: Июль 28, 2021

Abstract Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily laminae II inner and III. Inhibitory PVINs play an important role segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors postsynaptic distinct circuits. By comparison, relatively little is known excitatory (ePVINs) sensory processing. Here, we use neuroanatomical optogenetic approaches to show that ePVINs comprise a larger proportion PVIN population than previously reported both ePVIN inhibitory populations form synaptic connections among (and between) themselves. We find these cells contribute neuronal networks influence activity within several functionally aberrant under pathological conditions well placed development mechanical hypersensitivity.

Язык: Английский

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Advances and Barriers in Understanding Presynaptic N-Methyl-D-Aspartate Receptors in Spinal Pain Processing

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Март 31, 2022

For decades, N -methyl- D -aspartate (NMDA) receptors have been known to play a critical role in the modulation of both acute and chronic pain. Of particular interest are NMDA expressed superficial dorsal horn (SDH) spinal cord, which houses nociceptive processing circuits cord. In SDH, undergo potentiation increases trafficking synapse, contribute excitability plastic output from SDH brain. Research efforts primarily focused on postsynaptic receptors, despite findings that presynaptic can similar changes their counterparts. Recent technological advances pivotal discovery mechanisms within SDH. Here, we highlight these recent understanding receptor physiology models We discuss specific subunits membranes afferents local interneurons, including across pain modalities. Furthermore, how barriers such as lack sex-inclusive research differences neurodevelopmental timepoints complicated investigations into roles pathological states. A more complete function states is needed shed light potential new therapeutic treatments for

Язык: Английский

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The Known Biology of Neuropathic Pain and Its Relevance to Pain Management

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Год журнала: 2023, Номер 51(1), С. 32 - 39

Опубликована: Фев. 17, 2023

ABSTRACT: Patients with neuropathic pain are heterogeneous in pathophysiology, etiology, and clinical presentation. Signs symptoms determined by the nature of injury factors such as genetics, sex, prior injury, age, culture, environment. Basic science has provided general information about etiology studying consequences peripheral rodent models. This is associated release inflammatory cytokines, chemokines, growth that sensitize sensory nerve endings, alter gene expression, promote post-translational modification proteins, ion channel function. leads to spontaneous activity primary afferent neurons crucial for onset persistence secondary mediators colony-stimulating factor 1 from terminals. These tertiary brain-derived neurotrophic interleukin-1β microglia astrocytes. Tertiary facilitate transmission nociceptive at spinal, thalamic, cortical levels. For most part, these findings have failed identify new therapeutic approaches. More recent basic better mirrored situation addressing pathophysiology specific types refinement methodology, attention various contributory sex. Improved quantification profiles each patient their distribution into defined clusters may improve translation between practice. If can be traced back cellular molecular aspects this lead personalized medicine approaches dictate a rational approach individual.

Язык: Английский

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