Sensory root demyelination: Transforming touch into pain

Ding, You-Quan; Qi, Jian-Guo

doi:10.1002/glia.24097

Cited by 4 publications

(2 citation statements)

References 153 publications

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Section: Discussionmentioning

confidence: 99%

“…Aberrant myelination has been implicated in various neuropathic conditions, and several studies show that demyelination is both sufficient and necessary to transform touch into pain. 27,38 Therefore, promoting myelin repair may reduce sensory hypersensitivity after peripheral nerve injury. 32,89 Recent clinical evidence suggests that improved regeneration correlates with a functional recovery after release of a compressed nerve, 8 thus targeting neurotrophic factors to enhance axon regeneration may have therapeutic benefit.…”

Section: Therapeutic Targeting Of Partial Crush Injury-induced Neurop...mentioning

confidence: 99%

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Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons

Kim

Shim

Zhao

et al. 2023

PAIN

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Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of “painful” nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete (“full”) or incomplete (“partial”) axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.

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Section: Discussionmentioning

confidence: 99%

Section: Therapeutic Targeting Of Partial Crush Injury-induced Neurop...mentioning

confidence: 99%

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons

Kim

Shim

Zhao

et al. 2023

PAIN

View full text Add to dashboard Cite

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Long-lasting pain and somatosensory disturbances in children with myelin oligodendrocyte glycoprotein antibody-associated disease

et al. 2023

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Selective RNAi-silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury

Itson-Zoske,

Gani,

Mikesell

et al. 2023

Preprint

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We previously reported functional Piezo1 expression in Schwann cells of the peripheral nervous system. This study is designed to further investigate the role of Schwann cell Piezo1 in peripheral nociception. We first developed an adeno-associated viral (AAV) vector that has primary Schwann cell tropism after delivery into the sciatic nerve. This was achieved by packing AAV-GFP transcribed by a hybrid CMV enhancer/chicken β-actin (CBA) promoter using a capsid AAVolig001 to generate AAVolig001-CBA-GFP. Five weeks after intrasciatic injection of AAVolig001-CBA-GFP in naïve rats, GFP expression was detected selectively in the Schwann cells of the sciatic nerve. A short hairpin RNA against rat Piezo1 (PZ1shRNA) was designed that showed efficient physical and functional knockdown of Piezo1 in NG108 neuronal cells. A dual promoter and bidirectional AAV encoding a U6-driven PZ1shRNA and CBA-transcribed GFP was packed with capsid olig001 (AAVolig001-PZ1shRNA), and AAV was injected into unilateral sciatic nerve immediately after induction of common peroneal nerve injury (CPNI). Results showed that the development of mechanical hypersensitivity in the CPNI rats injected with AAVolig001-PZ1shRNA was mitigated, compared to rats subjected with AAVolig001-scramble. Selective in vivo Schwann cell transduction and functional block of Piezo1 channel activity of primary cultured Schwann cells was confirmed. Together, our data demonstrate that 1) AAVolig001 has unique and selective primary tropism to Schwann cells via intrasciatic delivery and 2) Schwann cell Piezo1 contributes to mechanical hypersensitivity following nerve injury.

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Sensory root demyelination: Transforming touch into pain

Cited by 4 publications

References 153 publications

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons

Long-lasting pain and somatosensory disturbances in children with myelin oligodendrocyte glycoprotein antibody-associated disease

Selective RNAi-silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury

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