Skip to main content

MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling.

Publication ,  Journal Article
Chen, O; Jiang, C; Berta, T; Powell Gray, B; Furutani, K; Sullenger, BA; Ji, R-R
Published in: Pain
March 6, 2024

Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. Patch-clamp recordings also demonstrated enhanced excitatory synaptic transmission (miniature excitatory postsynaptic currents [EPSCs]) in spinal nociceptive neurons following let-7b perfusion or optogenetic activation of axonal terminals. The elevation in spinal calcium signaling and EPSCs was dependent on the presence of toll-like receptor-7 (TLR7) and transient receptor potential ion channel subtype A1 (TRPA1). In addition, endogenous let-7b is enriched in spinal cord synaptosome, and peripheral inflammation increased let-7b in doral root ganglion/dorsal root ganglia neurons, spinal cord tissue, and the cerebrospinal fluid. Notably, let-7b antagomir inhibited inflammatory pain and inflammation-induced synaptic plasticity (EPSC increase), suggesting an endogenous role of let-7b in regulating pain and synaptic transmission. Furthermore, intrathecal injection of let-7b, at a higher dose (10 μg), induced persistent mechanical allodynia for >2 weeks, which was abolished in Tlr7-/- mice. The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

March 6, 2024

Location

United States

Related Subject Headings

  • Anesthesiology
  • 52 Psychology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 17 Psychology and Cognitive Sciences
  • 11 Medical and Health Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, O., Jiang, C., Berta, T., Powell Gray, B., Furutani, K., Sullenger, B. A., & Ji, R.-R. (2024). MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling. Pain. https://doi.org/10.1097/j.pain.0000000000003206
Chen, Ouyang, Changyu Jiang, Temugin Berta, Bethany Powell Gray, Kenta Furutani, Bruce A. Sullenger, and Ru-Rong Ji. “MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling.Pain, March 6, 2024. https://doi.org/10.1097/j.pain.0000000000003206.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

March 6, 2024

Location

United States

Related Subject Headings

  • Anesthesiology
  • 52 Psychology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 17 Psychology and Cognitive Sciences
  • 11 Medical and Health Sciences