Age-dependent decrease in inhibitory drive on the excitatory superficial spinal dorsal horn neurons

Prudhvi Raj Rayi, Shaya Lev, Alexander M. Binshtok

Research output: Contribution to journalArticlepeer-review

Abstract

The excitatory and inhibitory interneurons of superficial laminae I-II of the spinal dorsal horn (SDH) receive and process pain-related information from the primary afferents and transmit it to the brain via the projection neurons. Thus, the interaction between excitatory and inhibitory SDH interneurons is crucial in determining the output from the spinal cord network. Disruption of this interaction in pathological conditions leads to increased SDH output to the higher brain centers, which could underlie pathological pain. Here, we examined whether the changes in the intrinsic SDH connectivity also occur with age, possibly underlying age-related increase in pain sensitivity. Using Vgat;tdTomato transgenic mouse line, we compared the spontaneous inhibitory postsynaptic currents (sIPSCs) in inhibitory tdTomato+ and excitatory tdTomato interneurons between adult (3–5 m.o.) and aged (12–13 m.o.) mice. We demonstrate that in adult mice, the amplitude and frequency of the sIPSCs on the excitatory interneurons were significantly higher than on inhibitory interneurons. These differences were annulled in aged mice. Further, we show that in aged mice, excitatory neurons receive less inhibition than in adult mice. This could lead to overall disinhibition of the SDH network, which might underlie increased pain perception among the aged population.

Original languageAmerican English
Article number100139
JournalNeurobiology of Pain
Volume14
DOIs
StatePublished - 1 Aug 2023

Keywords

  • Aging
  • Inhibition
  • Inhibitory synaptic transmission
  • Pain
  • Superficial spinal dorsal horn
  • Whole-cell patch clamp

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neuroscience (miscellaneous)

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