Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation

Abstract

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8–T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8–T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.

Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain

“…We found that glia outnumbered neurons (20 to 1) in this section of the cord. 12 These results imply that when an electrical field is applied to the dorsal aspect of the cord, it affects both neuron and glial cells and thus the ability to modulate the homeostatic milieu resulting from neuroglial interactions.…”

Modulation of microglial activation states by spinal cord stimulation in an animal model of neuropathic pain: Comparing high rate, low rate, and differential target multiplexed programming

“…Although neurons and glial cells are the main cellular constituents of neural tissue, glial cells are more abundant than neurons in the spinal cord of primates, including humans. 2 – 4 Among spinal glia, microglia and astrocytes are known to be integral to the establishment and maintenance of neuropathic pain. 5 – 7 Our group previously reported on the distinctive response of glia and neurons when exposed to different electrical signals, 8 , 9 demonstrating that electrical stimulation of the spinal cord may be used to differentially modulate those cells and provide improved relief of neuropathic pain in an animal model.…”

Current Perspectives on Neurostimulation for the Management of Chronic Low Back Pain: A Narrative Review

“… Further examination of optimal lead selection, lead position, and parameters of stimulation. Target region: T9–T10; non-neuronal cells in the nervous system Ruiz-Sauri 2019 72 Dissection of posterior spinal cord segments from 11 human cadavers. Glial to neuronal ratio in posterior gray matter within the T8– T11 vertebral region ranges from 11:1 to 13:1.…”

“… 71 Basic science research has indicated that glial cells outnumber neurons in the spinal cord 20:1, are electrically excitable, and have the ability to modulate ascending pain pathways. 72 , 73 This evidence allowed researchers to hypothesize that SCS parameters can be adjusted to differentially target neurons and glial cells in order to maximize the efficacy of treatment. 64 …”