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.

Keywords: anatomy; glial cells; neurons; spinal cord.

Figure 1

Representative images: (A) neuronal bodies immunostained with anti‐NSE in the posterior aspect of the dorsal horn (20×); (B) morphometric view of (A); (C) astrocytes in gray matter immunostained with anti‐GFAP in the posterior aspect of the dorsal horn (20×); (D) morphometric view of (C); (E) oligodendrocytes in gray matter immunostained with anti‐Olig2 in the posterior aspect of the dorsal horn (20×); (F) morphometric view of (E); (G) microglia in gray matter immunostained with anti‐Cd11b/c in the posterior aspect of the dorsal horn (20×); (H) morphometric view of (G).

Figure 2

A box‐and‐whisker graph illustrating mean (diamonds), median counts, range and quartiles for neuronal bodies within the gray matter of the selected area of the dorsal horn in a given spinal cord segment.

Figure 3

Box‐and‐whisker graphs illustrating mean counts (diamonds), median counts, range and quartiles for glial cells within the gray and white matter for a given selected area within a spinal cord segment.

Figure 4

Bar graphs illustrating mean percentages of glial cell populations (astrocytes, oligodendrocytes and microglia) in gray (left) and white (right) matter of T8–T11 segments.

Figure 5

Percentage of glia cell types obtained by combining white and gray matter counts in the posterior aspect of the dorsal horn.