Altered functional properties of satellite glial cells in compressed spinal ganglia

Abstract

The cell bodies of sensory neurons in the dorsal root ganglion (DRG) are enveloped by satellite glial cells (SGCs). In an animal model of intervertebral foraminal stenosis and low-back pain, a chronic compression of the DRG (CCD) increases the excitability of neuronal cell bodies in the compressed ganglion. The morphological and electrophysiological properties of SGCs were investigated in both CCD and uninjured, control lumbar DRGs. SGCs responded within 12 hours of the onset of CCD as indicated by an increased expression of glial fibrillary acidic protein (GFAP) in the compressed DRG but to lesser extent in neighboring or contralateral DRGs. Within one week, coupling through gap junctions between SGCs was significantly enhanced in the compressed ganglion. Under whole-cell patch clamp recordings, inward and outward potassium currents, but not sodium currents, were detected in individual SGCs. SGCs enveloping differently sized neurons had similar electrophysiological properties. SGCs in the compressed vs. control DRG exhibited significantly reduced inwardly rectifying potassium currents (Kir), increased input resistances and positively shifted resting membrane potentials. The reduction in Kir was greater for nociceptive medium-sized neurons compared to non-nociceptive neurons. Kir currents of SGCs around spontaneously active neurons were significantly reduced one day after compression but recovered by 7 days. These data demonstrate rapid alterations in glial membrane currents and GFAP expression in close temporal association with the development of neuronal hyperexcitability in the CCD model of europathic pain. However, these alterations are not fully sustained and suggest other mechanisms for the maintenance of the hyperexcitable state.

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

“…Kir4.1 is confined to SGCs of sensory ganglia, where it is proposed to control K ϩ concentrations in the perineuronal environment and thereby regulate neuronal excitability (13)(14)(15)(16)(17). In intact DRG, we found that Kir4.1-immunoreactive (IR) SGCs completely ensheathed NeuN-IR neurons ( Fig.…”

“…SGCs also express Kir4.1 and display a high K ϩ conductance that is hypothesized to control [K ϩ ] of the perineuronal environment and regulate neuronal excitability. Reduction in Kir4.1 expression and mediated currents has been demonstrated during inflammation, and Kir4.1 silencing in sensory peripheral ganglia enhances pain (13)(14)(15)(16)(17). In inflammatory pain and disease states, SGCs can release ATP and cytokines that may increase neuronal excitability (18 -21).…”

Fractalkine mediates inflammatory pain through activation of satellite glial cells

“…Several studies correlate glial activation with an increase in the expression of different proteins, including GFAP (23,24). A neutralizing antibody against the FKN receptor (AbCX3CR1; 10 μg per DRG) was administered into the DRG (L5).…”

Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice

“…Conversely, blocking the activity of certain inflammatory cytokines in DRG partially relieves the CCD-induced hyperalgesia [16,17] . In addition, increased activity of satellite glial cells in the DRG has been recently shown to play an important role in CCD-induced neuronal hypersensitivity [18] . However, the mechanisms underlying the spread of mechanical and thermal hyperalgesia as well as mechanical allodynia observed in CCD mice remain still unclear and require further investigation.…”