Glia cells comprise 90% of the cells in the nervous system. The other 10% of cells consists of neurons. In the artist impression we see the high number of glia cells for each separate neuron.

The word 'Glia' is derived from the Greek word for "glue" giving the impression that the main function of these cells is to keep the brain from running out of our ears. (Bear M.F. Neuroscience, exploring the Brain 2007 3rd ed.)

Glia cells are thought to insulate, contribute and nourish neighbouring cells. Recently, more and more knowledge has been gained in the role of glia in neuropathic pain. Glia seems to play a much more important role than anticipated, hence the term 'gliopathic pain'. Glial activation is required and sufficient for chronic pain sensitization, the root cause of neuropathic pain.

The pathogenesis of neuropathic pain involves not only neuronal pathways, the target for the classic anti-neuropathic drugs for decades, but also non-neuronal cells such as the Schwann cells, satellite cells in the dorsal root ganglia, peripheral immune cells, mast cells, spinal microglia and astrocytes. ^[1][2]

This is the reason why scientists working at the frontier of neuropathic pain are starting to shift their attention from neuronas to these non-neuronal cells and their importance in the pathogenesis of neuropathic pain:

As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain.^[3]

We will discuss some of these cells in more detail and feel that the term gliopathic pain is better to capture the chronic pain than the now used term neuropathic pain. 

Astrocytes 

The most numerous glia cells are the astrocytes, filling in the spaces between neurons. Astrocytes constitute 40% to 50% of all glial cells. Another name for astrocytes is astroglia. These cells are small and measure about 20nm. They play an essential role in regulating the chemical content of the space in between the neurons.

Unlike microglia and oligodendrocytes, astrocytes form complex networks and are closely associated with neurons and blood vessels. A single astrocyte enwraps 4 to 6 neuronal celbodies and contacts 300 to 600 dendrites. 

The astrocytes, in enveloping the synapses of adjacent neurons, preventing and regulating the spread of neurotransmitters. Astrocytes can remove actively the neurotransmitters from the synapses. Also the neurotransmitter glutamate, which is an activating neurotransmitter, is regulated in its concentration by these cells.^[4][5]

Astrocyte activation in neuropathic (gliopathic) pain is measured via glial fibrillary acidic protein (GFAP) upregulation and astrogliosis, hypertrophy of astrocytes, are enlarged cell bodies and thick processes. The active astrocytes with gliosis are also called reactive astrocytes, and these cells play a key role in neuropathic pain.

Asterocyte metabolism and function is a new target for drug development. ^[6]

Myelinating Glia (oligodendroglial and Schwann cells)

Oligodendrocytes, which are derived from neuroectoderm, produce myelin to ensheath neuronal axons. The function of these gliacells seems clear. These cells envellop the axon and the dendrite of the cell, and support in this manner the electrical impulse of the nerve cell. Space in between tho envelloping gliacells create a node of Ranvier. This facilitates a faster electrical current through the nerve fiber. When a peripheral myelinated nerve is cut, schwann cells guide the regrowing of the axons.^[7]

Microglia

Microglia are the garbage men of the neuronal network. They are the resident macrophage-like cells of the CNS. These cells are phagocytes removing debris and degenerating neurons and glia. Around 15% of all cells in the nervous systems comprise of microglia.

Satelite glia

Authosr: David J. Kopsky, MD and Jan M. Keppel Hesselink, MD, PhD Ocobter 2010

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