GLIAL CELL FUNCTIONING IN NEUROPATHIC PAIN

 Chronic pain, a pathological state, affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying the creation and maintenance of enhanced pain states after injury or inflammation remain far from clear. In the last decade, however, the discovery that glial activation amplifies pain has challenged classic neuronal views of "pain". This review focuses on recent developments in understanding that spinal cord glia are involved in pathological pain. We overview the action of spinal glia (both microglia and astrocytes) in several persistent pain models, and provide new evidence that spinal glia activation contributes to the development and maintenance of arthritic pain facilitation. 

We also attempt to discuss some critical questions, such as how signals are conveyed from primary afferents to spinal glia following peripheral nerve injury and inflammation. 

1. What causes glia to become activated after peripheral/central injury/inflammation? 
2. And how the activated glia alter neuronal sensitivity and pain processing? 

Answers to these questions might open a new approach for treatment of pathological pain

http://www.ncbi.nlm.nih.gov/pubmed/18471878/ 

The central nervous system consists of neurons and glial cells.  

Neurons constitue about half the volume of the CNS and glial cells make up the rest. 

A NEURON

Glial cells provide support and protection for neurons.  They are thus known as the "supporting cells" of the nervous system.  

The four main functions of glial cells are:

1. to surround neurons and hold them in place,
2. to supply nutrients and oxygen to neurons
3. to insulate one neuron from another
4. to destroy and remove the carcasses of dead neurons (clean up).

The three types of CNS supporting cells are 

1. Astrocytes
2. Oligodendrocytes
3. Microglia.

Astrocytes:  Astrocytes provide physical support to neurons and clean up debris within the brain.  

• They also provide neurons with some of the chemicals needed for proper functioning
• Help control the chemical composition of fluid surrounding neurons. 
• Finally, astrocytes play a role in providing nourishment to neurons.

In order to provide physical support for neurons astrocytes form a matrix that keep neurons in place.  In addition, this matrix serves to isolate synapses. 

This limits the dispersion of transmitter substances released by terminal buttons; thus aiding in the smooth transmission of neural messages, by neurotransmitters...the brain chemicals, that essentially act as messengers by passing communication from cell to cell at the right time, speed, etc

Astrocytes also perform a process known as phagocytosis.  

Phagocytosis occurs when an astrocyte contacts a piece of neural debris with its processes (arm of the astrocyte) and then pushes itself against the debris eventually engulfing and digesting it.

Astrocytes provide nourishment to neurons by receiving glucose from capillaries

Breaking the glucose down into lactate (the chemical produced during the first step of glucose metabolism)

Releasing the lactate into the extra cellular fluid surrounding the neurons.  The neurons receive the lactate from the extra cellular fluid and transport it to their mitochondria to use it for energy.  In this process astrocytes store a small amount of glycogen, which stays on reserve for times when the metabolic rate of neurons in the area is especially high.

The principle function of oligodendrocytes is to:

• provide support to axons and to produce the Myelin sheath, which insulates axons. 
• Oligodendrocytes unlike Schwann cells of the PNS, form segments of myelin sheaths of numerous neurons at once. 

Microglia are the smallest of the glial cells. 

• Some act as phagocytes cleaning up CNS debris.
• Most serve as representatives of the immune system in the brain.
• Microglia protect the brain from invading microorganisms and are thought to be similar in nature to microphages in the blood system. 
• Myelin is 80% lipid and 20% protein and allows for the efficient conduction of action potentials down the axon.  
• The processes of a given  wrap themselves around portions of the surrounding axons.  
• As each process wraps itself around, it forms layers of myelin. 
• Each process thus becomes a segment of the axon's myelin sheath.

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The supporting of the PNS (Parasympathetic NS) are known as Schwann Cells.

Schwann cells are the supporting cells of the PNS.  Like oligodendrocytes schwann cells wrap themselves around nerve axons, but the difference is that a single schwann cell makes up a single segment of an axon's myelin sheath.  Oligodendrocytes on the other hand, wrap themselves around numerous axons at once.

In addition to creating the myelin sheaths of PNS axons, Schwann cells also aid in

• cleaning up PNS debris
• guide the regrowth of PNS axons. 

 In order to do this Schwann cells must be able to:

• Arrange themselves in a series of cylinders that serves as a guide for sprouts of regenerating axons.
• If one of these sprouts encounters a cylinder the sprout will grow through the tube at the rate of 3-4 mm per day.
• Nonproductive sprouts simply wither away. 

http://blustein.tripod.com/index.htm/