GLIAL ACTIVATION IN NEUROPATHIC PAIN

Glial Activation In Neuropathic Pain

In almost a counterpoint to the above noted mechanisms of neuropathic pain, it has been reported that astrocytes and microglia in the CNS/spinal cord can be activated and induce the creation and maintenance of pain facilitation secondary to inflammation and damage to peripheral nerves, other peripheral tissues, spinal nerves, and the spinal cord. Glial cells appear to be of immune cell origin.

Glial activation can occur via a number of processes:

·         bacteria and viruses that bind to specific receptors expressed by both microglia and astrocytes; substance P,

·         excitatory amino acids (EAAs),

·         fractalkine [a unique chemokine expressed by neurons; its only receptor is expressed by microglia ] and ATP released by A-δ and/ or C fibers presynaptically or

·         by brain to spinal cord pain enhancement pathways;

·         as well as nitric oxide,

·         prostaglandins, and fractalkine released from “pain transmission neurons”.

o   After the microglia and astrocytes are activated, they induce hyperexcitability from nociceptive neurons and increased release of substance P and EAAs from the presynaptic terminals.

o   These changes are helped by glial release of nitric oxide, EAAs, prostaglandins, proinflammatory cytokines such as interleukin-1 and -6, tumor necrosis factor, and NGF.

So, following this

• These changes create the presence of continuous “pathologic pain”.
• Research indicates that intrathecal gene therapy driving the production of inter-leukin-10, an anti-inflammatory cytokine, can stop neuropathic/pathologic pain.
• Finally, data suggest that in response to morphine, glia release neuroexcitatory substances, causing opposition to morphine‘s analgesic effects.

Complex Regional Pain Syndromes As Neuropathic Pain

o   Following peripheral nerve injury, concomitant alternations may be evident in dorsal root ganglia, including transmitter changes and increased density of sympathetic nerve terminals.

o   Tyrosine hydroxylase positive cell terminals that produce norepinephrine migrate from vessels supplying the dorsal root ganglion to nerve ganglion cells following sciatic nerve injury.

The dorsal root ganglia then express a-adrenergic receptors. ...

1. Original injury carrieis pain impulse to sympathetic Nervous system by sensory nerves
2. The pain impulse in turn triggers in the SNS which returns to the original site of injury.
3. The SNS impulse triggers the inflammatory response causing the vessels to spasm leading to swelling and  increased pain.
4. The pain triggers another response, establishing a cycle of pain & swelling à Resulting condition with burning pain red and/or mottling of the skin and the myriad of other symptoms of RSD/CRPS