This blossoming field is going to be very important in understanding what happens to the injured cord to cause Central Pain. Brain Science is fun. Central Pain is agony. Let’s get these two together quickly.
Scientists are struggling their way through the sialic acid cycle and there is no better evidence that this is research whose time has arrived than the article on C fibers by El Maarouf et al from Sloan Kettering in the July edition of the Proceedings of the National Academy of Sciences.
It will be hard to keep this non technical, but you deserve to know what is going on. It has now been found that sialic acid prevents the disconnect of C fibers from their targets in Lamina II of the dorsal horn of the cord. Nociceptive C terminals lose their connections in chronic neuropathic pain. This “deafferentation” or loss of input via these connections is thought to be read by the brain as an injury and to initiate the changes which lead to central pain. Sialic acid has NO effect on A beta touch or on allodynia. The C fiber effect is related solely to THERMAL hyperalgesia.
It is a very complicated world then, to speak of central pain relief. Therapy may have to be individualized to the patient, all the more reason for you to complete the survey at this site so we can inform the medical community of the reach and range of the central pains.
Sialic acid is one of the sugary proteins which stick out from the surface of cells and lead to cell-cell recognition, adhesion, interaction, and plasticity (ability to change). It occurs as a polymer, or long chain of repeating units, and is most associated with certain molecules, called nerve cell adhesion molecules or NCAM. These sugary chemicals in some of their elaboration have been found to be identical to the b group gangliosides. “Gangliosides” is a name given to glycoproteins on cell surfaces found in the brain. Human diseases are known when GM1 or GM2 ganglioside build up to unacceptable levels. A competing sugar can block GM1.
Synthetic GM1 ganglioside is already being used in trials to prevent or minimize spinal cord injury and promote healing (unproven as yet). Myelin Associated Ganglioside (MAG) is thought to be responsible for blocking repair of injured spinal cord neurons. And so we see a huge area for study opening up. These things are not just glue, because the composition of our sialic acid chains is one of the things which makes us more intelligent than other creatures. Apes have an OH group attached to their sialic acid which keeps them from reaching the brain efficiency of humans. On the evolutionary chain, sialic acid chemistry is VERY important, and it appears to be VERY important in our inability to repair neurons. It may be possible to stop central pain by tweaking sialic acid chemistry through altering substrate, ie. the sugars which become part of the glycoprotein. (Glycoprotein is a sugar plus a protein).
Giving sialic acid to cord injured rats helps the C fibers reconnect in the cord, but this leads to hyperalgesia, a paradox for the present time. As if this were not sufficient to arouse our curiosity, sialic acid has now been studied with regard to the AMPA receptors which respond to glutamate, the major pain exciter in the human nervous system. (See the many articles on AMPA using SEARCH, at this site) AMPA is short for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and the glutamate receptors is known as AMPA-R. (AMPAr is usually refers to HUMAN glutamate pain receptor, with the name of the animal usually prefaced when lab animals are referred to, as in rats or guinea pigs).
Polymerized sialic acid, or PSA, grown from bacteria prolongs the open channel time of AMPA-R mediated currents several fold. This means more pain. What we need to figure out is how to restore the C fiber connections in the dorsal horn of the cord, but prevent the hyperalgesia which sialic acid maintains.
The voltage gated sodium ion channels are known to be rich in sialic acid, but it has not yet been studied how this changes in the Nav1.8 fetal ion channels which are produced in subjects with central pain. Presumably this all connects together, to contribute to the central pains. As always, the vocabulary is deficient. It is tricky to refer to thermal hyperalgesia, since CP patients have LOSS of the ability to detect temperature change yet suffer, after a sufficient time to perceive the heat, from thermal hyperalgesia. What they really have is ongoing spontaneous burning, for which there is no particular term except burning dysesthesia. There are gaps in the terminology, and clinicians constantly get confused at what we are saying. This site attempts to clarify, but it is not an easy go for us or for you. Your completion of the survey helps us tremendously.
Some of the paradoxes of pain (heat plus cold in the dysesthetic burning, periodicity of certain central pains, failure of discriminative features in dysesthetic burning etc.) may well have their origin in the sialic acid pathways which involve both transferases and kinases, to control and regulate sialic acid production.
Although the whole concept is an oversimplification and does not account in the entirety for the difference in intelligence between apes and man, the greater efficiency of human Neu 5 Ac (sialic acid related molecule) WITHOUT a hydroxyl group is very interesting. The diagrams below show the Neu 5 Ac which makes humans intelligent, and compares it to the lower diagrammed Neu 5 Gc configuration, with an extra OH group at the lower left of the structure, which is found in apes and limits their intelligence.
You can view the diagram here.
These glycoproteins determine to a considerable degree the efficiency of cell cell interaction and confusion and disorder in the sialic acid pathways is felt to be related to deafferentation, central pain, and hypersensitization. The abnormal growth of neurons in the cerebellum of developing humans when NCAMs are blocked is not understood but is considered further evidence that our brain cells MUST be able to connect and speak to each other normally for normal transmission. The best bet currently is that the brain, possibly via the thalamus, reads abnormal sialilyzation as a pain message. Hold onto your hats, the scientists are off and running again on molecular pain mechanisms.