It helps to be able to think in concrete terms to figure out what is happening in central pain.
This author had an interesting discussion with one of those doing computer design for Segway in New Hampshire. You have seen the Segway. It is the platform with a handle, that looks like a push mower, which neatly transports people around. We see the trendy device in use at the college campus nearby. The only problem is that you can’t take your girlfriend with you as you go. (Johnson and Johnson makes a wheelchair that works off similar principles).
Now what is significant about the Segway (which is due to hit Sam’s Club soon), is that it uses electromagnetic torque to drive a motor at each wheel. As you lean forward, more forward torque is applied. As you stand more upright, the forward torque continues but there is also some reverse torque being applied. Feedback loops are at the heart of what is called “integration”. Forward torque could be compared to excitatory pain impulse, while reverse torque could be compared to inhibitory pain signal. Central pain is “dis-integrated” pain.
Sensation is much the same way. Excitation and inhibition of signal are always going on simultaneously in the cord. In the normal individual, they are in balance. In central pain, they are out of balance. In the normal state, as a nerve is signaling pain, the brain inhibitory force is doing some inhibition to keep things in check. We have already described how the brain inhibitory force is eliminated in central pain. This one sided pain system makes for the spontaneous burning, lightning pains, etc. which occur without any stimulus being applied. The brain’s inhibition is applied inside the cord by interneurons, which intrude on synapses between FIRST ORDER neurons coming in from the body and SECOND ORDER neurons near the level of entry, which then go up to the thalamus. Interneurons are poised BETWEEN the FIRST and SECOND order neuron, like policemen, to keep order.
Within any neuron, there is another balancing going on, that of the chloride ion and other negatively charged anions which balance against positively charged cations such as sodium, potassium, and calcium. Anions (negative charge) are inhibitory, while cations (positive charge) are excitatory in the neuron.
With brain and neuronal inhibitory mechanisms, we have dual inhibition:
1) The brain’s natural tendency to ignore noise and to reduce pain through direct signaling by interneurons
2) The inherent tendency of chloride ions to reduce firing at the cell membrane of the neuron.
Inhibition by the brain is eliminated in CP because injury to the CNS neuron causes release of Nerve Growth Factor (an event aimed at repair). NGF in the glia causes production and release of brain derived neurotrophic factor (BDNF). BDNF has the unfortunate effect of blocking gamma amino butyric acid (GABA), which is the chemical used by the CNS to INHIBIT pain signal. This takes the brain inhibition out of the equation!
Within the neuron, an injured nerve cell cannot produce sufficient quantities of KCC2, which is the protein carrier for chloride ion
(Cl-).
When KCC2 (the carrier of Cl-) is low, chloride is NOT moved to the neuronal membrane. When chloride is taken out of the picture, ANY action potential (nerve impulse) will be excitatory, even if it was originally supposed to be pain inhibitory (reversing the nature of the neuron spike is termed “anion reversal”). Please see comments on anion reversal at this website by a contributing author, Jeffrey Coull. Coull is the brilliant Canadian researcher who discovered anion reversal, ie. conversion of any inhibitory signal to an excitatory impulse when chloride ion cannot act at the cell membrane.
When you compare the pain system to a Segway, you realize that central pain is always going to be leaning forward, with no reverse torque being applied. This is one way to think of how spontaneous dysesthesia, a burning pain, occurs in the CP subject. Protopathic burning is the last sensation to leave when a nerve is deprived of oxygen. Burning is the most durable of the pains, and so manifests the most strongly, although other central pains intrude into the sensorium as well (eg. lightning pains, pins and needles, muscle pains, bladder or gut filling pain etc.).
So the next time you see a neat little Segway flashing some student across campus, you will reflect on the advantages of being able to bring the thing to a halt. Unfortunately, you cannot do this with your pain system, because reverse torque has been disabled.
