DocCornerThe title of this piece sounds slightly reminiscent of a horror movie and it is intended that way. Not long ago, I accidentally got bleach on my hand. In a minute or so it was uncomfortable so I washed it off. It had caused a burning feeling. There have been similar incidents in life, such as contact with drain cleaner, or that time in the laboratory in college when the student across the table splashed acid on my hand. Chemical burns have a characteristic feeling, which is not exactly like other burns. Central pain is caused by an accumulation of natural acids in the body, which cause the pain fibers to “burn”.

Nature does not have one concentrated acid that it uses to initiate pain messages. Such a substance would be hard to control and need a lot of little storage containers. Instead, nature combines many weaker substances to create an acid chemical soup that is quite strong. Remember that the body is homeostatic, that is, it likes to keep things the same. That is why the water concentration, temperature, and pH (acid base balance) of our bodies are usually very stable. The scale of acidity goes from 0 to14. If a healthy newborn has a body pH of 7.38, that means the baby is slightly non-acid (alkalytic), which is good. If something causes the baby’s pH to fall to 7.20, brain damage is a very real possibility. Fortunately, the body likes to remain stable.

The chemical soup of pain, however, can drop the pH at nerve endings as low as 5 or 6, which is very, very acid for a human body. It hurts. It burns. The nerve doesn’t like it and immediately sends a pain signal to the brain.

Production and activation of chemicals like prostaglandins, kinins, cytokines, potassium, and other ingredients of the chemical soup is controlled by proteins that are often kinases, meaning they attach a high energy phosphate bond to the chemical to make it active. Kinases themselves are under genetic control. Some scientists think that if too much acid is applied to a nerve for too long a period, causing the pH to be too low for too long, the genes in the nerve cells lose their control mechanisms and begin to pour out pain chemicals without regulation. This may be the core of what is happening in central pain.

The discovery that nerve acidosis was fundamental to pain is a recent happening[1]. These acids at the nerve endings beneath the skin were first found to be major players in pain. Next was the astounding discovery that many of these same chemicals are present in the nerve ganglia at the cord entry area, or even in the cord itself, where the first synapse occurs. Acid was present at step one and at step two. Then, very recently the discovery was made that at the second synapse, in the thalamus itself, right in the brain, this same group of chemicals forms acid to perpetuate the pain signal. Why was this surprising to scientists? It was unexpected, because the chemistry of the brain is generally different from that found in nerves elsewhere in the body.

Nerve acidosis as a universal aspect of pain was surprising in the extreme. This left scientists looking at several possible ways of stopping central pain, but it also made the problem more complex, since it would be necessary to solve the acid problem in three places, below the skin, in the cord, and in the thalamus. The thalamus sits at the midline of the brain, with one half on each side of the midline. It is in control and the cortex, the 2mm of gray matter that sits atop the brain, is driven by driver signals (driver afferents) from the thalamus.

So far as it known, central pain is a disease of the thalamus, no matter where the central nervous system was injured in the first place. It is a form of brain damage. One hundred years ago it was called “thalamic pain,” but now it is called “central pain” saving the term “thalamic pain” for those whose injury in the first place was specifically from a stroke near the thalamus. Roughly speaking, central pain from brain injury is almost identical to central pain from cord injury, but there are a few differences. Nerve injury pain out in the peripheral nerves of the body can also cause similar symptoms, but the differences grow much greater when comparing central and peripheral nerve injury.

Central pain usually is much more severe than peripheral neuropathy, although some peripheral neuropathy is ghastly, and central pain is usually much more elaborated, meaning there are many more components to the pain and it reaches many more systems (typically skin, muscle, gut, and bladder sensation are made painful). Normally in the cord, sensation travels up the back and motor nerves travel down the front. The exception is pain, where for unknown reasons, nature elected to place the pain tract (spinothalamic tract) in the front, among the muscle fibers. It is not known if spillover in irritability in the spinothalamic tract is the reason so many people with central pain also have pain in the muscles, but for some the pain is so severe that they are functionally paralyzed.

Muscle pain is thought to come from the sensory arm of the spindle apparatus (the gamma motor system) which informs the brain of the state of contraction of muscle bundles, since the pain is described as being like a cramp, a drawing, or tightening. In multiple sclerosis, which can affect the central nervous system almost anywhere, this tightening is frequent and often felt in the chest, where it is called “MS Hug.” However, the muscle pain of severe central pain is usually so bad that “torture” is more appropriate than the word “hug.”

In the body, nature shows great efficiency. For example, only a limited number of neurotransmitters are used to excite or inhibit nerve cells. For example sympathetic nerves (fright and flight reactions) generally use norepinephrine to stimulate, but the parasympathetic nerve cells favor acetyl choline. Is this important? Yes, because depending on where you are in the nervous system, the same chemical can be an exciter or an inhibitor. Nature keeps track and in a marvelous alternation of locations, uses the small number of neurotransmitters to accomplish a very complex excitation or inhibition of signal. Most of what the central nervous system does is inhibit, suppress, and filter signals, so that we can think of only one thing at a time. When damage occurs that is short of total destruction, the greatest failure is in the inhibitory apparatus. In pain nerves the result is nerve injury pain, or neuropathic pain. If this injury is in the central nervous system (brain and cord), the condition is known as central pain.

Nerve cells receive input from thousands of other fibers and decide whether to ignore or to transmit on a signal, which in turn influences higher level nerves to fire or not fire. A nerve cell cannot fire more strongly. The amplitude (strength) of firing is fixed. It can only fire slower or faster. The strength of a pain signal is determined by the frequency of firing. What then are the things that can influence the frequency? We do not know all the factors.  We do know that for every nerve cell or neuron in the brain there are about three other cells, known as glial cells, which chemically influence the signal as it moves through the system. Nerve cells are actually rather poor conductors of electricity as it turns out. Nature solves this by providing a booster at very small distances apart. These boosters are influenced by the signal that manages to reach them and then they generate a new signal or “action potential.” The outside of the cell is 40-90 millivolts more negative than the inside. Think of the positive and negative ends of a battery. Current that flows reduces the difference in voltage potential and reduces the polarity. As it does this, the booster fires off an action potential that may reach the next booster. Eventually, at the end of the nerve fiber a gap is encountered, known as the synapse. Chemicals that have been waiting in little vesicles, or pockets, are released to make the jump to the next neuron. Neurotransmitters concentrate at the synapse.

The two pain exciter neurotransmitters are, not surprisingly, acids. They are the two amino acids that are acidic; glutamate and aspartate. Surprisingly, most amino acids are non-acidic. Glutamate controls quick pain. Aspartate is involved in longstanding pain. Both can act together, of course.

At the far side of synapses are deposits of n-methyl-D-aspartate (NMDA). This is the devil. It does not normally participate much in the pain process, but is held back in favor of other, less potent tormentors. In central pain, however, NMDA packets are broken open, activated and resupplied like mad. It results in unremitting torture. Further sensation such as heat, cold, touch, or whatever heightens the process, adds fuel to the fire. This extra pain over the resting state is called “evoked pain,: which just adds to the torture. N-methyl-D-aspartate is more powerful than the human spirit. It is merciless when uncontrolled, a chemical sadist. NMDA has been nicknamed the “Non-merciful damnable acid.”  The chemicals that activate NMDA are called collectively the “mitogen activated protein kinase” cascade or MAPK.

If you have central pain, you have become one of the people of the acid. You need help. You must not let anyone try to talk you out of your condition and set you up for a suicidal failure by imposing expectations upon you which you cannot meet. Your limitations will manifest soon enough to reveal the lie to anyone who thinks severe CP can really be endured. The price exacted is your own identity. You will lose many of the mental traits which make you who you have been and you will become someone new, someone afraid.

Nearly everyone knows of Pavlov’s dogs who learned to salivate at the sound of a bell. Few know that after the famous experiments, the basement where they were kept in wooden cages flooded. In the morning, the dogs were found with just their noses floating above water. Pavlov himself was stunned to find they no longer salivated at the sound of a bell. Furthermore, they could never again be taught to do so. Something in their brain was changed.

Central pain is that kind of condition. It never leaves the patient the same. You cannot have the same expectations of yourself. Whether or not others are willing to cut you some slack, YOU have to learn to conserve your diminished resources in order to survive. There are things you could do before which you cannot do now. You will have to accept that or find yourself in the pit of depression. Just as it would not do for a paralytic to expect to win an Olympic dash event, the CP patient cannot expect to relate to others as successfully as if they were not suffering ineffable pain. You must accept this and you must find another way to go on.

If you are wise, you will spend a great deal of effort trying to write to Senator Harkin of Iowa who chairs the Senate subcommittee that oversees spending at the National Institutes of Health. Write your own senators and congressmen as well. Ask them to lobby Sen. Harkin to fund basic pain research at NIH (National Institutes of Health).  Central pain does not usually respond to opioids (like morphine and Demerol), which inhibit pain at the cord level but may actually increase it in the brain by inhibiting inhibitory tracts (this is called “disinhibition”). There is NO satisfactory treatment for central pain. Still, you need the help of a good pain clinic for sedation, support, and validation.

Some of you may be subsisting on false hope you will find a cure soon if you just spend enough money or have enough surgeries. Cases resulting in a cure of central pain are exceedingly rare and usually mean the nerves have died entirely, not gotten better. You may feel very, very lucky and hope this will happen to you. However, sooner or later you will likely have to face the realization that if scientists do not do something, nearly all of us face the prospect of many years with severe pain.

[1] Yaksch, Tony, Pathophiology of Nociceptive and Neuropathic Pain