Introduction to Neuropeptides

A field almost as vast as outer space may still yield the answer to pain.

Computer function sometimes gives a model for understanding the nervous system. For example, although your computer may be working, you still need specific driver software to operate peripheral devices like scanners and printers. Neurotransmitters facilitate nerve activity but require neuropeptides to drive complex activity. Much of nerve facilitation involves the activation of kinases, which energize chemical reactions. Without kinases you just can’t start the show.

This context prepares us to talk about neuropeptides. Amino acids can be grouped in long chains (over 200 a.a.) to form proteins, or they can be arranged in shorter sequences to form peptides. A neuropeptide is any peptide that affects nerve activity, so there are a lot of them. Simple amino acids or their variants may themselves be neurotransmitters. Glutamate ezcites nerve activity. A close cousin, Gamma-amino-butyric acid (GABA) inhibits activity.

It is important to remember that the talk about neurotransmitters can miss the point. The NAME of the neuropeptide can be deceiving, for it may relate to the first discovered function, which may not necessarily be the one related to the nervous system. An example of this is the vasoactive intestinal peptide (VIP), which is a potent neuropeptide, as well as impacting vessels in the body.

The body is economical and will use neurotransmitters in more than one activity, but the specific action that results depends on WHICH RECEPTOR FOR THE NEUROTRANSMITTER IS INVOLVED. So don’t get hung up on the neurotransmitter although which one the body uses can suggest which receptors will light up.

A model for neuropeptide activity is found in the Aug 2004 article in Neuron by Yu.

Don’t get discouraged at the terms scientists use. They will become familiar. (Names are not as important as processes).

Serotonin you have heard of.Scientists know it as 5 hydroxytyptamine, or 5HT.

Protein Kinase A is the kinase which attaches high energy bonds to permit long term facilitation of sensory neurons. There is a neuropeptide which is activated in this process, called sensorin.

When sensorin is activated, then another kinase, known as mitogen activated protein kinase begins to enter the nucleus of sensory neurons, where it helps translate DNA messages into the production of proteins which increase firing power at the nerve gap, or synapse.

Interestingly when 5HT gets this process started, many small blood vessels are induced to grow or to enlarge in the area before the synapse. Many pain chemicals are related to the behavior of blood vessels.

The inner lining of blood vessels is known as the endothelium. The endothelium is where the activity of pain chemicals is going on. You cannot separate pain chemicals and long term facilitation of pain from the growth of small blood vessels, because they go together at the synapse.

And so science has abandoned the old idea of pain as a simple operation. It is massively complex, and related to learning, negative emotion, and environmentally stressful events.

Descartes compared pain to the bellrope by which he could signal servants on the floor above. This would have made things a lot easier for the neuroscientist if it were the case, a simple, line wired process. Nothing could be further from the truth, but if Descartes can be fooled, then you can forgive your friends who suggest simplistic ideas about pain. Pain is very complex in its chemical processes, but the body does such a good job integrating pain features that it comes out as the clearest complex signal in the nervous system.

With enough pain, you forget about everything else. Almost without thinking, you know WHEN the pain started, WHERE it is, WHAT kind of pain quality is present, and you probably have tried to avoid the pain even before you could eben think about it. This clarity, or marvelous integration in pain, fools people into thinking it is a simple matter.

The complexity of pain mechanisms is large facilitated by neuropeptides. There appear to be many spots at which pain can be modified or blocked. As applied to Central Pain, we hope to soon find a way to stop the tremendous increase in the sensitivity of pain neurons, so that they stop firing at almost anything.

Not only do they fire to light touch, but apparently they are so sensitive (hyperalgesic) that they fire even at the random low level of neuron “noise” which is always present in the nervous system from the kinetic energy of heat. If you could listen to the sound of action potentials firing random volleys along the nerves, you would wonder how the brain can make sense out of that racket. The racket is there to keep the neurons ready to fire, almost at the point of depolarization. Sometimes a neuron jumps over the line. And that is where noise comes from in the nervous system.

It is not true that we only use five percent of our brains. We use all of the neurons all the time, but the brain has the power to ignore them until certain patterns of meaning to the brain are detected. How does the brain acquire templates or pattern recognition skills?

Scientists wonder this too. It seems neuropeptide algorhythms help with the process of inhibition and excitation. In nerve injury, the gene controls of the neuron are altered, possibly by growth factors, and pour out chemicals that upset the normal process, making the nerves unreasonably sensitive. It would appear that nieety five percent of brain function is not about doing things, but inhibiting the noise. This noise keeps the nerves at greater readiness to fire but requires tremendous inhibitory activty to make the nervous system function. Central Pain appears to be a failure in that inhibitory ability. Like many things in the body, you wouldn’t have guessed it, but Nature surprises us in a lot of things.
Kinases are enzyme like chemicals which attach high energy phosphate bonds to other chemicals, which are in a quiet state before activation. Phosphate bonds are the batteries for the bodies chemicals. This system allows cells to store chemicals until they are needed.

Synapses are found between nerves. They are gaps where the nervous sytem can decide to apply exccitation or inhibition. Activity at the synapse determines whether the signal will continue onward and whether other nerve fibers wlll be recruited to send a smiliar message so that the brain pays more attention. If the brain considers the message important or unimportant, it can excite or inhibit at the synapse. There are about three synapses in the pain circuit between the skin and the thalamus in the brain.

Amino acids are comparatively simple molecules based on carbon, which generally include nitrogen and oxygen. These are standardized, and the human body uses less than thirty of these to make all of life’s processes happen. You might think thirty is not so many but if you begin to study it, you may wish there were less than thirty.