July 2019 Edition. Volume XIX

The means by which neurostimulation influences the intact nervous system to produce pain relief is presently not known.  The reason for this is that our understanding of the neurochemistry and neurophysiology of the nervous system is still primitive and really hasn’t progressed much beyond the original “phlogiston” theories. There do exist, however, a number of plausible theories which we now accept as being reasonable.  These have provided guidelines by which  acceptable management of pain by neurostimulation can be applied.


In early times pain was thought to be a reflection of the body part receiving “phlogiston” from its proximity to fire.  In this illustration, published by Ren Descates (1596-1650) in 1644, the “phlogiston” is said to set a spot on the skin in motion, pulling then on a thread traveling through the body to the brain where a bell strikes.  This theory was not challenged until the work of Antoine Lavoiser between 1770 and 1790.

The term “phlogiston”derives from the Greek tem for “burned.”  When chemical theories were first being advanced, the phenomenon of fire (combustion, now known to be oxidation) was elucidated by the sages as representing the liberation of a substance referred to as “phlogiston.” It was not until the 17th century that this theory became obsolete.

Perhaps the first modern concept relating to the nervous system as a “traffic manager” for pain information was the work of Glen Player who published his treatise on the “Obscuration Phenomenon” in 1952.  Player’s work formed the conceptual framework which then led to the development of the “Gate Theory of Pain.”

The “Gate Theory of Pain”


When Ronald Melzack and Patrick Wall published their treatise on the “Gate Theory of Pain” (Melzack R, Wall PD: Pain Mechanisms: A New Theory. Science 9:159-971, 1965) it was of particular value in unifying the prevailing concepts regarding the nature of pain and also served as a reasonable explanation of the observations of the clinical community regarding the means by which electrical stimulation could influence the nervous system.  The concept of a railroad switching station opening to the favored area of afferent (input) information was simple and seemed appropriate and served the need for a rational explanation relating to observed phenomenon.

DorsalColumns 300

It was well appreciated by the 18th century that the spinal cord highway by which sensory information from the body itself were the dorsal horns of the spinal cord (shown with green dots).  It became evident to neurosurgeon C. Norman Shealy that electrical stimulation of these structures would be a likely means of modulating pain.

In regard to the phenomenon of neurostimulation the Gate Theory of Pain explained only part of the observed effect.  In most cases, following a period of induced spinal stimulation, patients often experienced pain relief continuing for hours.  The refractory period following stimulation could not account for this.  It seemed clear that the stimulation also exerted some effect on the neurohumoral status of the brain allowing for neurotransmitter or neurohumoral response.  The theory of release of endogenous opiates serves well to explain this observed effect.


Endorphins represent a class of neurotransmitters normally produced by the human brain (endogenous opiates).  These natural substances are important to our well-being because they mediate a sense of well being as well as pain relief.  When patients receive narcotic medications, such as morphine, for the purpose of pain relief the production of endogenous opiates is blocked and thereby decreases.  An important role of neurostimulation is to release these stored endorphins.  Endorphin release appears to provide the phenomenon of continued pain relief after cessation of actual stimulation.

NSPain1The storage of endorphins can be likened to a brain reservoir where electrical stimulation acts to “open the gate” and allow release of these stored neurotransmitters.  If endorphin production has been suppressed “opening the gate” of an empty
reservoir has no pain relief effect.  

Regional Complex Pain Disorders

Pain200GIFThere is no disagreement with the observation that pain can be totally disabling.  Most pain however fades, by the process of healing, following initial insult.  There are some types of pain which are particularly cruel and incapacitating and constant in nature. They are, in fact, referred to as “agony” rather than pain because of their unique nature.  These pain variants are described by the sufferers as being “constant, burning, and agonizing” in nature.

These forms of agony have been given a number of distinguishing labels such as “causalgia” and “reflex sympathetic dystrophy” as a means of differentiation.  Because there are so many variants the term “regional complex pain disorder (RCPD)” has been advanced by dolorologists (those who study the diagnosis and treatment of pain disorders) as a means of more accurately describing these phenomena. In order to understand the RCPD one must travel back in time to the Civil War in the United States where, due to man’s inhumanity to man, legions of marching men suffered terrible wounds.  S. Weir Mitchell (1829-1914) a Union army surgeon from Philadelphia, specializing in neurology, recognized that many soldiers with partial severing of extremities developed a unique type of pain which he termed “causalgia” (Mitchell SW, Morehouse CR, Keen WW: Gunshot Wounds and Other Injuries of Nerves. JB Lippencott: Philadelphia, 1864<).

Causalgia  was seen when peripheral nerves were only partially severed.  It seemed that because there was a different pattern of afferent information traveling to the brain that this pattern of neuropathia was perceived by the brain as being an extremely disagreeable sensation which was uniquely disabling. Because these injuries often involved somatic as well as autonomic systems (as well as vascular impairment) they were difficult to sort out.  In fact, later study suggested that causalgia seemed to be a phenomenon of the paleospinalthalamic (phylogenetically old pain system) of the body as opposed to the neospinalthalamic (phylogenetically new pain system) as discussed below.

Some of the most consistent aspects of  RCPD is its associated high level of disability as well as its great resistance to effective treatment.  In fact, the single most successful treatment (over the past 3 decades) has been the use of implanted neurostimulators in carefully selected patients.

While the Gate Theory of Pain clearly identified the brain as the active system responsible for filtering, selecting and modulating sensory afferent information we still are left with the challenge of dealing with a structure about which our knowledge is clearly of a rudimentary nature.  As a means of beginning to make sense of this Ronald Melzack (McGill University) has proposed the concept of the body-self neuromatrix.  This implies that the brain possesses a dynamic neural network which is constantly integrating and interpreting a myriad of afferent information inputs (much like the 132 computers on a stealth fighter plane) to keep the body “on course” and stable.  Imbalances in this neuromatrix are also capable of producing self-destructive situations of which RCPD is but one example.

Pain Systems

As animals development continued through the eons their nervous systems kept pace.  The human nervous system, the most advanced on this planet, is the proud possessor of two basic systems whose understanding in helpful in understanding the use of neurostimulation for the treatment of pain.

PaleoSpinalthalamic System

This is the old (paleo) pain transmitting system seen in lower animals.  It is not very refined or sophisticated and is thus not very point specific.  The perception of pain transmitted by this system is that of a constant low grade aching which is diffuse in nature.

NeoSpinalthalamic System

This is the more advanced (neo) pain transmitting pathway which is point specific and highly localizing.  The pain perception is that of sharp and intense pain which is well localized to the body part.

When an individual sustains a bone fracture the Neo component is the intense sharp well-localized pain.  The Paleo component is the dull aching discomfort which replaces the initial sharp pain.  The Paleo system is there to remind the animal to protect and not use the afflicted body part.  For reasons not well understood neurostimulation is more effective in relieving pain of the PaleoSpinalThalamic type.

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