This is Chapter II summary of “The Sensitive Nervous System.”

Intro

Here we develop a framework for understanding the nervous system with pain as the centerpiece. The nervous system is very much misunderstood as an input/output system:

Myth: Input/output system.

Reality: The nervous system is an active activity constructor. It evolves and learns rather than computes. It is    also widely distributed without a master neuron pool for a particular sensation.

The nervous system is made up of two components, hardware and wetware.

The Hardware

Neurons make up the hardware. These components respond and keep a chemical history of many different inputs and outputs. This is true for each individual neuron, which allows each one to be ready to go when called upon. This hardware is one time when the part actual does equal the whole, as one neuron’s activity resembles the entire Central Nervous System’s (CNS) behavior.

The nervous system’s size is near-astronomical. There are approximately 100 billion neurons with 10¹⁴ synapses. This figure only factors in the functionally known nervous system components. If we throw in 10³ nodes/centers (connected by 10⁵ pathways) and the 10:1 glial cell:neuron ratio, and we have an incredibly dense system in place. A pinhead speck of brain tissue has 350 million connections.

This hardware is also very redundant, as very few neurons go straight from sensory organ to cortex.  There are several feedback loops in place which allows for constant checking and rechecking.

The Wetware

Wetware includes the different neurotransmitters and neuromodulators. Examples include the following:

• Amino acids
  • GABA – Inhibitor
  • Glycine
  • Glutamate – excitor (2 types)
    • NMDA – Important in memory acquisition and long term sensitivity changes.
    • AMPA
• Neuropeptides (2 types)
  • From hypothalamus – oxytocin and vasopressin
  • Opioids – Enkephalin, endorphins: affect pain perception.
• Acetylcholine – Works at the neuromuscular junction (NMJ); plays a key role in autonomic nervous system function.
• Amines – There are 2 categories.
  • Catecholamines: Run from brainstem to CNS. They function under autonomic and endocrine circuits. These upregulate in post-traumatic stress disorder (PTSD). There are 3 types:
    • Epinephrine
    • Norepinephrine
    • Dopamine
  • Serotonin: Inhibit sensory input. This chemical is often low in depressive disorders.

Even though neuron and brain behavior are mirrored, the same cannot be said between brain anatomy and chemistry. The wetware is very widespread and nonexclusive throughout the system. There are home bases for different components, but many brain areas are active when stimuli are applied.

Ion Channels 101

This brain activity is governed predominantly by ion channels. There are several types of ion channels, with the most common being…

• Voltage gated: Affected by electrical charge (milliseconds).
• Ligand/chemical gated: Affected by body chemicals (milliseconds).
• Mechanically gated: Affected by stretch/pressure (milliseconds).
• Metabolic-receptors: Slow-acting (several minutes) via G-proteins.

The longer an ion channel can stay open, the longer lasting change can occur. Therefore, targeting the G-proteins can lead to both large positive or negative consequences.

There are seven key points that Butler wishes to discuss regarding ions, which I have narrowed down to four:

1)      Ion channels are a collection of proteins that bind into neurons. Their lifecycle occurs as follows:

Synthesized on ribosomes → transported in the axoplasm→ Inserted into axolemma→ form a plug with a hole through it→ open/close via stimuli

2)      They are constantly changing and may only have a half-life of a few days. This allows for self-regulation.

3)      They are not distributed evenly, which allow for salutatory conduction.

4)      Ion channel number, kind, and activity at any one time represent the sensitivity needed for one’s survival.

1. For example, injury states lead dramatic changes in receptor numbers in various brain locations.
2. Peripheral nerves usually don’t have ion channels unless demyelination occurs, which can lead to a high channel density at the damaged site.

Action Potentials

Next we must talk about action potentials and their all-or-none firing capabilities. This quality can lead to continual spiking, which ultimately depend on the person’s needs and nervous system health status. At times such as in sport, this firing can be advantageous. But if a nerve is injured, it may repeatedly fire when less aggressive stimuli are applied.

Now, let us apply these concepts to the neuromatrix, which is the entire network whose spatial distribution and synapses are determined genetically and by sensory inputs. If we take pain as an example, there may be a certain genetic bias toward a particular pain state. Looking at the nurture aspect of this matrix, all experiences in which this pain occurs further sculpt what future pain is like.

Parallel and Bilateral Processing

Initially, information from the environment was thought to occur in a serial fashion. You prick your finger, which sends inputs all the way up to the brain.

   A→ B→ C→ D→E

However, more recent research has indicated that processing occurs in a parallel fashion, leading to great redundancies.

Parallel processing is why surgery for chronic pain usually fails. If we remove the D aspect of pain processing, B; C; and E will continue to get inputs from A.

Bilateral processing is also a recently discovered phenomenon, in which some neurons will react to stimuli from both sides of the body. This most often occurs in midline structures such as the trunk or mouth or with structures that work together such as the hands. This processing can also be seen with nociception, as ipsilateral nociception leads to bilateral brain activity.

The Brain and Movement

The cerebellum and basal ganglia are major players linking the brain and movement, as they facilitate motor program recall and movement-based thoughts. These areas are the movement planners. They play a role in motor imagery, as this modality has been shown to activate similar neural substrates as with motor performance.

The link between the brain and movement can by seeing how motor control and pain processing are related. It is fairly established that in the presence of pain, motor control is altered. Butler suggests that if motor control contributes to pain processing, then perhaps it can be disengaged from the pain experience.

Receptive fields and homunculi

Receptive fields are sensory surfaces which must be stimulated for a neuron to respond.  Generally these fields are connected from first to third order neurons in increasing complexity and fiber fashion.

These receptive fields are somatotopically arranged throughout the entire nervous system, meaning adjacent body parts a represented in adjacent sites. This arrangement anatomically facilitates plasticity, and may allow neighboring parts to take over during an injury.

This arrangement plays a large role in neuroplasticity, which is defined as neuron function change throughout the lifespan. For example, if a neuron were to go silent, the surrounding neurons would invade that space. This phenomenon can be seen in people who have had amputations, as oftentimes they can often feel their phantom limbs by touching an adjacent somatotopic area, such as the face. Another example would be with tinnitus, which Butler describes as an auditory phantom phenomenon. These representations can be altered by overuse, lack of use, minor injuries, and cognitive changes.

Neuroplasticity is not a fixed process, however. Representations can become smudged, in which pain in one area will often spread to adjacent areas. So the idea of shoulder pain on one side spreading to the other is not so farfetched. This is very often seen in people with chronic pain.

Clinical Repercussions

1)      Prior to any active or passive inputs, the nervous system must be primed prior by education; understanding; empathy; and skilled placebo.

2)      Altering one process could affect things on the whole

a.       E.g. resolving a workplace issue could affect tissue healing.

3)      Rest is harmful for spinal pain

4)      Normal movement ASAP.

a.       Present feared movements in different environments or segmented parts.

b.      Functional is desirable.

5)      The patient interaction may cue perception/reduction of pain depending on how you present yourself.

6)      Tissue-based therapy is useful in acute pain, but only a part of chronic pain management.

7)      Use it or lose it when discussing movement representations.

8)      A repeated or maladaptive movement will strengthen synapses, making the pattern difficult to change.

Useful Analogies

1)      The brain is like a garden. It needs to be watered and likes fertilizer (movement) now and then. You need to water all the parts, otherwise the over fertilized/watered parts will take over.

2)      Brain output is like cake. We combine several ingredients (inputs) and then that makes the output cake, at which point they cannot be separated.

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