Central sensitization is a phenomenon that occurs in the dorsal horn, which can be best described via 4 different states:
1) Normal: Inputs = outputs; innocuous sensations are perceived as such.
2) Suppressed: Inputs that would hurt do not; think an athlete who injures himself but finishes the game.
3) Increased sensitivity: Pain system has lower activation threshold, leading to pain spreading and pain with light touch and gentle movement. This change occurs because A beta fibers begin taking over C fiber locations in the dorsal horn.
4) Maintained afferent barrage, CNS influences, and morphological changes: Long lasting changes in the dorsal horn from a persistent driver, such as…
A fiber phenotype changes.
Persistent DRG discharge.
Gene transcription change in dorsal horn neurons.
Inflamed dorsal horn or DRG
Maladaptive beliefs, fears, and attitudes.
Dorsal horn sprouting; A Beta fibers take over C fiber space.
Persistent glutamate activity.
The CNS has an endogenous pain control system which activates during injury threat, noxious cutaneous input, or expectations and learning. Such an example of this is when you go to a healthcare practitioner’s office and no longer hurt. Another example of when this system is activated is during aggressive manual therapy. Think about how good your body may feel after sustained pressure or even a needle to a trigger point.
Central Sensitization Patterns
Symptoms not in neat anatomical/dermatomal boundaries.
Original pain spreads.
Multiple areas: Either linked or get one pain, then the other.
Contralateral side may be painful, though not like the other side (mirror pain).
Clinicians end up chasing pain.
Sudden, unexpected stabs.
Patients call the pain “It.” For example, “It has a mind of its own.”
Ongoing pain perception past normal healing times.
Summation via repetitive activities (sitting at a computer).
Distorted stimulus/response relationship. May get pain 10 seconds or days after stimulus is applied.
Unpredictable response to treatment/input, but ends up being predictable (x may only work 2 days).
Every movement hurts, but not big ROM loss (Symptom instability).
“It hurts when I think about it.”
Can be cyclical.
Change in other systems.
Links to traumatic life events.
Miracle cures can work.
Likely in most syndromes (fibromyalgia, complex regional pain syndrome).
2) Do not focus on finding an anatomical pain source which can make matters worse.
3) False positive are frequent on testing when tissues may be healthy (Eg, positive straight leg raise may just be adding slightly noxious input that results in an increased afferent barrage).
4) The physical exam is best considered a sensitivity test.
Increased levels of norepinephrine (physical stress), epinephrine (mental stress), and cortisol (shut down nonessential systems to maintain homeostasis) are upregulated and contribute to, but do not cause, pain. High sympathetic states can lead to problems that include tissue degeneration, mood swings, slow tissue healing, and increased infection susceptibility in people with chronic pain. Tissue change is particularly evident because the sympathetic nervous system innervates and interacts with muscles, joints, skin, connective tissue, inflammatory chemicals, AIGS, and the DRG. The parasympathetic nervous system is also important to mention to our patients in terms of healing effects of sleep and relaxation.
When we discuss peripheral issues, we are not only talking about the pathoanatomical source, but pathobiological processes dominating the clinical picture. There are several instances in which the pathoanatomical model falls short:
Tissues do get injured, but we must not forget the nervous system’s intricate link to injury. When tissues are hurt, they repair but are unlikely to ever be the same again. To protect against further threat, the CNS has the ability to increase nerve sensitivity. This change happens only if the person decides consciously or subconsciously that there is a need for it, and does not occur in everyone. There are two ways in which this sensitivity develops;
Primary sensitivity: Increased sensitivity to input at the injury site.
Secondary sensitivity: Increased sensitivity to uninjured tissues around the injury.
All pain is neurogenic, operates in a continuum, and has many components.
NOC is tissue pain that occurs at a neuron’s end that is excited by mechanical, thermal, or chemical stimuli. It does not always match up with tissue health status. A normal nerve ending has a very high firing threshold, and nearly 1/3 will never fire. These are called silent nociceptors.
Looking at a chemical process such as inflammation shows us how these nerves fire. When acute inflammation begins, a chemical soup with a swelling broth enters the area. Inflammatory chemicals flood the area, lowering the nerve’s firing threshold and increasing its firing rate. This process makes movements painful. In a chronic inflammatory case, the body becomes depleted of inflammatory mediators, thus potentially leading to change in the sensory neuron’s properties.
The nervous system is also involved with inflammation. C fibers begin neurogenic inflammation by releasing substance P and CGRP. These chemicals flatten capillaries, which further encourage swelling. The spinal cord uses antidromic impulses (firing in an opposite direction along a nerve) to mediate inflammation, thus suggesting a central influence.
The sympathetic nervous system can affect inflammation by releasing catecholamines, which maintain or enhance pain. This gives us clinicians a way to affect the inflammatory response by targeting stress reduction.
There are two ways to classify NOC based on inflammatory response. It is much easier to do this than it is to find a structure at fault.
Fluids forced out of tissues.
Evident in prolonged/unusual postures
End of the day
Rapid ease with posture change
Poor anti-inflammatory response
Acute pain / tissue damage
Concordant signs (redness, swelling, temperature change, etc.)
Hints of an unhealthy nervous system
Peripheral Neuropathic Pain (PNP)
Butler lists several modern concepts of nerves.
1) Peripheral nerves are long, living, and responsive tissues.
2) The dorsal root ganglion is the peripheral nervous system’s brain.
3) Nerves are stable and take many mechanical forces during movement
4) Axons are highways that transmit pulses, which get modified but abnormal impulse generating sites (AIGS) in chronic pain.
5) A nerve’s connective tissue is innervated and capable of causing pain. Therefore healthy connective tissue = healthier nerve.
6) It is unlikely that nerve entrapment exists on its own. Stress response and central sensitization likely occur as well.
7) The immune system plays a role in PNP.
When a peripheral nerve segment becomes injured, it can begin to generate its own impulses. These sites can form just about anywhere in the nervous system, including the spinal cord and dorsal root ganglion. AIGS can only occur in sensory nerves, and are likely what neurodynamic tests affect. Here is a list of stimuli that can cause an AIGS to fire.
6) Spontaneously: You’ll notice this when people cannot give an aggravating activity or likely an innocuous unperceived incident.
7) Mechanical: if nerves do not slide or glide well, more force is placed on the AIGS. Moreover, scar tissue formation highly correlates with nerve root mechanosensitivity.
One very important point to make, and this goes for all injuries is that pain does not equal injury. There have been several cadaveric studies that demonstrate nerve damage or compression in people who never complained of pain.
– Dermatomal or cutaneous innervation field. Can be a localized part.
– Pain along a nerve trunk.
– Minor spot pain (trigger point – an AIG in a cutaneous nerve struggling with relationship to myofascia).
– Motor involvement.
– Burning, especially in cutaneous nerves.
– Diffuse cramping if it is a nerve that innervates muscle.
– Paresthesia in a peripheral neural zone.
– Evoked by nerve movement or surrounding tissue change.
– Mechanosensitivity beginning, during, or at stimulus release.
– DRG – More spontaneous.
– Linked to stressed states or inflammation.
– Antalgic postures.
– AIGS give weird symptoms like strings pulling, ants, and/or electrical feelings.
– AIGS may be silent for a few days after injury.
Ultimately, the goals of treating these conditions follow a 3 step approach with the overall goal being turning a firing nerve off.
1) Alter sympathetic and immune inputs – explain pain, make goals, and decrease fear.
2) Increase circulation – simple exercise
3) Decrease mechanical forces – posture, nervous system health, and altering temperature.
This treatment must be done as soon as possible, for if AIGS continue to fire, the CNS may upregulate and lead to central sensitization.
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.
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.
Wetware includes the different neurotransmitters and neuromodulators. Examples include the following:
GABA – Inhibitor
Glutamate – excitor (2 types)
NMDA – Important in memory acquisition and long term sensitivity changes.
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:
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.
For example, injury states lead dramatic changes in receptor numbers in various brain locations.
Peripheral nerves usually don’t have ion channels unless demyelination occurs, which can lead to a high channel density at the damaged site.
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.
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.
This book is an all-encompassing manual regarding neurodynamics. This concept is defined as the physical and related physiological abilities of the nervous system.
Before delving into neurodynamic nitty-gritty, a brief history of physical therapy is laid out via a very cool brachial plexus design (you have to get the book to see it). There are three different progressions in physical therapy history: manual therapy, exercise, and neurological manual therapy.
The first time PTs learned manipulation was in 1916 at St. Thomas Hospital in London. The thought process of the time, as well as most early manual therapy, was predominantly biomechanically joint-centric. Eventually, muscle and other tissues were targeted. These approaches were championed by Geoffrey Maitland’s signs and symptoms approach and Graves’ pathological model.
Concomitant with manual therapy has been exercise, which had moved from nonspecific (aerobics, tai chi) to specific movements a la Vladimir Janda and Shirley Sahrmann.
On the other side of orthopedic manual therapy were manual techniques from the likes of Bobath’s NDT and PNF. What is sad about these techniques is that they have not interacted much during manual therapy’s development. Butler makes arguably one of the most important statements in the book by saying our patients are ultimately all neurological. We will all meet at the brain.
Aside from various manual approaches, recent techniques have been developed including psychology, counseling, exercise physiology, and acupuncture. Butler feels these are nice adjuncts to the plan of care.
The key manual therapy points Butler wishes to make are as follows.
1) Manual therapy is young, slightly over 2 generations.
2) In this short time frame, rapid change has occurred.
3) Relies heavily on tissue, usually muscle or joint.
Neurodynamics is not a new approach. Tension tests were mentioned as early as 1929. Butler argues that all the tissue techniques that manual therapy advocates have unconsciously encouraged the nervous system to move.