What is Complex Regional Pain Syndrome?

Jul 27

Complex Regional Pain Syndrome (CRPS) refers to severe and prolonged pain and local inflammation following an injury to an arm or leg. It used to be called reflex sympathetic dystrophy (RSD) and causalgia [1]. People with CRPS have an exaggerated painful response, which can make to something as mild as light touch to the affected area become severely painful.

How Common is Complex Regional Pain Syndrome?

CRPS affects approximately 200,000 patients per year. CRPS affects women 3-4x more frequently than men. The peak age of onset is around 40 years old, but varies from 37-70 years of age. It tends to occur most frequently in people of European ancestry [5].

What are the Early Signs of Complex Regional Pain Syndrome?

Initial signs of CRPS are short episodes of severe, shooting or burning pain or “pins and needles” sensation across a singular region of the arm or leg. These may be spontaneous or provoked and quickly resolve or last for several minutes. Triggering events include lightly touching the area, a wind or cold breeze hitting the skin, or clothing rubbing against the involved area.

Other symptoms that may be present alongside fluctuating pain include:

excess or prolonged pain after use or contact
Changes in the temperature, color, or swelling of the affected limb
Changes in the texture of the skin
Abnormal sweating of the area
Abnormal hair and nail growth of the limb
Stiffness of affected joints
Wasting away of bone or excess bone growth
Impaired muscle strength and movement

What are the Later Symptoms of Complex Regional Pain Syndrome?

Later symptoms of CRPS include longer episodes or more frequent episodes in the CRPS affected distribution. Chronic CRPS lasts for longer than 6 months. In most cases, CRPS improves over time, but in some rare cases it becomes severe and debilitating. Outcome of CRPS is highly variable and depends greatly on multiple factors including general health of the person and their nervous system, age, circulation, nutrition, smoking, diabetes, and chemotherapy [1].

What Causes Complex Regional Pain Syndrome?

In more than 90% of CRPS cases, the cause is a history of prior injury to the affected area, such as fractures, surgery, sprains/strains, burns or cuts, limb immobilization (from casting) or rare penetrations of the skin like from a cut or needle stick [1]. Often poor circulation can impede nerve and tissue healing, as well as conditions like diabetes or exposure to nerve toxins which can leave the nerves vulnerable. This leads to poor nerve recovery and increased excitability of the nerves that carry pain signals to the brain.

What Happens in the Brain with Complex Regional Pain Syndrome?

CRPS is most commonly caused by improper function of peripheral C-fiber nerve fibers that carry pain signals know as nociception to the brain. Increased firing of these fibers also triggers the type of inflammatory response designed to heal injuries.

It is important to understand that pain is not a sensation; pain is a perception and an experience. People tend to think of their pain system as a series of on-off switches, in that if they are not experiencing pain, their pain system must be shut off. Nothing can be further from the truth.

There are receptors called nociceptors that exist throughout your body. These receptors respond to heat, cold, chemical irritants, and mechanical compression. When these are stimulated, they come to threshold and fire nociceptive signals through small nerve fibers and into your spinal cord. These nociceptive neurons are just like any other neurons in your body; they are always firing at a baseline rate. Indeed, essentially only nociceptive neurons that are not firing at all times are the dead ones. So why are we not in 24/7, head to toe pain?

There are also several anti-nociceptive mechanisms in your nervous system, which exist in your spinal cord and brainstem. They function to filter and gate the nociceptive input, which prevents the signal from making it to the conscious parts of your brain. With enough input from the nociceptive systems, such as when there is tissue damage or inflammation, the anti-nociceptive systems are overwhelmed, and the signal is transmitted to areas in the parietal lobe of the brain where we map the body. Even once this occurs, we still don’t have pain, only localized nociception. The input doesn’t become pain until we assign a negative emotional valence to it; we must decide “that sucks” for the signal to become a painful experience.

The brain’s anti-nociceptive circuits are normally very good at shutting off incoming nociception before it reaches conscious experience. These systems exist in the frontal and prefrontal cortex, the parietal lobe, the vestibular system, the brainstem, and the spinal cord. When functioning properly, the nociceptive input from an injury is maintained long enough to allow it to function as part of the healing process. Nociception allows us to automatically regulate blood flow and focus inflammation on injured tissues, which is crucial for tissue repair. Once this takes place, nociception needs to be shut back off.

The literature demonstrates frontal and prefrontal cortex impairment specific to CRPS [4]. The brain becomes very efficient at perceiving pain, but the areas necessary to shut it back off are dysfunctional in CRPS.

There are also regions in the brain that are involved in the negative experience of pain. The amygdala is involved in threat detection and fear perception. The hypothalamus and pituitary gland are involved in the release of stress hormones that allow us to respond to threats. Some of these hormones can sensitize nociceptors, and thus make anything that hurts hurt more. The anterior cingulate cortex is involved in the perception of suffering. When this is excited, nociceptive input becomes a negative, painful experience.

Chronic pain is best seen as a loss of balance between the nociceptive and anti-nociceptive systems, coupled with a negative emotional consequence leading to ongoing painful experience. In acute pain, nociception tells your brain that tissue has been injured. In chronic pain, these signals persist and become amplified. They may even continue to exist long after the tissue has healed and returned essentially to normal.

When our bodies are stimulated by external sensations such as stubbing your toe or burning your hand, the sensory receptors in our skin relay that signal to the spinal cord. These signal travel in a pathway that delivers the message from the spinal cord to the brain. Under normal circumstances, this input is recognized as not very harmful, and no extreme signals of pain are ascribed to it. The body and brain sense and localize the external stimulus, deal with it by triggering inflammatory responses to heal the injured tissue, and move on.

In chronic pain, these pathways can produce an amplified response to the stimuli. The pain from the burn weeks ago maybe continue to be painful due to a process in the brain called central sensitization. An imbalance between the nociceptive and anti-nociceptive systems can lead to failure to properly shut off the nociceptive input once the tissue heals. This allows the nociceptive neurons to keep firing, become more sensitive, and more efficient. When these nerve cells wind up, they can become so sensitive and efficient that normal sensory input from light touch or gentle pressure, and the normal chemical environment can all become triggers. With enough central sensitization, just about any normal sensation can become painful [9].

Central pain states also involve changes in the areas of the brain where pain is perceived. Chronic pain leads to changes in sensory maps of the body, such that the brain’s ability to localize a sensory input to a body part can become impaired. As the brain’s map of the affected area is reorganized by the nociceptive signals, it loses the ability to properly regulate the anti-nociceptive system. In essence, when this somatotopic reorganization takes place, the brain loses the ability to properly localize the affected body part. And if the brain does not know where a body part is in space, it cannot properly send it signals to shut off the incoming pain [10].

Areas in the brain involved in negative sensory experiences also undergo changes in chronic pain. The anterior cingulate cortex, the area where we experience suffering, has been shown to become extremely sensitized in chronic pain states [9]. Most chronic pain patients note that they experience negative emotions at higher levels than before their injuries, their ability to regulate negative thoughts and negative self-talk is decreased. This is largely due to the excessive wind up of the anterior cingulate cortex seen in chronic pain. As a result, depression and anxiety are extremely common in cases of chronic pain [11].

The presence of these disorders leads to changes in stress systems, including upregulation of the hypothalamic-pituitary adrenal axis. The increase in circulating stress hormones can lead to further promotion of chronic pain [12]. These changes also promote neuroinflammation, which is inflammation taking place within the spinal cord and brain, leading to further loss of the ability to shut off the experience of pain [13].

The ultimate consequence of all of these processes is that central pain responses can become exaggerated and long lasting. Worse, the perception of pain can become decoupled from the sensation of tissue damage, and the perception of pain can exist long after the tissue has fully healed, or exist in response to normal background stimulation. Worse still, the emotional changes seen with chronic pain can spill over into all domains of a person’s lived experience, creating the changes in mood, motivation, and cognition seen in chronic depression and anxiety [9].

Patients regularly struggle to find successful treatments for their chronic pain, bouncing from provider to provider chasing progressively more invasive structural interventions without success. This is usually because both the patients and their providers fail to understand that their pain is no longer about what is occurring in the tissue, but rather is about circumstances in the brain that must be addressed for their pain to improve.

How is Complex Regional Pain Syndrome Diagnosed?

CRPS is diagnosed with a complete medical history and physical exam that can direct attention to any serious conditions that may be underlying and causing secondary trigeminal neuralgia. A neurological exam should also be performed to determine cause and create a treatment plan. Having a patient draw the outline of their most abnormal skin region is helpful in diagnosing the nerve affected. Other tests may be performed [1]:

nerve conduction studies, these may detect some but not all CRPS-associated nerve injuries
Imaging of the nerves by ultrasound or MRI can sometimes reveal nerve damage, as well as affected bone and bone marrow abnormalities which may help in diagnosing the affected nerve
Triple-phase bone scans that use dye sometimes show CRPS-associated excess bone resorption to help in diagnosis and localization of the primary issue

How is Complex Regional Pain Syndrome Usually Treated?

Initial treatment diagnosis of CRPS is very important, as the literature demonstrates the brain changes drastically between acute and chronic forms of CRPS [6]. The treatments that patients often engage in are [1]:

physical therapy and rehabilitation, which is a critical treatment for CRPS. By maintaining motion of the joints and muscles affected in CRPS, blood flow to the region improves and the nerve(s) damaged can begin to heal. It will also mitigate secondary neurodegeneration of the spinal cord and brain that accompany disuse of limbs over time [2]
Occupational therapy, to help people learn new ways to become active and return to work or activities of daily living
Psychotherapy, become people with severe CRPS often develop secondary psychological issues including depression, situational anxiety, fear-avoidance behavior and post-traumatic stress disorder. These all increase pain perception and further reduce activity and neurological function making it challenging for people to engage in therapies that will help them improve.
Medication to decrease pain and associated inflammation, either orally or topically
Spinal cord stimulation
Sympathetic nerve block, used less frequently now because long term efficacy has not been shown, but the goal was to decrease activity of sympathetic nerves and improve blood flow
Alternative treatments, such as behavior modification, medical marijuana, acupuncture, relaxation techniques can be useful for the individual but often do not diminish the pain itself.

How Is the NeuroRescue Program Different?

We may be able to significantly reduce or resolve Complex Regional Pain Syndrome by employing a host of advanced therapies and technologies that can help improve the function of your remaining systems. By doing so, we can often help restore appropriate nociceptive modulation from the affected area.

Much of what happens in CRPS is related to inappropriate firing of anti-nociceptive receptors to diminish how much nociceptive information is being transmitted to the brain. These receptor systems exist in the frontal and prefrontal cortex, the parietal lobe, the vestibular system, the brainstem, and the spinal cord.

In order for you to move through and interact with the world, you first need to know where the world is. Saccades are fast eye movements that shift gaze between targets. Vestibulo-ocular reflexes are reflexes that allow us to turn our head while maintaining gaze on a fixed target. Saccades need to be fast, accurate, stable, and have very quick reaction times. VORs need to be precise and have equal amounts of head and eye movement. As the frontal and prefrontal cortex, parietal lobe, vestibular system and brainstem are involved in both of these functions, the literature demonstrates that breakdown of these important reflexes occurs in patients with CRPS. We find that by rehabilitating saccades and VORs in a very precise manner, we can often improve function to each of these neurological regions, as well as improve function of the nervous system to support our anti-nociceptive receptor systems.

There are a host of other therapies that we engage in with our Complex Regional Pain Syndrome patients. All of these have different functions and allow us to rehabilitate specific capacities. These range from vestibular rehabilitation, as noted above, to using therapies such as mirroring to remap somatosensory maps of the affected limb [14, 15]. They include a number of different types of electrical stimulation to improve cognition, eye movements, and pain inhibition [7]. They even include therapies such as transcranial magnetic stimulation (TMS) to improve anxiety and depression surrounding the disorder [8], and cold laser therapy [3] directly to the area of nerve damage to improve circulation locally.

No two Complex Regional Pain Syndrome presentations are alike, and the same holds true for the NeuroRescue program. A cookie-cutter approach will be doomed to fail in a condition as complicated as Complex Regional Pain Syndrome. All of our therapy protocols are tailored to the unique needs of the individual.

How does the NeuroRescue Program work?

We design your unique NeuroRescue Program to be among the most comprehensive diagnostic and therapeutic protocols available today. We create individual NeuroRescue Programs based on a comprehensive analysis of every relevant neurological system and pathway, using gold-standard, cutting edge neurodiagnostic technologies and examination procedures and state-of-the-art therapies.

We begin with your Discovery Day, wherein we perform a comprehensive history of not only your condition, but your life on a timeline. This allows us to dive deeply into your case and see all of the factors that led to where you are now. It helps us uncover hidden problems and associated conditions that may be making it difficult for you to move your recovery forward.

In the case of Complex Regional Pain Syndrome, this requires a deep dive into the gut microbiome, intestinal wall permeability, circulation, nutrition, smoking, history of insulin resistance or diabetes, and past medical history including chemotherapy or other diseases or disorders that may have compromised circulation.

Our examination allows us to identify the areas and pathways of your brain that have been impacted to cause your Complex Regional Pain Syndrome. We begin by precisely quantifying the function of your visual, vestibular, and proprioceptive systems through computerized analysis of your eye movements, your inner ear reflexes, and your balance in a host of different sensory conditions.

We employ technologies including Videooculography and Saccadometry to measure several classes of eye movements. We use Video Head Impulse Testing to measure the function of your inner ear, and Computerized Dynamic Posturography to assess your balance in different sensory conditions.

We use NeuroSensoryMotor Integration testing to evaluate hand-eye coordination and cognition, and Virtualis testing to assess dynamic eye tracking and perception of vertical in a virtual reality environment.

We combine all of this with a comprehensive physical and neurological examination of your sensory, motor, autonomic, and cognitive systems. We review any relevant laboratory testing, radiological imaging, and prior neurodiagnostic testing, and integrate that information with our findings.

We use this information to identify which parts of your brain are working properly, which systems are struggling, and the precise point at which your systems fatigue.

We can then design a NeuroRescue Program that is unique and specific to your brain, and yours alone. Your NeuroRescue Program works to rejuvenate and reintegrate the damaged neurons and pathways in your brain. It works to improve energy, endurance, and functional capacity within your fragile systems.

We use our technologies and procedures to not only see what we need to address, but also when it is time to stop and let you rest. We address your impaired neurological function from multiple angles of therapy, and provide metabolic support to improve neurological recovery.

Your NeuroRescue Program allows us to take the pathways that are inefficient and maximize their efficiency and endurance. And by focusing on the integration of systems, we can do more than just get pathways working better, we can get them working together again. This gives us our best opportunity to help you live a healthy, vibrant, and fulfilling life.

Your Next Best Step:

Living with Complex Regional Pain Syndrome is challenging and debilitating. We have successfully resolved many cases of CRPS with the NeuroRescue Program. This is a challenging condition to treat, and no one can guarantee a full resolution of CRPS symptoms. While we may not always be able to cure your condition, with proper and comprehensive therapy many of the symptoms can become manageable, function can be enhanced, and quality can often be significantly improved.

To see if the NeuroRescue Program is right for you, contact one of our patient care coordinators to schedule your Discovery Day.

And remember, it’s never too late to start getting better.