Complex Regional Pain Syndrome most frequently occurs following and injury but can also occur from long standing pain problems leading to central sensitization. CRPS is one of the most difficult disorders to treat. Prior to discussing Sphenopalatine Ganglion Blocks in the treatment of CRPS it is important to understand the basics.
Patients with CRPS often experience Hyperalgesia or increased sensitivity to nociceptive input can be severe with even minimal noxious stimulation leading to severe or paroxysmal pain responses and Allodynia, the perception of pain from non-nociceptive input such as light touch.
Complex Regional Pain Syndrome is the current designation for what was previously called reflex sympathetic dystrophy (RSD) and /or causalgia
Another designation was reflex neurovascular dystrophy (RND) which is an amplified musculoskeletal pain syndrome (AMPS).
CRPS frequently is associated with systemic autonomic dysregulation with major effects on the CNS or Central Nervous System and resultant symptoms including neurogenic edema.
The International Association for the Study of Pain describes two types of CRPS: Type I previously designated as reflex sympathetic dystrophy (RSD) and Type 2 previously designated as Causalgia.
Type one is also referred to as Sludeck’s Atrophy, Reflex Neurovascular Dystrophy or Algoneurodystrophy. Type 1 is by far the most common type of CRPS . Nerve lesions have not yet been confirmed in type 1 CRPS.
Type 2 by contrast routinely has easily seen nerve damage which may be why it is more difficult to control. While Type 1 is often considered Idiopathic disease Type 2 has a presumed cause of obvious frank nerve damage.
Treatment is challenging in cases of CRPS and is often unsatisfactory especially after the condition has become advanced. The enormous degree of enhanced sympathetic activity causing secondary vasoconstrictionmake some believe there is an unidentified neurotransmitter involved.
My personal theory is a combination of Neural Plasticity causing severe Central Sensitization with increased afferent nociceptive sensitivity leading to storms of neurotransmitter release inside the brain and possible wide spread chages in Gap Junctions in the CNS which could explain the spread of CRPS in affected individuals. The communication could spread directly cell to cell and not synaptically. The Glial cells could be a likely suspect of transmitting this gap junction spread as would the Schwann Cells responsible for Myelin Sheath coverage of neurons.
Secondarily, there is a descending storm of efferent activity again leading to storms of neurotransmitter release as well as kinins and histamine that also may open up increased Gap Juntion spread of the disorder periferrally. The Afferent – Efferent spread will create an I/O error or input output error to the brain.. Computer experts would dub this
Garbage in – Garbage out.
In computers the tech would shut down the computer and reboot. In humans this is a more difficult problem. Ketamine has been used to treat CRPS but probably is most effective if used to prevent or reverse early CRPS. Ketamine is effective in reducing opiod use post-surgery. Opiod use stimultes the Glial cell to break down opiods therefore decreaing the amount used to control pain is key. Ketamine used to treat intractable neuropathic pain and is useful in preventing spinal sensitization, the wind-up associated with chronic pain. By reducing neuroplasticity it may prevent development of CRPS and other disorders associated with Central Sensitization.
While this may help with pain it will not be an effective “reboot” of the system. (below source wikipedia) The effect of Ketamine causes dissociation between the limbic and thalamoneocortical systems with intact ocular, laryngeal, and pharyngeal reflexes. Ketamine is an antagonist of the glutaminergic N-methyl-D-aspartate receptor (NMDA-R), both centrally and in the spinal cord, prevents neuronal Ca2+influx, interference with neuronal plasticity, learning and memory, analgesia at central and spinal cord level, as well as interruption of the central sensitization core to chronic pain syndromes.
Ketamine could be used early to prevent Central Sensization but it has weak evidence in the literature.
Pain Med 2015 Jan 13. doi: 10.1111/pme.12675. A systematic Review of Ketamine for Complex Rgional Pain Syndrome was a Cockchrane review that” yielded 262 articles, 45 of which met the inclusion/exclusion criteria. Of those included, 6 were reviews, 5 were randomized placebo-controlled trials, 13 were observational studies, and 21 were case reports.” The conclusions were “there is no high quality evidence available evaluating the efficacy of ketamine for CRPS and all manuscripts examined in this review were of moderate to low quality. Therefore, we conclude there is currently only weak evidence supporting the efficacy of ketamine for CRPS, yet there is clearly a rationale for definitive study.”
This does not mean Ketamine is not effective in individual cases, it just cannot yet be considred a first line treatment. I believe the reason Ketamine is only weak in response is that Ketamine doses are insufficient to reboot the system in both dosage and time of infusion.
The use of a Curare type anaesthesia is association with Ketamine may be the Reboot Mechanism that is necessary for severe CRPS. Theis will reversibly inhibit the nicotinic acetylcholine receptor at the physiologic junction. Curare was shown to effectively treat tetanus and strichnine poisoning by interfering with nerve conduction from motor neuron to muscle at the physiologic junction (think Botox). This would require total life support including respiration. While the patient is in the anaesthesized state Insulin Potentiation Therapy using a shocking dose of insulin could simultaneously be used to Reboot the system. Hyperbaric Oxygen Therapy is currently under investigation for CRPS therapy and conceivably could be used in conjunction with Insulin Potentiation. Insulin potentiation can also be used to move medications across cell membranes and /or the blood brain barrier. This could allow targeted medication use to limit adverse side effects of the medications. I first learned about Insulin Potentiation Therapy from a friend Dr Steve G Ayre a Canadian physician who worked with moving AZT across the Blood Brain Barrier in earl aids research. I learned fro Steve about Insulin Potentiation and then used the addition of very small amounts of insulin to lidocine while doing trigger point injections. Steve was conviced that Oxygen Potentiation held enormous benefits in the future.
Insulin Potentiation may become a treatment of choice for administering drugs to treat acquired Gap Junction Disease.
Cochrane reviews would never find evidence for drastic treatment of this type but considering the decrease in quality of life (QOL) in CRPS patients. A study “Risk factors for suicidal ideation among patients with complex regional pain syndrome.” by Lee DH, Noh EC, Kim YC, et al. in Psychiatry investigation. 2014 Jan;11(1):32-8. reported 74% of patients were considered at high risk for suicide. (abstract below).
The severe nature of CRPS and effects on QOL or Quality of Life demands seeking answers for our patients. Sympathetic Blocks including stellate ganglion blocks have had some success but there is little wrtten on the utilization of Sphenopalatine Ganglion Blocks for treating CRPS. ”
I recently had a patient in my office for routine dental work but due to her severe CRPS we had anaesthesia with Ketamine to facilitate what otherwise would have been incredibly painful experience. After the necessary dental work was done a bilateral SPG block was performed thru the greater palatine foramen intra-orally. The patients husband the pain relief from the Ketamine infusion lasted longer than when she goes in for just Ketamine infusion. These changes could be due to dosage and time of infusion or to addition of Parasympathetic Ganglion Block of the Sphenopalatine Ganglion.
I first began utilizing SPG Blocks in the 1980’s when a TMJ/ Headache/ Migraine patient brought in the book “Miracles on Park Avenue” about an ENT physician who treated all matters of pain with Sphenopalatine Ganglion Blocks. The patient wanted me to help them find a doctor who would perform the block. There were no doctors in greater Chicagoland area but a friend and mentor Dr Jack Haden in Kansas City taught me a simple method of doing SPG blocks transnasally. The effect was life changing for my patient and I have been an advocate ever since. There are numerous protocols for administering SPG Blocks including intra-oral and extra-cranial injections and transnasal approaches such as MiRx protocol with TX360 or use of Sphenocath. I prefer the original method I learned for Jack Haden and the book “Miracles on Park Ave: Treatment of Arthritis andd other Chronic Pain” by Albert Benjamin Gerber. The bibliography ain that book was my library index of articles I read to understand the SPG block.
The advantage to the original approach is that it can easily and safely be self administered by patients at home one or multiple times daily and is extremely effective in eliminating and/or preventing pain in many patients. It is a tool I use in treating TMD (TMJ) patients, Migraine , Chronic Migraine, Autonomic Cephalgia, Tension headache and Chronic Daily Headache patients.
Correcting underlying physiology is easier when patients are comfortable.
“Risk factors for suicidal ideation among patients with complex regional pain syndrome.” Lee DH, Noh EC, Kim YC, et al. Psychiatry investigation. 2014 Jan;11(1):32-8.
Objective: Chronic pain frequently coexists with psychiatric symptoms in patients diagnosed with complex regional pain syndrome (CRPS). Previous studies have shown a relationship between CRPS and the risk of suicide. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS.
Methods: Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD), and symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I, SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI).
Results: Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p=0.002), severity of pain (p=0.024), and low scores on the GAF (p=0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep.
Conclusion: Significant risk factors for suicidal ideation in patients with CRPS include severity of pain, depressive symptoms, and decreased functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.
***What follows is Reprinted from the National Institute of Neurological Disorders and Stroke*****
What is complex regional pain syndrome?
Complex regional pain syndrome (CRPS) is a chronic pain condition most often affecting one of the limbs (arms, legs, hands, or feet), usually after an injury or trauma to that limb. CRPS is believed to be caused by damage to, or malfunction of, the peripheral and central nervous systems. The central nervous system is composed of the brain and spinal cord, and the peripheral nervous system involves nerve signaling from the brain and spinal cord to the rest of the body. CRPS is characterized by prolonged or excessive pain and mild or dramatic changes in skin color, temperature, and/or swelling in the affected area.
There are two similar forms, called CRPS-I and CRPS-II, with the same symptoms and treatments. CRPS-II (previously called causalgia) is the term used for patients with confirmed nerve injuries. Individuals without confirmed nerve injury are classified as having CRPS-I (previously called reflex sympathetic dystrophy syndrome). Some research has identified evidence of nerve injury in CRPS-I, so the validity of the two different forms is being investigated.
CRPS symptoms vary in severity and duration. Studies of the incidence and prevalence of the disease show that most cases are mild and individuals recover gradually with time. In more severe cases, individuals may not recover and may have long-term disability.
Who can get CRPS?
Anyone can get CRPS. It can strike at any age and affects both men and women, although it is much more common in women. The average age of affected individuals is about age 40. CRPS is rare in the elderly. Children do not get it before age 5 and only very rarely before age 10, but it is not uncommon in teenagers.
What are the symptoms of CRPS?
The key symptom is prolonged pain that may be constant and, in some people, extremely uncomfortable or severe. The pain may feel like a burning or “pins and needles” sensation, or as if someone is squeezing the affected limb. The pain may spread to include the entire arm or leg, even though the precipitating injury might have been only to a finger or toe. Pain can sometimes even travel to the opposite extremity. There is often increased sensitivity in the affected area, such that even light touch or contact is painful (called allodynia).
People with CRPS also experience constant or intermittent changes in temperature, skin color, and swelling of the affected limb. This is due to abnormal microcirculation caused by damage to the nerves controlling blood flow and temperature. An affected arm or leg may feel warmer or cooler compared to the opposite limb. The skin on the affected limb may change color, becoming blotchy, blue, purple, pale, or red.
Other common features of CRPS include:
- changes in skin texture on the affected area; it may appear shiny and thin
- abnormal sweating pattern in the affected area or surrounding areas
- changes in nail and hair growth patterns
- stiffness in affected joints
- problems coordinating muscle movement, with decreased ability to move the affected body part, and
- abnormal movement in the affected limb, most often fixed abnormal posture (called dystonia) but also tremors in or jerking of the affected limb.
What causes CRPS
Doctors aren’t sure what causes some individuals to develop CRPS while others with similar trauma do not. In more than 90 percent of cases, the condition is triggered by a clear history of trauma or injury. The most common triggers are fractures, sprains/strains, soft tissue injury (such as burns, cuts, or bruises), limb immobilization (such as being in a cast), or surgical or medical procedures (such as needlestick). CRPS represents an abnormal response that magnifies the effects of the injury. In this respect it is like an allergy. Some people respond excessively to a trigger that causes no problem for other people.
Peripheral nerve abnormalities found in individuals with CRPS usually involve the small unmyelinated and thinly myelinated nerve fibers (axons) that carry pain messages and signals to blood vessels. (Myelin is a mixture of proteins and fat-like substances that surround and insulate some nerve fibers.) Because small fibers in the nerves communicate with blood vessels, small nerve fiber injuries may trigger the many different symptoms of CRPS. Molecules secreted from the ends of hyperactive injured small nerve fibers are thought to contribute to inflammation and blood vessel abnormalities. These peripheral nerve abnormalities in turn trigger abnormal neurological function in the spinal cord and brain, leading in some cases to complex disorders of higher cortical function.
Another abnormality in CRPS involves the blood vessels in the affected limb, which may dilate (open wider) or leak fluid into the surrounding tissue, causing red, swollen skin. The underlying muscles and deeper tissues can become starved of oxygen and nutrients, causing muscle and joint pain and damage. At times, the blood vessels may over-constrict (clamp down), causing cold, white, or bluish skin. The dilation and constriction of small blood vessels is controlled by small nerve fiber axons as well as chemical messengers in the blood.
CRPS also affects the immune system. High levels of inflammatory chemicals (cytokines) have been found in the tissues of people with CRPS. These contribute to the redness, swelling, and warmth reported by many patients. CRPS is more common in individuals with other inflammatory and autoimmune conditions such as asthma.
Limited data suggest that CRPS also may be influenced by genetics. Rare family clusters of CRPS have been reported. Familial CRPS may be more severe with earlier onset, greater dystonia, and more than one limb being affected.
Occasionally CRPS develops without any known injury. There may have been an internal injury caused by an infection, a blood vessel problem, or entrapment of the nerves, so careful examination is needed to determine the cause and treat it.
In many cases, CRPS is the result of multiple causes that act together to produce various symptoms.
How is CRPS diagnosed?
Currently there is no single diagnostic test to confirm CRPS. Diagnosis is based on the affected individual’s medical history and signs and symptoms that match the definition. But because several other conditions can cause similar symptoms, careful examination is important. Since most people improve gradually over time, diagnosis may be more difficult later in the course of the disorder.
Testing also may be used to help rule out other conditions, such as arthritis syndromes, Lyme disease, generalized muscle diseases, a clotted vein, or small nerve fiber polyneuropathies (such as from diabetes), because these require different treatment. The distinguishing feature of CRPS is usually a history of earlier injury to the affected area, as most of these other conditions are not triggered by injury. Individuals without a history of injury should be carefully examined to make sure that another treatable diagnosis is not missed.
Magnetic resonance imaging or triple-phase bone scans sometimes identify CRPS-characteristic changes in the bone metabolism. CRPS is often associated with excess bone resorption, a process in which certain cells break down the bone and release calcium into the blood.
What is the prognosis?
The outcome of CRPS varies from person to person. Almost all children and teenagers have good recovery. Occasionally individuals are left with unremitting pain and crippling, irreversible changes despite treatment. Anecdotal evidence suggests early treatment, particularly rehabilitation, is helpful in limiting the disorder, but this benefit has not yet been proven in clinical studies. More research is needed to understand the causes of CRPS, how it progresses, and the role of early treatment.
How is CRPS treated?
The following therapies are often used:
Rehabilitation therapy. An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms. Additionally, exercise can help improve the affected limb’s flexibility, strength, and function. Rehabilitating the affected limb also can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Occupational therapy can help the individual learn new ways to work and perform daily tasks.
Psychotherapy. CRPS and other painful and disabling conditions often are associated with profound psychological symptoms for affected individuals and their families. People with CRPS may develop depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult. Treating these secondary conditions is important for helping people cope and recover from CRPS.
Medications. Several different classes of medication have been shown to be effective for CRPS, particularly when used early in the course of the disease. No drug is approved by the U.S. Food and Drug Administration specifically for CRPS. No single drug or combination of drugs is guaranteed to be effective in every person. Drugs to treat CRPS include:
- non-steroidal anti-inflammatory drugs to treat moderate pain, including over-the-counter aspirin, ibuprofen, and naproxin
- corticosteroids that treat inflammation/swelling and edema, such as prednisolone and methylprednisolone (used mostly in the early stages of CRPS)
- drugs initially developed to treat seizures or depression but now shown to be effective for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, nortriptyline, and duloxetine
- botulinum toxin injections
- opioids such as oxycontin, morphine, hydrocodone, fentanyl, and vicodin
- N-methyl-D-aspartate (NMDA) receptor antagonists such as dextromethorphan and ketamine
- nasal calcitonin, especially for deep bone pain, and
- topical local anesthetic creams and patches such as lidocaine.
All drugs or combination of drugs can have various side effects such as drowsiness, dizziness, increased heartbeat, and impaired memory. Inform a healthcare professional of any changes once drug therapy begins.
Sympathetic nerve block. Some individuals report temporary pain relief from sympathetic nerve blocks, but there is no published evidence of long-term benefit. Sympathetic blocks involve injecting an anesthetic next to the spine to directly block the activity of sympathetic nerves and improve blood flow.
Surgical sympathectomy. The use of this operation that destroys some of the nerves is controversial. Some experts think it is unwarranted and makes CRPS worse; others report a favorable outcome. Sympathectomy should be used only in individuals whose pain is dramatically relieved (although temporarily) by sympathetic nerve blocks. It also can reduce excess sweating.
Spinal cord stimulation. Placing stimulating electrodes through a needle into the spine near the spinal cord provides a tingling sensation in the painful area. Typically the electrode is placed temporarily for a few days to assess whether stimulation will be helpful. Minor surgery is required to implant all the parts under the skin on the torso. Once implanted, the stimulator can be turned on and off, and adjusted using an external controller. Data shows that about one-fourth of individuals develop equipment problems that may require additional surgeries.
Other types of neural stimulation. Neurostimulation can be delivered at other locations along the pain pathway, not only at the spinal cord. These include near injured nerves (peripheral nerve stimulators), outside the membranes of the brain (motor cortex stimulation with dural electrodes), and within the parts of the brain that control pain (deep brain stimulation). A recent option involves the use of magnetic currents applied externally to the brain (called repetitive Transcranial Magnetic Stimulation, or rTMS). The advantage is that no surgery is required; the disadvantage is need for repeated treatment sessions.
Intrathecal drug pumps. These devices pump pain-relieving medications directly into the fluid that bathes the spinal cord, typically opioids and local anesthetic agents such as clonidine and baclofen. The advantage is that pain-signaling targets in the spinal cord can be reached using doses far lower than those required for oral administration, which decreases side effects and increases drug effectiveness. There are no studies that show benefit specifically for CRPS.
Emerging treatments for CRPS include:
- Intravenous immunoglobulin (IVIG). Researchers in Great Britain reported that low-dose IVIG reduced pain intensity in a small trial of 13 patients with CRPS for 6 to 30 months who did not respond well to other treatments. Those who received IVIG had a greater decrease in pain scores than those receiving saline during the following 14 days after infusion. A larger study involving individuals with acute-phase CRPS is planned.
- Ketamine. Investigators are using low doses of ketamine—a strong anesthetic—given intravenously for several days to either reduce substantially or eliminate the chronic pain of CRPS. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments.
- Hyperbaric oxygen. Several studies have investigated the use of hyperbaric oxygen therapy for chronic pain. Individuals lie down in a tank containing pressurized air, which delivers more oxygen to the body’s organs and tissues. Although research is still experimental, some researchers report hyperbaric oxygen can reduce swelling and pain, and improve range of motion in individuals with CRPS.
Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment.
What research is currently being done on CRPS?
The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), is the primary Federal supporter of research on the brain and central nervous system. Other NIH institutes also support research on CRPS and other painful conditions.
NINDS-supported scientists are studying new approaches to treat CRPS and to intervene more aggressively to limit the symptoms and disability associated with the syndrome.
Previous research has shown that CRPS-related inflammation is supported by the body’s natural immune response. Researchers hope to better understand how CRPS develops by studying immune system activation and peripheral nerve signaling using an animal model of the disorder. The animal model was developed to mimic certain CRPS-like features following fracture or limb surgery, by activating certain molecules involved in the immune system process.
Limb trauma, such as a fracture and then having the limb placed in a cast, is a common cause of CRPS. By studying an animal model, researchers hope to better understand the neuroinflammatory basis of CRPS and to identify the relevant inflammatory signaling pathways that lead to the development of post-traumatic CRPS. They also will examine inflammatory effects of cast immobilization and exercise on the development of pain behaviors and CRPS symptoms.
Peripheral nerve injury and subsequent regeneration often lead to a variety of sensory deficits. Researchers hope to identify specific cellular and molecular changes in sensory neurons following peripheral nerve injury to better understand the processes that underlie neuroplasticity (the brain’s ability to reorganize or form new nerve connections and pathways following injury or death of nerve cells). Identifying these mechanisms could provide targets for new drug therapies that could improve recovery following regeneration.
Children and adolescents with CRPS generally have a better recovery than adults and offer a unique model for the study of chronic pain reversal. Scientists studying children with CRPS are investigating neuroplasticity and the biological processes that cause CRPS to occur, in the hopes of developing more effective therapies and accelerated recoveries for adults and children.