Complex Regional Pain Syndrome following multiple knee surgeries and knee replacement

Ross A. Hauser, MD. 

Many people have very successful knee replacement surgeries. Some will suggest it was the “best thing they ever did.” Some people will not have this same outcome. They will have significant pain and they will not understand why they have more pain after the knee replacement than they did before the knee replacement. Worse for some is that their surgeon will suggest to them that according to the x-rays. Their knee replacement surgery was very successful. Here is an example of the type of story we may hear:

I had a total knee replacement less than two months ago. Through the recovery period, I suffered from extraordinary pain. My doctors and people who I knew had knee replacements all tell me that this was to be expected. I know from my own research that not everyone has this kind of pain and I knew my pain was abnormal and this caused me great concern. My surgeon tells me the x-rays show the replacement was successful. I would not agree with this assessment. After physical therapy, my pain is worse. I thought of canceling the physical therapy because I believed it was making my situation worse. 

I had the surgery because I was told my knee was bone on bone, there was no more cartilage. Years ago I had a torn meniscus and successful arthroscopic procedure.

I have throbbing in my knee replacement and down my leg and into the arch and heel of my foot. Some in my toes as well. These concerns all occurred after my successful knee replacement.

Complex regional pain syndrome generally appears following a physical injury, this would include knee surgery.

In 2010 I wrote in the Journal of Prolotherapy: (1)  “Complex regional pain syndrome (CRPS) is chronic pain and potentially disabling syndrome which typically affects the extremities. (Or in the case of this article, the knee). It is characterized by a variety of autonomic and vasomotor disturbances (these problems of blood flow and symptoms that this may bring). . . diffuse pain, spreading edema, temperature disturbances, and functional impairment are most prominent.

Complex regional pain syndrome generally appears following a physical injury, (this would include multiple knee surgeries) and is disproportionate to the precipitating event or level of tissue damage, (you have more knee pain than you should) and progresses inconsistently over time. It is a disease with an unpredictable and uncontrollable nature, and is a syndrome covered in controversy and confusion.” Please see our article My doctor says my knee should not hurt me as much as it does, for more information on problems that may cause excessive knee pain that cannot be documented by traditional imaging studies.

Complex regional pain syndrome is an uncommon cause of residual pain after total knee arthroplasty

In independent research, a November 2020 review paper in the journal Orthopedics (5) wrote: “Complex regional pain syndrome (CRPS) is an uncommon cause of residual pain after total knee arthroplasty (total knee replacement). The presentation (of Complex regional pain syndrome) is variable, and there is no gold standard diagnostic test. Diagnosis is more difficult after a total knee replacement because some classic signs of CRPS may be unreliable and imaging may be difficult to interpret. Early intervention is the most important factor in predicting improvement, necessitating high suspicion in patients with exaggerated pain and stiffness after excluding more common causes.”

This is the story of a patient who had significant knee pain following knee replacement

Above we heard a story of a person who had significant knee pain following knee replacement. So how do we go about helping someone like this? Here is a story of an actual patient we treated.

Our patient suffered from a long history of knee trouble. It started with two basketball-related injuries. At the tender age of nine, this young fellow tore some cartilage in his right knee and had it surgically repaired. Then at age 12, he tore his right ACL and also had it surgically repaired. For 20 years he had on and off knee pain, and at the age of 32, he sought care because he wanted to be active with his growing family and be able to maintain his job as a pharmacist. He was told he had a meniscal tear, and he was advised to have it surgically repaired. During surgery, evidence was found that the ACL was torn again, so his surgeon tried to repair it with a graft. However, his pain continued, and later that year it was determined that the new graft had torn again, and he went in for yet another ACL reconstruction surgery.

• After the last surgery, the patient’s pain level dramatically increased, and he was diagnosed with reflex sympathetic dystrophy (RSD).
  • Reflex sympathetic dystrophy (RSD) is now referred to as Complex regional pain syndrome type I (CRPS I). The diagnostic name implies exactly what it is: “Complex,” “Regional,” “Pain.” and “Syndrome.” Localized, complex pain is a “Syndrome.” A term describing that this is a difficult problem, multifactoral in symptoms with controversial suggested treatments.

Add nerve damage to the problem

• Later, as symptoms worsened the patient was then diagnosed with complex regional pain syndrome. (Complex regional pain syndrome type II (CRPS II) formerly diagnosed as causalgia, is the same as for Complex regional pain syndrome type I with the exception that nerve damage has been confirmed in the patient.)

The patient’s knee pain became so severe that an external spinal cord stimulator seemed to help, but it was never implanted. He was referred for “pain management” which consisted of taking 8 Norco^® pills (acetaminophen and hydrocodone) per day. Of course, this puts the patient at risk for side effects, and, a high risk for addiction and dependence. Two problems the patient suffered from were a 60-pound weight gain and he was tired all the time.

In this bone scan, the problems of ischemia and vasomotor disturbances (the problems of blood flow and symptoms that this may bring) are seen in a patient diagnosed with Complex Regional Pain Syndrome.

Pain and numbness in the knee

The patient’s symptoms included:

• constant numbness in the lateral knee,
• excruciating pain in the medial knee to lightest touch,
• and a general constant ache in his whole knee.

His right knee and right leg were colder to touch than the left. He also experienced numbness in both legs from thighs to feet, with numbness in the right 4th and 5th toes, cramping in the right great toe, and coldness in all right toes.

Initial consultation

The patient came to Caring Medical, and we concurred with the history of Complex regional pain syndrome type I  and type 2 diagnosis and told the patient that Caring Medical could most likely help him, but it would take a lot of work.

• The plan was to optimize his healing ability by weaning off narcotics, raising hormone levels, and improving his diet. These are ways to get the body into an anabolic (rebuilding) state from a catabolic (degenerative) state. This would ensure that the patient was in a position to get the maximum benefit from our treatments.

Bad lab results and hormonal and nutritional recommendations

As expected, his labs showed low levels of testosterone, cortisol, and DHEA, and therefore, natural hormone replacement therapy was recommended. For more information on this aspect of hormonal problems related to joint pain please see our articles: Opioids and painkillers cause low testosterone syndrome, Hormone replacement therapy, and degenerative joint disease.

Nutritional counseling and diet recommendations were also suggested. For general recommendations please see our article: What is the best diet for my knee pain?

A low-impact exercise program was also recommended. The patient was a man of faith and understood the mind, body, spirit connection as it related to his health and he worked on his faith as well as his body. As is common in chronic pain, the patient also had problems sleeping which were addressed with a prescription medication that allowed him to have restful sleep.

Does inflammation cause CRPS?

An April 2022 study in The journal of pain (7) evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee replacement.

The study participants were

• 110 osteoarthritis patients (64.5% female) undergoing unilateral total knee replacement with no prior CRPS history.
• What the researchers also observed and measured for were the following patient characteristics:
  • Domains of negative affect
    • depression
    • anxiety
    • catastrophizing
    • pain
    • sleep disturbance
    • and pro-inflammatory status – Tumor-Necrosis factor (TNF‑α)
• At 6 months, 12.7% of participants met CRPS criteria, exhibiting a “warm CRPS” (warm, burning, hot skin and joint group).
• At six weeks CRPS Severity Score (a survey evaluation of symptoms) were predicted by greater preoperative depression, anxiety, catastrophizing, temporal summation of pain (a perceived increase in intensity of pain), pain intensity, sleep disturbance, and greater pro-inflammatory status.
• Risk for CRPS following total knee replacement appears to involve preoperative central sensitization and inflammatory mechanisms. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Tumor-Necrosis factor (TNF‑α) is cell signaling protein (cytokine), which communicates the commands to create inflammation in throughout the body. It is a major player in the creation of joint swelling. The medical thinking is if you can block TNF and other inflammatory factor production or at least inhibit it, joint swelling will be reduced and hopefully the amount of articular cartilage breakdown resulting from a toxic, over inflamed joint environment will be slowed. This thinking also implicates Tumor-Necrosis factor (TNF‑α) as a factor in continued pain after surgery.

Do Spinal cord simulators help with knee pain?

Spinal cord simulators can help with lower limb pain but results are varied.

An August 2020 study in the Journal of Clinical Medicine (2) offered this simple overview of Spinal cord simulators: “The pain-relieving effects of Spinal Cord Stimulation reached significance and were comparable across all modes of stimulation including sham. Spinal Cord Stimulation was characterized by a high degree of a placebo effect. No evidence of carryover effect was observed between subsequent treatments.”

Spinal cord simulators tested better than a fake or “sham” treatment. But there was a high degree of a placebo effect. The end result is if it helps it helps and that is a good thing. But a more permanent repair treatment should also be explored.

CRPS in a woman following knee replacement

In July 2019, doctors presented a case history in the journal Case Reports in Women’s Health. (3) It describes the development of CRPS in a 69-year-old woman. Many times a patient will say to us things like: “how come you are the only ones talking about Complex Regional Pain Syndrome? We present these case histories from the medical literature to show that we are not the only people talking about this.

Here are the highlights and learning points of this research:

“While highly successful, total knee replacement has associated risks and complications. Complex regional pain syndrome is one uncommon but debilitating complication that can negatively impact patient satisfaction and quality of life. We (the authors of this study) present a case of complex regional pain syndrome in the operated leg that resulted in significant functional deficits. Key findings of this case include significant and disproportionate pain in the joint, altered cutaneous (skin temperature, touch) sensation around the joint, and decreased range of motion in flexion in the absence of any mechanical issues with the total knee replacement. Because of the debilitating nature of this condition, patients must be fully informed of and realize the risks associated with undergoing a widely appreciated procedure such as total knee replacement.”

Here is the story of the patient:

• A 69-year-old woman saw her general practitioner with pre-existing pain in her right knee that worsened following a twisting injury. No ligamentous injury was detected. Painkillers and physiotherapy were ineffective, and she was referred to (orthopedic evaluation). End-stage knee osteoarthritis was diagnosed.

The knee replacement

• The patient underwent right total knee replacement one month after diagnosis, experienced no perioperative or immediate postoperative complications, and was discharged after four days. She was prescribed discharge medications including regular paracetamol and dihydrocodeine as required for management. At a one-month telephone follow-up, there had been no postoperative complications. The patient continued exercises as directed for rehabilitation but still experienced residual swelling.

Two months later

• Two months postoperatively, the patient had pain and discomfort in the operated knee, and this was associated with altered sensations in the leg along with hypersensitivity to touch (hyperalgesia).
• The patient also mentioned that she could not tolerate even slight touch or a bedsheet over that knee (allodynia).
• Blood tests, as well as repeat imaging, produced no evidence of infection or component loosening.

Increasing doses of gabapentin

• 300 mg once per day: As she had features typical of CRPS, she was prescribed gabapentin 300 mg once per day.
• 300 mg three times per day: As the patient did not respond to the initial dose, gabapentin was increased to 300 mg three times per day, which did somewhat reduce the pain. Nonetheless, the patient continued to note a throbbing, burning sensation in the posterior aspect (back) of her knee and hyperalgesia and paresthesia on light touch over the lateral aspect.

Five months later Loss of range of motion in the knee replacement – continued pain – delayed diagnosis

• The patient in this case report appears to have experienced characteristic symptoms over this time range but did not receive a diagnosis of CRPS until over 3 months after her total knee replacement.
• The patient was referred to physiotherapy to help restore knee movement, analgesia was continued, and a pain consultant was contacted to address her CRPS. The patient continued to struggle with CRPS, despite slight improvements in pain and in range of motion five months postoperatively.

The patient wished she never had the knee replacement

• Unfortunately, the patient, in this case, found gabapentin to be of limited effectiveness. Lumbar sympathetic nerve blocks and sympathectomies are available as additional treatment options, though their long-term effectiveness is inconclusive and complications are common.
• The patient in this case emphasized her regret of undergoing total knee replacement as she noted that her quality of life was better before the procedure. This case highlights the importance of informing patients that, while total knee replacement is generally a very successful intervention for osteoarthritis, there is a risk of no improvement or worsening of pain and overall functional deficits after the procedure. Providing further clarity to the patient regarding possible outcomes of total knee replacement such as CRPS may help to ameliorate misalignments between patient expectations and the end result of surgical interventions.

Stages of CRPS

CRPS is a deteriorating disease and progresses in three stages.

• Stage I is the acute phase. In the acute phase, pain is described as burning or aching and is often aggravated by touch, emotional upset, or active/passive movement. The pain of simple injuries is much worse and lasts far longer than it should. For example, if CRPS occurs in the foot, a stubbed toe can lead to excruciating pain for up to two months. The involved limb fills with fluid and may be either hot or cold. A bone scan may show an increase of radioactive phosphate in the affected area, which indicates an increased uptake of red blood cells.
• Stage II is the dystrophic phase. In the dystrophic phase, pain is constant. The pain is exacerbated by simple movement or sensation, such as touching, vibrating, or even blowing on the limb. The affected limb becomes even more edematous (fluid-filled) as well as cool and hyperhidrosis (sweaty). There is a decreased uptake of red blood cells and bone scans reveal the initial stages of osteoporosis.
• Stage III is the atrophic stage. In the atrophic stage, irreversible damage to the extremity has occurred. The limb contracts because of limited movement. Skin becomes cool, thin, and shiny. Scar tissue has formed and because of this, it is difficult to move the joint at all. Osteoporosis and arthritis run rampant throughout the joint. This leads to a permanently frozen limb. The burning pain subsides, however at this stage, the limb is essentially useless. This process occurs over and over again in the body’s extremities.

Many doctors believe that Complex regional pain syndrome is a lack of or confused communication between the immune system, the inflammatory response, and the nervous system.  These include the sympathetic nervous system (responsible for getting the muscles ready for intense physical activity), the somatomotor system (coordination and balance), the neuroendocrine systems (metabolism, energy, heart rate), the nociceptive system (our body’s response mechanism to threat or harmful stimulus), as well as an inflammatory response.

Is it CRPS or is it NOT CRPS? Is it nerve damage caused by the knee replacement surgery?

In September 2018, doctors writing in The Journal of Knee Surgery (4) questioned the accuracy of diagnosis of CRPS in knee replacement. Instead, they speculated that the excessive challenges of a patient’s pain after knee replacement may be the result of surgical nerve damage or neuropathic pain.

They wrote:

“Previous studies suggest that complex regional pain syndrome (CRPS) occurs in up to 21% of patients following total knee replacement. However, this diagnosis has a substantial impact on the patient’s management if it is incorrect.”

The goal of this study, according to the researchers was to investigate potential causes of misdiagnosis. To do this they randomly selected a consecutive group of 100 primary knee replacement patients.

• Each patient was assessed 6-week post-knee replacement.
• Pain levels were recorded with the presence of symptoms and signs of CRPS  assessed in those with excessive pain.
• An alternative diagnosis was sought, in these patients, including the presence of neuropathic pain. (possible nerve damage from the surgery).

In the 100 patients, they observed they found no cases of CRPS. Seventeen patients (17% of the 100 consecutive patients) had excessive pain levels (nine had an alternative diagnosis explaining this).

The researchers then noted about the 8 people who did not have a diagnosis: “Using a previous definition (Orlando Criteria), eight patients may have been diagnosed with CRPS. Over half of the patients with unexplained excessive pain had evidence of neuropathic pain. CRPS is a rare diagnosis following total knee replacement using modern criteria. Isolated signs and symptoms may lead to the over-diagnosis of CRPS in the presence of unexplained pain following total knee replacement. . .  Delays in managing more common causes (such as neuropathic pain) may negatively affect the patient’s outcome.”

To date, questions about CRPS continue to be subjects of research and debate.

Treating Complex Regional Pain Syndrome in patients post knee surgery

CRPS is one of the reasons I  became so fascinated with treating chronic pain patients during medical school. Early in my career, I set out to find treatments that could actually heal the problem, not just cover it up with stronger and stronger pain medications.

CRPS treatment is based on the various mechanisms thought to cause CRPS, however since the cause is controversial, the outcomes of traditional treatment are less than optimal. Due to the disagreement overdiagnosis, there are no established treatment guidelines.

• The goal of treatment should be to first correctly diagnose the patient with CRPS.

Options available for CRPS include interventional, pharmacologic, physical/occupational therapy, and psychological techniques.

Are nerve blocks options?

• Interventional means such treatments as sympathetic or somatic nerve blocks.
  • The sympathetic ganglion blocks cause an increase in temperature to the limb due to the increased blood flow. Although the patient will experience immediate pain relief, its effect is only temporary.
  • The problem with this approach is that it does not repair damaged tissue that may be the lead contributing cause of the patient’s problems.
  • CRPS patients may even receive multiple sympathetic blocks to the point of having anesthetic pumps placed in their backs (the spinal cord stimulators mentioned above), or their sympathetic nerves may be severed in an attempt to relieve the pain.
• Pharmacologic includes narcotic pain medications, but these medications do little to restore health and limb function and frequently result in dependence on the medication.
• Physical/occupational therapy are other therapies offered.
• Antidepressants and anticonvulsants are also commonly prescribed.

Assessing the role of ligament damage and weakness in Complex Regional Pain Syndrome following multiple knee surgeries

Let’s return to the patient’s story WE STARTED ABOVE. A detailed description of the treatments will be discussed below.

Over the course of 18 months, the patient we started this article with, received 13 Prolotherapy treatments including bone marrow aspirate injections and Neurofascial Prolotherapy. These treatments comprehensively treated the ligament weakness and damage inside and around the joint capsule, as well as the small sensory nerves that had been on high alert from all the injuries and surgeries.

It took several treatments for the patient to feel incremental improvement in his knee, but he reported feeling much better on lower doses of pain meds, having higher levels of hormones, and seeing the weight steadily fall off as the treatments began and progressed.

Toward the end of his course of treatment, he was able to walk for hours with his family at the zoo and even go sledding, something he could not have imagined before starting Prolotherapy. The patient had more than the average number of necessary treatments, but he had an extraordinarily tough case of chronic pain. In addition, he had some setbacks over the course of treatment, including when a screw from one of his many procedures started to pop through his skin and exacerbated his symptoms.

Still, in cases of chronic pain after numerous surgeries and rounds of narcotic pain medications, Prolotherapy and accompanying treatments can allow a person to heal beyond what they thought possible in the “pain management” system.

Hyperbaric oxygen treatment

We are going to look at a March 2021 study in the journal Diving and hyperbaric medicine (6). This case study featured a patient who had a significant ankle injury and then a year and a half later, a significant wrist injury. I am going to present this case here in our knee discussion to introduce the treatment concept of hyperbaric oxygen treatment (HBOT) and just as important feature the doctors observation of the development of developing secondary CRPS. Here is what the doctors wrote: “A broad spectrum of conditions including neuropathic pain, complex regional pain syndrome (CRPS) and fibromyalgia, have been implicated as causes of chronic pain. There is a need for new and effective treatments that patients can tolerate without significant adverse effects. One potential intervention is hyperbaric oxygen treatment (HBOT).

In this case report, a patient received repeated hyperbaric oxygen treatment (HBOT) after developing recurrent post-traumatic CRPS of the lower as well as the upper limbs. In the first event, two months after distortion (severe twisting) and abruption (dislocation, fracture) of the external right ankle, the patient suffered leg pain, edema formation, mild (loss of blood circulation), limited mobility of the ankle and CRPS Type 1. In the second event, the same patient suffered fracture-dislocation of the distal radius (forearm bone) 1.5 years after the first injury. After the plaster cast was removed the patient developed pain, warmth, color changes, swelling and limited wrist mobility with CRPS Type 1. Pharmacological treatment as well as hyperbaric oxygen treatment (HBOT) were used with significant improvement of functional outcome in both cases. Some studies suggest that patients with a history of CRPS are more likely to develop secondary CRPS compared to the rates reported in the literature among the general population. Patients with a history of CRPS should be counselled that they may be at risk for developing secondary CRPS if they undergo surgery or sustain trauma to another extremity.”

Prolotherapy treatments for Complex Regional Pain Syndrome following multiple knee surgeries

Prolotherapy is a simple, non-surgical, in-office, injection treatment that stimulates the body’s immune system to repair painful joints. A demonstration of the treatment is displayed in the video below.

Prolotherapy is considered an alternative treatment for:

• commonly prescribed anti-inflammatory medications
• pain medications
• cortisone or steroid injection
• surgery and joint replacement

The basic concept of Prolotherapy is simple. A proliferant (something that awakens and ignites the immune system’s healing process) is injected into damaged joints and spinal ligaments or tendons, which leads to local inflammation. Prolotherapy will be used to heal soft tissue damage such as ligament injury. Prolotherapy involves injections at the site of the damaged ligament. This will initiate a local inflammatory response which will encourage blood to flow to the injured site.

Would you like to ask a question about your knee pain? Ask our Caring Medical staff

1 Ross Hauser, MD, Brinker D. The theoretical basis for and treatment of complex regional pain syndrome with prolotherapy. Journal of Prolotherapy. 2010;2(2):356-370. [Google Scholar]
2 Sokal P, Malukiewicz A, Kierońska S, et al. Sub-Perception and Supra-Perception Spinal Cord Stimulation in Chronic Pain Syndrome: A Randomized, Semi-Double-Blind, Crossover, Placebo-Controlled Trial. J Clin Med. 2020;9(9):E2810. Published 2020 Aug 31. doi:10.3390/jcm9092810 [Google Scholar]
3 Royeca JM, Cunningham CM, Pandit H, King SW. Complex regional pain syndrome as a result of total knee arthroplasty: A case report and review of literature. Case reports in women’s health. 2019 Jul 1;23:e00136. [Google Scholar]
4 Kosy JD, Middleton SW, Bradley BM, Stroud RM, Phillips JR, Toms AD. Complex regional pain syndrome after total knee arthroplasty is rare and misdiagnosis potentially hazardous—prospective study of the new diagnostic criteria in 100 patients with no cases identified. The journal of knee surgery. 2018 Sep;31(08):797-803. [Google Scholar]
5 Duenes M, Schoof L, Schwarzkopf R, Meftah M. Complex regional pain syndrome following total knee arthroplasty. Orthopedics. 2020 Nov 1;43(6):e486-91. [Google Scholar]
6 Hájek M, Chmelar D, Tlapák J, Novomeský F, Rybárová V, Klugar M. Hyperbaric oxygen treatment in recurrent development of complex regional pain syndrome: A case report. Diving and hyperbaric medicine. 2021 Mar 31;51(1):107-10. [Google Scholar]
7  Bruehl S, Billings IV FT, Anderson S, Polkowski G, Shinar A, Schildcrout J, Shi Y, Milne G, Dematteo A, Mishra P, Harden RN. Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty. The Journal of Pain. 2022 Apr 22. [Google Scholar]

This article was updated October 5, 2022

4279

• Surgery
• NSAIDs
• Cortisone Shots
• R.I.C.E.