Overview and Symptoms
- What are the causes of NCCP?
The sources of NCPP can be grouped into esophageal and non-esophageal. Several studies have shown that approximately 60% or more of patients with NCCP suffer from acid reflux (mostly due to what is commonly referred to as Gastroesophageal Reflux Disease). Therefore, patients having chest pain who have had a negative cardiac evaluation are frequently referred to gastroenterologists (digestive disease specialists) to evaluate the esophagus as source of their chest pain.
- Esophageal Sources of NCCP:
- Gastroesophageal Reflux Disease (GERD) or acid reflux
By far the most common cause of esophageal NCCP is gastroesophageal reflux disease also known as GERD or acid reflux. Studies estimate that between 22-66% of patients have GERD as a source of NCCP. In addition to chest pain, patients may complain of heartburn and or regurgitation or chest pain alone may be due GERD.
- Esophageal contraction disorders as cause of NCCP:
Other esophageal causes of chest pain include disorders of esophagus muscle (esophageal motility disorders) such as uncoordinated muscle contractions (esophageal spasm), contractions of extremely high pressure (nutcracker esophagus), and occasionally a disorder characterized by absence of esophageal muscle contraction due to loss of nerve cells of the esophagus (achalasia). It is important to recognize particularly achalasia since is a treatable disorder.
- Visceral (esophageal) Hypersensitivity:
Patients with NCCP may also have “visceral hypersensitivity” that is an esophagus where the smallest change in pressure or exposure to acid may result in tremendous pain. This is best explained by describing an experiment: when a small balloon is placed inside the (esophagus) and distended, patients with NCCP perceive the distension of the balloon at very low volumes. This is unlike healthy control subjects who do not experience this pain at all or may only have pain when the balloon distension reaches very large volumes. This phenomenon has been termed “Esophageal or visceral hypersensitivity” (enhanced esophageal perception or sensitivity to balloon distension). Although the cause of this increased sensitivity to balloon distension is unknown, there are treatment modalities that can be used to improve this exaggerated pain perception.
- Non-esophageal Causes of NCCP
NCCP is a common disorder with esophageal causes (described above) and nonesophageal related causes.
Non-esophageal sources that can cause NCCP include: Musculo-skeletal conditions of the chest wall or spine, pulmonary (lung) disorders, pleural illness (the layers of tissue that cover the lungs), pericardial conditions (the layer of tissue that protects the heart) and even digestive disorders such as ulcers, gallbladder, pancreatic diseases and rarely tumors (particularly in patients past age 50).
The Role of Stress:
Some of patients with NCCP have also been found to suffer from stress that leads to disturbances such as depression, anxiety or panic disorder. It is unclear whether the stress disorder came first or the chest pain led to the appearance of an emotional disorder. Treatment of these conditions is an important component of treating chest pain.
NCCP can occur in children as well as older patients, it also affects men and women and some studies have suggested a higher proportion of patients are female. The reasons some studies have found women may have a higher frequency of NCCP than men is not well understood.
NCCP is a very common problem of international proportions. Population studies have shown that in the United States as many as 70 million patients (23% of the population) suffer from NCCP. Similar figures have been described in Australia (33%), Spain (8-28%), Argentina (24%), and South China (21%). No other specific risk factors have been identified.
- What do I do if I’ve been treated for chest pain, but told I didn’t have a heart attack?
Patients suffering from chest pain must have thorough cardiac evaluations to ensure they do not have heart disease prior to being labeled as having NCCP. In addition, a variety of other disorders described above, both esophageal and non-esophageal must also be considered since specific treatment for these disorders are available.
Once cardiac tests have concluded that patients do not have heart disease, patients are commonly offered a treatment trial of acid suppressive inhibition medications (called a PPI - proton pump inhibitor - trial) for about 2 weeks. This is frequently referred as “a PPI trial” and can be both diagnostic and therapeutic since if it relieves the chest pain it suggests that acid-reflux is likely the cause. Thus, if pain is improved the treatment may be extended for a longer period of time such as 2 months. If the patient does not improve after “a PPI trial”, further testing may be done. Those studies may include a pH study of the esophagus (a test to actually measure the amount and determine if there is acid reflux) an upper endoscopy (a scope with a light that is introduced in the esophagus and stomach to check for other conditions that may cause chest pain), an esophageal motility test (a test to study the esophagus muscle contractions) and perhaps an ultrasound of the abdomen to examine the gallbladder for possible stones.
- Patients may be treated as if the NCCP was a result of having GERD:
Once cardiac and other life-threatening conditions have been excluded and, based on the notion that the most common cause of NCCP is GERD, a treatment trial is frequently considered.
Patients are often prescribed a proton pump inhibitor (PPI) also called a PPI trial. They must be taken at least 30-60 minutes before breakfast. It has been shown that this approach produces an approximately 80% response rate for patients with GERD-related NCCP.
If the patient responds, the treatment can be continued for at least 8 weeks at a reduced dose such as Omeprazole (or equivalent PPI medication ) 20 mg twice daily about 40 min prior to meals. Other equivalent PPI’s can also be employed and include: Esomeprazole, Lansoprazole, Rabeprazole, and Pantoprazole.
- For patients not responding to a PPI, GERD is the unlikely source of pain:
For these patients, other medications are available. These medications are felt to produce their favorable effect by reducing pain transmission from the esophagus to the brain. The medications often used are low doses and are from the class of drugs known as tricyclic antidepressants (TCAs), and not used at the high doses employed for the treatment of depression.
Commonly used agents are amitriptyline, nortriptyline, desipramine, imipramine and trazodone. The two most commonly used agents are imipramine and trazodone. While for the most part they are safe, side effects may include sleepiness, dry mouth, blurred vision and urinary retention. Trazodone can also cause a sustained erection (called priapism), which is considered a medical emergency.
Other categories of antidepressants – such as “selective serotonin reuptake inhibitors” or SSRI” – can be tried if TCA are not tolerated because of side effects. Two recent reports suggest that the SSRI Sertraline may also have a beneficial effect in the treatment of NCCP. This medicine was found to be more effective than placebo (a sugar pill or an inert substance) in the treatment of NCCP. New studies are also being done to explore other SSRI’s like paroxetin, fluoxetin and citalopram. Also recent studies have found potential benefit with the Serotonin and Noradrenalin Reuptake Inhibitor (SNRI) called Venlafaxine. For patients not responding to either acid inhibition trial or TCA or other antidepressants, esophageal motility testing (a study done to evaluate the muscle contractions of the swallowing pipe) may be done to look for other uncommon causes of chest pain such as achalasia. This is particularly important since achalasia is a treatable disorder.
A number of studies continue to be done to better understand the mechanism(s) of pain in NCCP. Furthermore, new treatment agents are being investigated. A recent study suggested that receptors in the esophagus, such as the so called adenosine receptors, may account for visceral pain in NCCP. Using a medication that acts on these receptors (Theophilline) a group of investigators showed it may be effective for the treatment of NCCP. However, side effects of this particular agent may limit its use. Thus, in the future newer medications that act on these adenosine receptors but that have a better margin of safety may provide new opportunities for the treatment of this challenging condition.
- Management of stress:
If patients do not respond to the above approach or they suffer from depression, anxiety, and/or panic disorder, they should be referred for appropriate psychiatric consultation and treatment. Several recent studies have also found that Cognitive Behavioral Therapy (CBT) or “talk therapy” and relaxation training techniques is effective in improving NCCP when compared to patients on a waiting list. Other brief preliminary reports have also found that hypnosis may also help selected patients with NCCP.
Author(s) and Publication Date(s)
Sami R. Achem, MD, FACG, Mayo College of Medicine, Mayo Clinic, Jacksonville, FL – Published February 2009. Updated July 2013.
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