Persistent Pediatric Pain: New Paradigms, Improved Prognoses

FEBRUARY 20, 2012
SJ Kizilbash, TE Harrison, RT Wilder, SW Driscoll, BK Bruce, PR Fischer
In recent years, physicians’ thinking has changed when it comes to evaluating pain in patients. Now, rather than looking at pain as being merely a symptom of an underlying disorder, many clinicians are now focusing on the pain itself, and changing their approach to how they treat it.

Pain happens. And that’s not necessarily a bad thing. Short-term acute pain can be helpful. Like a “stop ahead” sign, it warns of upcoming danger so we can take action to prevent worse problems. For example, severe right lower-quadrant abdominal pain prompts a visit to an emergency department so corrective appendectomy can prevent severe complications of a ruptured appendix. Severe leg pain after a fall stimulates a visit to a health care provider so a fracture can be splinted and crippling deformity avoided. Acute pain is helpful when it leads to protective action.

Perspectives on chronic pain
Sometimes, however, pain persists. Sometimes it recurs. Sometimes it never seems to go away. Pain hinders routine activity for about one-third of American adolescents1 and some are disabled by pain. Whether the inciting trigger for the pain remains or not, the pain can persist. Sometimes extensive medical evaluations reveal no ongoing “cause” of the pain. Operations and evaluations don’t help. In these cases, the pain has become the problem rather than serving as a warning of other potential problems.

Professionals once operated under the notion that chronic pain, like acute pain, was a warning sign of an underlying problem that required a diagnosis so as to determine curative therapy for the underlying etiology. The doctor’s role was to discover a diagnosis. In the event he or she was unable to do so, he or she then was left to prescribe drugs for the pain while the patient was left discouraged, dysfunctional, and disabled.

Now, there is an increasing realization that chronic pain often is the problem. Rather than being the sign marking the presence of underlying pathology, chronic pain is often the diagnosis itself; there is often no hidden disease. Under this new paradigm, the physician provides the patient with a new perspective. The patient then participates in a multi-faceted pain management program so as to make progress in achieving the promise of renewed productivity.

Philip Fischer, MD

Philip Fischer, MD


"There is an increasing realization that chronic pain often is the problem. Rather than being the sign marking the presence of underlying pathology, chronic pain is often the diagnosis itself."

As paradigms shift, we think that doctors need to learn to avoid medications that merely numb the pain and cause side effects. Patients need to see pain as the key problem, rather than pursue a frustrating search for better doctors and rare diagnoses. Working together, the physician can help the patient overcome the pain, regain full function, and find more complete physical, mental, and emotional health.

Physicians, therefore, must be able to determine whether the adolescent presenting with pain has a dangerous condition or whether the pain has outlived the trigger and become the problem in and of itself. If the pain has become the problem, then the pain must be managed effectively, instead of pursuing unhelpful secondary and tertiary evaluations and tests.

In fact, chronic pain with no identifiable underlying cause calls for a change in paradigm. We must shift from a painprovoked pursuit of a problem toward a rehabilitative recipe for recovery. Acute pain usually results from a stimulus at the site of nerve endings. Chronic pain, however, comes from dysfunction elsewhere along the pathway from the nerve through the subconscious mind to the brain. Thus, chronic pain management requires multifaceted interventions at multiple areas along the dysfunctional sensory nervous system.

Case example: A 15-year-old with abdominal pain
Consider, for example, the case of a 15-year old boy with eight months of abdominal discomfort that started after a spring break trip to Central America. His pain has lasted for many months without weight loss or other signs of serious systemic disease. The history can give clues about the pain source within the sensory nervous system. If, for instance, the pain started after some sexual indiscretions and the patient reports being afraid that his father will find out, we might suspect that the pain is originating above the neck. If, however, the pain is associated with bloody diarrhea and iron deficiency anemia, we might suspect there is inflammatory bowel disease. Intermittently loose stools with abnormally high levels of tissue transglutamase (TTG) would prompt consideration of celiac disease, endoscopy, and possible institution of a glutenfree diet. In this case, however, the patient had what seemed like traveler’s diarrhea at the end of his Central American trip, seemed to get better but then continued to have some irregular stooling with chronically recurring abdominal pain. Stool evaluations for parasites and bacterial pathogens were negative. Upper and lower endoscopy yielded normal findings. There was no evidence of intolerance to any dietary sugar. The patient was thought to have post-infectious irritable bowel syndrome.

Barbara Bruce

Barbara Bruce, Ph.D., L.P.

So, what was this patient’s problem? Approximately 10% of individuals who get traveler’s diarrhea or other forms of infectious colitis go on to develop irritable bowel syndrome. The problem seems to originate in the gastrointestinal tract with post-infectious post-inflammatory alterations in motility. Or, does it? Is the problem in the GI tract or in the nerves near the GI tract or in the brain?

The etiology of irritable bowel syndrome (IBS) is not clearly understood. However, there is a general consensus that the clinical manifestations represent a dysregulation in the interplay of events between the gut and the nervous system, leading to changes in sensation (hyperalgesia) and motility. Mucosal biopsies from patients with IBS have shown neuroplastic changes in the gut epithelium. It is thought that these changes lead to peripheral sensitization of the nerve endings, resulting in enhanced sensitivity to stimuli (visceral hyperalgesia). Prior gastroenteritis, genetics, luminal irritants, changes in the microbial flora, mucosal inflammation or immune activation have been implicated in these changes. Epidemiological evidence links exacerbation of symptoms of IBS with psychosocial stressors. It is therefore likely that psychosocial stressors somehow impact the dysregulation between the gut and the brain.

There is substantial evidence suggesting central pain amplification in the pathogenesis of IBS. One of the mechanisms proposed is activation of spinal glia in response to psychological stress or visceral inflammation, which leads to upregulation of certain receptors (NMDA) and results in central sensitization. Functional MRI studies have shown a difference in brain response to balloon rectal distension between healthy controls and patients with IBS. These patients show consistent activation in the region of the brain associated with stress and arousal circuits as well as in the regions associated with pain modulation (increased engagement of pain facilitatory mechanisms and decreased activity of endogenous pain inhibitory mechanisms). Furthermore, compared to healthy controls, patients with IBS show increased gray matter density in the areas involved in stress and arousal circuits. These findings support the hypothesis that changes in central pain modulation play a role in perception of pain. Additionally, there is an association between stress circuits and sensitivity to pain.

Management of IBS requires both pharmacological and nonpharmacological components. The pharmacological therapy may be symptom-directed (such as pain control with analgesics) or may target several sites in the brain-gut axis (serotonin antagonist). Cognitive behavioral therapy and hypnosis have been shown to be effective in several clinical trials.8 It is thought that these approaches reestablish the brain pathways by enhancing the inhibitory control mechanisms and regulating the stress and arousal circuits. Hence, the approach to successful management of IBS is multifaceted.

Clearly, chronic pain should prompt us to provide “wholistic care,” treating the whole patient rather than just one organ system. Whether the pain seems to be triggered by “mental” shame and guilt feelings or whether the pain seems to come from “physical” post-infectious dysmotility, we must treat the patient’s whole nervous system and, in fact, the whole patient who has that nervous system.

Sheri Driscoll

Sheri Driscoll, MD

A 15-year-old girl with headache
Consider the case of a 15-year-old girl who was a high-achieving straight-A student, president of a school service club, and leading scorer on both the basketball and volleyball teams at her school. She developed fever and a sore throat with positive heterophile antibodies. The “mono” resolved over a month, but she remained fatigued with daily headaches and postural dizziness. Is this young woman’s problem physical? Is it emotional? Is it mental? We would answer “Yes, yes, and yes”‑‑ the whole person is suffering.

Evaluation of this adolescent included a normal head MRI, repeatedly normal blood and urine tests, and a psychologic evaluation revealing discouragement with her physical condition but no real psychopathology. Tilt table testing, however, revealed postural tachycardia of 48 beats per minute. Does she have postural orthostatic tachycardia syndrome or deconditioning, or “just” new onset post-viral chronic daily headaches?

Postural orthostatic tachycardia syndrome (POTS) is a form of autonomic dysfunction that is commonly linked to chronic fatigue and chronic pain. The typical affected adolescent was high-achieving and then was temporarily incapacitated with an illness or injury. Well after the inciting illness or injury resolved, the patient remains tired and uncomfortable, often with dizziness and nausea. Head-up tilt testing reveals postural tachycardia of greater than 40 beats per minute.

Interestingly, about two-thirds of patients with presenting symptoms like these have postural tachycardia syndrome and about two-thirds are deconditioned with lower than normal maximum oxygen uptake on exercise testing. POTS and deconditioning overlap in some but not all of these patients.12 Treatment must target improvements in autonomic function and in conditioning, as well as managing sleep deprivation and anything else adversely affecting the patient.

Can discouragement and/or depression cause chronic fatigue with chronic headaches? Certainly, they can. Effective treatment regimens will incorporate wholistic approaches for the body, mind, and emotions of the patient.

What should we do for tired, hurting teenagers? We should treat the whole person. If there is postural tachycardia, we will try to increase the circulating blood volume by encouraging increased fluid intake (enough so as to make the urine look clear like water) and increased salt intake. We would consider medications such as beta blockers and midodrine to facilitate improved blood flow.9 However, the foundation of treatment of autonomic dysfunction is exercise. The foundation of treatment of deconditioning is exercise.

Interestingly, the same neurotransmitters that relate to depression and anxiety in the brain also relate to autonomic control of blood flow. Selective serotonin reuptake inhibitors (SSRIs) are helpful for both conditions. Is the problem primarily medical or mental? Yes! Whether we are treating an adolescent with irritable bowel syndrome or autonomic dysfunction or depression or any other cause of pain, we should treat the whole patient.

Bob Wilder

Bob Wilder, MD, Ph.D.

Managing chronic pain
What do we do for an adolescent with chronic pain? Initially, we listen and we validate. There is no such thing as artificial pain. If the patient says something hurts, it hurts. Whether the current cause of pain is inflammation, injury at the nerve ending, dysfunctional nerve transmission, or altered mental interpretation of incoming sensory nerve messages, the pain is real. We can validate the patient. The pain is not just “in his or her head.”

Second, we can ensure that a reasonable search for active triggers to the pain is done. If nothing is identified, we can reassure the patient and his or her family that the pain will be treatable and that recovery is likely. However, they must also understand that it will take time, and a multi-faceted approach to resolve the pain and achieve recovery will be required.

We will explain to the patient that the problem is “confused nerve” pain rather than a dangerous pathology near the nerve endings. This means that we will use multiple concurrent approaches to help the pain.

Since some nerves are sending unhelpful messages (warning of danger to be avoided when there is none), we need to ensure that surrounding nerves are being fully used so that helpful, positive nerve messages are coming from other parts of the nervous system. Deep diaphragmatic breathing techniques are particularly helpful when the pain seems to the patient to be coming from the abdomen.

We should also look for easily treatable conditions that might be exacerbating the pain. Half of chronically tired teenagers, especially those with autonomic dysfunction, are iron deficient as noted by a ferritin level of less than 20 ng/mL. One-third or more of adolescents with chronic pain are vitamin D deficient. It is not clear how iron and vitamin D confound chronic pain and fatigue, but treatment is reasonable when deficiencies are identified.

Activity and exercise are critically important to recovery. Patients who have recovered from chronic pain and fatigue are the most vocal advocates for similarly affected adolescents to stay in school and to exercise daily. Parked cars don’t change direction no matter how much the steering wheel is turned. Similarly, inactive bodies don’t fully recover no matter how well the cells and nerves are treated. Tired, hurting teenagers must include daily aerobic exercise in their recovery plans.

Some teens may not be able to initially sustain aerobic activity such as walking for more than 5-10 minutes at a time. They should begin a daily aerobic exercise plan with the amount of time they can tolerate without exacerbation of symptoms. Gradually increasing the duration of aerobic exercise toward a goal of thirty to sixty minutes is recommended. Stretching and strengthening exercises can also be of benefit for many adolescents. A personalized exercise plan can be developed to target specific problem areas.

Tracy Harrison

Tracy Harrison, MD

For localized pain, trancutaneous electrical nerve stimulation (TENS) devices may be effective. TENS is a non-invasive, low risk, electrotherapeutic modality which is widely available. An adolescent can learn to use the modality independently as needed for pain control. Other simple modalities such as heat and ice may also be temporarily helpful. More sophisticated pain relieving modalities can be provided by a physical therapist.

Medications can help, too. But, narcotics dull the sensory nervous system, risk adverse gastrointestinal effects, and end up delaying recovery. There is not a valuable role for narcotics for treating chronic pain in adolescents without an underlying active pathology such as recurring fractures with osteogenesis imperfecta. Even then, different medications designed for chronic nerve pain are often more effective. Topical amitriptyline and lidocaine are sometimes effective at the site of the pain. Stabilizers of nerve transmission like amitriptyline, nortriptyline, and gabapentin can be very effective. The Table notes doses and details of administration. SSRIs and selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) can sometimes help stabilize both brain and nerve aspects of neuropathic pain. Medications, however, should not be expected to eliminate pain. Rather, they should be viewed as one important component of a multifaceted pain management strategy. Recovery from chronic pain is possible, but it takes time.

Related >>> View a Pain Medications chart related to this article

Any patient with a chronic health condition, but especially those with pain, can benefit from “mind over body” biobehavioral interventions. From deep diaphragmatic breathing to relaxation strategies to biofeedback to cognitive behavioral therapy, a wealth of techniques are available to help patients regain control over their dysfunctional nervous systems. Innovative programs are being developed to assist the adolescents with chronic pain who are at most risk of forfeiting their education because of incapacitating symptoms and are showing success at returning these teens back to school. The most debilitated teens may benefit from a multidisciplinary pain rehabilitation approach which uses pain management strategies together with physical therapy, endurance training, occupational therapy, and skills for managing the comorbid struggles these teens often face such as depression, school bullying, family distress and moving out of the sick role.

Sarah Kizilbash

Sarah Kizilbash, MD

Time Magazine got it right in a March 2011 cover story that suggested that “we need to do more than simply muffle the nervous system’s false alarms so the brain and body don’t hear them. Instead, we have to retrain the brain and find a way to shut that alarm down.” Indeed, pain management is entering a new day. The paradigm is shifting. Acute pain management strategies are now known to be inappropriate for chronic pain. Multifaceted treatment programs are needed to combat chronic pain. Physicians and patients need to align perspectives and plans to move patients from dysfunction and disability toward rehabilitation and recovery. For adolescents who struggle to do this with intermittent visits, intensive multi-week pain programs can be effective.

Hearing about Americans with chronic abdominal pain, an Asian neurologist commented, “I know what they need. They need to make their mind the master and their body the servant.” Indeed, in the new world of successful pain management, the patient must be empowered to use his or her good mind to help modify and reinterpret incoming nerve stimuli and to maintain good activity and exercise even when that goes against the incoming inhibitory messages from the body. The pain is not “all in their heads,” but the recovery does partly come from their mind.

Yes, pain happens. Persistent and recurrent chronic pain can be debilitating. But, restoration of health and activities is possible with careful evaluation and multidisciplinary management. Focusing on new understandings of pain, aggravating comorbid conditions can be identified while also seeing the actual pain as a key diagnosis on which to focus multiple therapeutic interventions. Over time, good recovery is usually possible.


The authors work together at the Mayo Clinic in Rochester, Minnesota, to care for adolescents with chronic pain. Sarah Kizilbash and Phil Fischer are general pediatricians. Tracy Harrison and Bob Wilder are pediatric anesthesiologists specializing in pain medicine. Sheri Driscoll is a physiatrist. Barbara Bruce is a psychologist. Each of the authors is on the faculty of the Mayo Medical School.

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