When people have a heart attack, a classic symptom is shooting pain down the left arm. That symptom, it turns out, has something in common with a far more benign kind of pain: the headache one can get from eating ice cream too fast.
Both are examples of what doctors call referred pain, or pain in an area of the body other than where it originates. Such sensory red herrings include a toothache resulting from a strained upper back, foot soreness caused by a tumor in the uterus, and hip discomfort when the problem is really arthritis in the knee.
Referred pain can make diagnoses difficult and can lead to off-target or wholly unnecessary cortisone injections, tooth extractions and operations. Now, in trying to discover the patterns and causes of the phenomenon, researchers say they are gaining a greater understanding of how the nervous system works and how its signals can go awry.
“The body can really fool you in terms of determining pathology,” said Karen J. Berkley, a professor of neuroscience at Florida State University. Her research has focused on referred pain caused by endometriosis — pain that can be felt as far away as the jaw.
One possible explanation has to do with the way the body’s nerve fibers converge on and send signals up the spinal column. Each nerve input carries an astonishing amount of information about the body.
“What we think happens is that the information sometimes loses its specificity as it makes its way up the spinal column to the brain,” Dr. Berkley said. In the constant dynamic of excitation and inhibition that occurs during the transport of innumerable nerve impulses, she went on, “we can’t always discern where a sensory message is coming from.”
Usually the mixed signals come from nerves that overlap as they enter the spinal column — from the heart and left arm, for example, or from the gallbladder and right shoulder. This so-called adjacency of neural inputs probably explains why some people report a sensation in their thighs when they need to have a bowel movement or feel a tingling in their toes during an orgasm.
Moreover, when the stimulus emanates from internal organs, the sensation is often perceived as coming from the chest, arms, legs, hands or feet. “The brain is more used to feeling something out there than in the viscera,” explained Gerald F. Gebhart, director of the Center for Pain Research at the University of Pittsburgh.
In a study published last year, researchers at Aalborg University in Denmark applied irritating substances like capsaicin (the stuff that makes chili peppers hot) to subjects’ small and large intestines. They found increased blood flow and elevated temperatures in referred-pain sites in the trunk and extremities. (The study appeared in The European Journal of Pain.)
Pain can also be referred to areas that do not have overlapping nerves. This most often occurs after an injury, according to Dr. Jon Levine, a neuroscientist at the University of California, San Francisco. This, he said, might be because of “pain memory,” which makes the brain more likely to “experience a new sensation as coming from where you were hurt before.”
Several studies using functional magnetic resonance imaging have supported this hypothesis. Areas of the brain corresponding to once injured body parts often lit up when another part was poked or prodded.
Widespread and persistent inflammation in response to a current or past injury may cause what doctors call peripheral sensitization, or excitation of nerves elsewhere in the body. These somatic nerves are on high alert and ready to fire pain signals at the least provocation. Dr. Emeran A. Mayer, a gastroenterologist at the University of California, Los Angeles, who studies referred pain from the gut, said, “The more pain a person has experienced or is experiencing, the more likely we are to see atypical sites of referral.”
Referred pain is also thought to emanate from trigger points — taut nodules that develop within muscle — which were first described in the 1960s by Dr. Janet G. Travell, who treated President John F. Kennedy ’s back pain. The matrix of trigger points and their predictable pain-referral patterns has “a remarkable correspondence with acupuncture meridians in Chinese medicine,” said Dr. Jay P. Shah, a physiatrist in the rehabilitation medicine department at the National Institutes of Health.
Patients report that their referred pain is precipitated or worsened when the corresponding trigger point is pressed, and alleviated through massage or acupuncture at the trigger point. Though some doctors are skeptical about the trigger point hypothesis, Dr. Shah published a study last year in The Archives of Physical Medicine and Rehabilitation indicating that inflammatory chemicals exist at both the trigger points and the locations of referred pain.
Researchers say the varied explanations for referred pain may not be contradictory, but rather an indication that several mechanisms are at work. Dr. Lars Arendt-Nielsen, head of research at the Center for Sensory Motor Interaction at Aalborg, said the growing body of evidence supporting each notion “has changed the way we treat pain to a multifaceted approach.”
Treatments might incorporate not just painkillers but drugs that calm the central nervous system, like anti-epileptics and serotonin reuptake inhibitors.
Acupuncture and trigger-point therapy have also gained acceptance, along with psychological approaches that encourage patients to focus on where the pain is actually coming from rather than where it hurts. Research conducted in 2003 at the University of Bath in England and published in the British journal Rheumatology revealed that patients’ referred pain diminished or disappeared if they saw where the pressure was actually being applied.
“Patients and doctors alike,” said Dr. Berkley, of Florida State, “need to remind themselves that where pain is felt may not be where the problem lies.”
September 16, 2008