Centralized pain is fast emerging as a critical factor in therapeutic, diagnostic, and medical-legal issues. Knowledge about centralized pain has rapidly spread into the public, and the supporting organizations and institutions around medical practice. It is now highly recommended that every chronic pain patient be evaluated for the presence of centralized pain. If present, a diagnosis of “centralized pain” should be given in addition to whatever primary diagnosis is given. For example, a primary diagnosis of “lumbar spine degeneration” would carry a secondary diagnosis of “centralized pain.”
How Centralized Pain Develops
If a peripheral injury doesn’t heal and completely resolve its acute pain, inflammatory mediators from the injury site and possibly electronic signals enter the spinal cord and central nervous system (CNS) (Figure 1, page 56). Microglial cells activate and produce neuroinflammation. Neuron hyperexcitability, known as “central sensitization,” occurs. Glutamate and other excitatory amino acids are released in the inflammatory process causing tissue destruction in the CNS. In this process, memory of the pain somehow becomes permanently imprinted. The inflamed, hyperexcited tissue in the CNS causes excess efferent electronic signals manifested by allodynia and hyperalgesia. Excess sympathetic discharge occurs and hypothalamic-pituitary stimulation increases adrenal hormone production. Centralized pain, with its underlying neuroinflammation and hyperexcitable manifestations, displays a characteristic clinical profile, which can be assumed and diagnosed by history and physical.
Characteristic Clinical Profile
The hallmark of centralized pain is that patients report their pain to be “constant,” which usually has been so since their injury or surgery; patients feel its presence “24/7” (Table 1). It never goes away unless the patient is asleep. Although terms such as “persistent,” “chronic,” or “intractable” may be applied to a patient for any number of medical or legal reasons, the key point is that pain is constant. If pain is intermittent or episodic it is likely peripheral in nature. Just know that the memory of pain is imprinted or imbedded in the CNS and remains ever present in centralized pain.
The inflamed, hyperexcitable CNS puts out excess electronic signals through its efferent and sympathetic systems giving rise to tachycardia, hypertension, and periodic bouts of allodynia (pain to light touch) and hyperalgesia (excess pain on pressure). Patients may complain of episodes of burning, crawling, or stabbing. Insomnia is always present and probably related to the hyperexcitable CNS. Excess sympathetic discharge is manifested by vasoconstriction (cold hands and feet), mydriasis (dilated pupil), hyperhydrosis, tachycardia, hypertension, and hyperreflexia. Patients historically report poor or zero response to peripheral pain treatments such as local anesthetics, cortisone injections, acupuncture, and electromagnetic measures.
Laboratory Testing
If the history and physical suggests the possibility of “centralized pain,” the common inflammatory markers, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) should be tested. These are non-specific markers of inflammation, including neuroinflammation. If these markers are elevated, it likely means there is CNS inflammation and ongoing tissue destruction. In addition to these two simple inflammatory markers, it is advisable to do some basic hormonal testing such as a serum cortisol and pregnenolone test. Centralized pain causes overstimulation of the hypothalamus and pituitary that initiates a hormonal cascade producing elevated serum pregnenolone and cortisol. If centralized pain goes uncontrolled for an excessive time period, adrenal hormones including cortisol and pregnenolone may be suppressed and show low serum levels. In summary, abnormal inflammatory markers and/or hormone serum levels are strong biologic evidence that centralized pain is present. More important is if you believe centralized pain is present, laboratory testing is warranted.
A Tip on Diagnosing Centralized Pain
The diagnosis of “centralized pain” is strictly a clinical diagnosis. Even though magnetic resonance imaging (MRIs) may show brain atrophy and laboratory testing may show elevated inflammatory markers or hormone abnormalities, they are only contributing components to the diagnosis.
In addition to the clinical characteristics listed in Table 1, I like to do the following as a simple test. I apply 5% lidocaine over the painful, peripheral area and apply heat, massage, infrared, or radiowave over the lidocaine for 5 minutes. If the patient gets no relief, I assume there is little or no active, inflammatory peripheral pain site, and the pain must, therefore, be central.
Listed here, not necessarily in order of importance, are benefits of clinically diagnosing centralized pain and entering it into the patient’s record (Table 2).
Opioid Treatment
Since the hallmark of centralized pain is constancy, opioids—including a high-dose opioid regimen—may be necessary to control pain. The FDA’s approved labels for long-acting opioids are only to be used “when around-the-clock dosing is indicated.” This label can be found for each agent in the Physician’s Desk Reference (PDR). Constant pain is the primary indication for “around-the-clock” dosing. High or ultra-high opioid dosages may be necessary to control centralized pain and its attendant complications including hormonal abnormalities, inflammation, insomnia, and excess sympathetic discharge (ie, tachycardia). The major point is that a diagnosis of centralized pain is now essentially a necessity to warrant long-acting opioids for around-the-clock dosing.
Recognition of Pseudoaddiction
The hyperexcitable and inflamed CNS of centralized pain may cause patients to desperately seek pharmacologic relief. Patients with centralized pain often describe an intolerable, dysphoric, suffering state that may drive them to great lengths in seeking pharmaceutical relief with an opioid, benzodiazepine, or alcohol. With our new understanding of centralized pain, every patient who appears to be drug seeking should be evaluated for centralized pain. For example, the following case report is illustrative.
Case Report
A 50-year-old woman with cervical spine degeneration had been to eight physicians and made 20 visits to an emergency room in the past year to obtain opioids. She had not found relief with epidural corticoid injections, acupuncture, topical medication, antidepressants, neuropathic drugs, and anti-inflammatory agents. She was labeled a “drug addict.” She described her pain as constant and suffered severe insomnia. Physical exam revealed cold hands and feet, dilated pupils, hyperactive reflexes, and tachycardia—heart rate of 110 beats per minute. After recognizing she had centralized pain, a blood test was taken, which showed elevated CRP and serum cortisol concentration. Her daily opioid intake was progressively raised over a 6-week period from 50 to 400 mg of morphine equivalence per day. She immediately stopped visiting emergency rooms and seeking out doctors to obtain pain relief.
Identify Depression
Depression is an integral component of centralized pain. The neuroinflammation, hormonal disturbances, and tissue destruction involved with centralized pain invariably cause depression. It is for this reason that an antidepressant, along with an anti-inflammatory agent, make a good first-line treatment approach.
Intractable Pain Laws and Guidelines
Without even knowing centralized pain exists, many states have passed intractable pain laws or developed guidelines to allow physicians to prescribe opioids. These laws were primarily passed some years ago, at which time there was no understanding about centralized pain. Most of the states have a statement in their intractable pain laws or guidelines that implies there is “no cure by any known means.” In most cases, this statement unknowingly refers to patients with centralized pain. Regardless of terminology, there is no known cure for centralized pain, and physicians must educate all parties to this fact. We can usually control and reduce the pain, but we can’t claim any cure at this time.
We physicians also need to urgently educate all concerned parties—family, third-party payors, regulators, patient advocacy groups, and media—about centralized pain. There’s no better way to educate than putting a diagnosis of centralized pain on all correspondence, bills, laboratory requests, reports, and prescriptions.
Mental Deterioration—Be Prepared
The neuroinflammatory process associated with centralized pain randomly destroys cellular tissue.¹ This mere fact helps explain why centralized pain patients will display slightly different symptoms from each other and respond to different treatments. Unfortunately, the CNS tissue destruction in centralized pain that can occur may result in loss of brain mass, mental deterioration, and even dementia. Brain studies are clear—centralized pain is associated with loss of brain tissue.¹⁻³
A New Treatment Delivery Approach Is Needed
Centralized pain patients need a unique treatment approach. Physicians everywhere are starting to set special hours, train staff, and create new clinical forms and records to treat these unfortunate individuals. Urine and blood testing for drugs of abuse and clinical compliance are now in the forefront, as they should be. Some of these patients may deteriorate mentally and need at-home nursing and social services, as they may not be able to totally care for themselves. In summary, these patients may need to be separated from general medical patients.
Disability Evaluations
The incurable status and special needs of the centralized pain patient need to be an integral part of physician reports and recommendations, which involve worker’s compensation and disability cases. If centralized pain is not clearly described, concerned parties may view the patient as having the simple requirements of a patient with a common arthritis or degenerative, peripheral pain problem. Worse, they may believe the patient to be a drug seeker. Parties who pay for the medical cure of central pain patients may feel it to be expensive. They will, however, find that a rejection of the diagnosis and failure to properly manage the case will be a more expensive waste of time, as the patient will be involuntarily subjected to a lot of expensive and useless peripheral treatments, psychiatric evaluations, and procedures.
Prevention of Centralized Pain
There is no better reason to determine whether centralized pain is present than to find out it is absent. Centralized pain is very difficult to manage, and, barring some scientific breakthrough, it is a life-long condition. Peripheral pain, on the other hand, is very controllable and treatable. Most important, peripheral pain should be vigorously treated with the knowledge that it could become centralized.⁴
Medical-Legal-Regulatory Issue
The federal government and, essentially, all states have pain treatment laws and guidelines. Physicians need to clearly identify patients who have centralized pain, peripheral pain, or both. This assessment needs to be in every medical record. Why? Centralized pain patients will be those who require aggressive treatment regimens, which may include high-dose opioids. Before a regulator decides to “count pills,” they should know whether they are reviewing a centralized pain patient.
Summary
The understanding of how a peripheral nerve injury from a surgery, accident, or disease can transform into centralized pain is a profound discovery that is fast beginning to alter medical thinking and practice. It is incumbent on all of us to determine whether a chronic pain patient has centralized or peripheral pain or both. A clinical diagnosis of centralized pain should now be entered into the medical record of all chronic pain patients. If the practitioner isn’t yet comfortable with his/her diagnostic understanding or assessment, use the term “presumed” or “suspected” centralized pain. Elevated inflammatory assays and abnormal serum hormone tests provide biologic markers to objectively help make a clinical diagnosis of centralized pain, as this condition is accompanied by neuroinflammation and hypothalamic-pituitary-adrenal stimulation. The permanency and serious consequences of centralized pain, particularly when undertreated and uncontrolled, can be tragic, as the central inflammatory process is associated with tissue destruction. Every practitioner needs to start evaluating every chronic pain patient for the presence of centralized pain, and a clinical diagnosis of centralized pain should be entered into the patient’s chart.