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13 Articles in Volume 18, Issue #6
Authorities’ Use of Big Data May Harm—or Help—Your Chances of Investigation
Gaps in the Pharmacist’s Pain Management Role
How can cyproheptadine manage complicated chronic pain cases?
Letters to the Editor: Trackable Pills; Buprenorphine; CRPS Diagnosis
Managing a New High-Dose Opioid Patient
Managing Opioid Use Disorder
Medication Selection for Comorbid Pain Management (Part 2)
Mobile Trackers and Digital Therapeutics
New Insights in Understanding Chronic, Central Pain
Nocebo Effects: How to Prevent them in Patients
Polarizing Topics in Chronic Pain
The Fight to End Peripheral Neuropathy
Urine Drug Monitoring

New Insights in Understanding Chronic, Central Pain

A review of recent research advances—coupled with case illustrations—offers a guide for better recognizing non-cancer-related centralized pain.
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During the past few years, there have been significant breakthroughs in the medical community’s understanding of chronic, non-cancer-related central pain. In addition to reviewing the updated terminology and classification of central pain, this paper examines recent studies that have elucidated the mechanisms involved in central pain, initially using fibromyalgia as the prototypic illness. The role of central pain in a variety of other chronic painful conditions, as well as in systemic, rheumatic diseases, are also explored using case illustrations.

Updated Terminology and Classification

Chronic pain has been traditionally defined as lasting more than 3 months or lasting beyond that expected following normal healing. It affects hundreds of millions of people, estimated at one-third of the world’s population at any single time. Until about the year 2000, “chronic pain” was attributed to an ongoing peripheral noxious stimulus, usually classified as inflammatory, neurogenic, or structural in nature. “Central pain” was a term used to describe idiopathic, chronic pain following a brain injury.

Research by Clifford Woolf and colleagues demonstrated that chronic pain may be explained by aberrant central nervous system pain processing, hence the term “central” or “centralized” pain.1 Today, central pain is characterized by hyperalgesia, an increased response to a noxious stimulus, and allodynia, a painful response to a stimulus considered to be non-noxious. This categorization has been broadened to include any chronic pain not conforming to peripheral, nociceptive pathways and is considered one of four chronic pain categories, which also include inflammatory, structural, and neurogenic (see Figure 1).

However, it has become increasingly clear that subdividing chronic pain into these four categories may be misleading since central pain is an important contributor to inflammatory, structural, and neurogenic pain. Pain categories are fluid and may change over time in a single individual, as described in the patient examples herein.

In an attempt to develop an evidence-based taxonomy for chronic pain disorders, the Analgesic, Anesthetic, and Addiction Clinical Trials Translations Innovations Opportunities and Networks (ACTTION) redefined chronic pain conditions in 2014 according to their proposed biopsychological mechanisms: peripheral, musculoskeletal, orofacial, visceral, and unclassified (see Table I).2 The initial organization of these chronic pain categories known as the ACTTION-American Pain Society Pain Taxonomy (AAPT) has provided a framework for various pain specialists to come to a consensus regarding chronic pain classifications.

“Central pain,” also called “central sensitivity” or “centralized pain,” is therefore the term now used to encompass any condition wherein pain is generated from the central, rather than the peripheral, nervous system. This type of pain may be the primary source of pain, as in the classic central pain disorders, fibromyalgia syndrome, irritable bowel syndrome, tension-type chronic headaches, temporomandibular joint syndrome, and chronic pelvic/bladder pain syndromes.

Central pain is also considered to be dysfunctional, which to some clinicians implies psychogenic. The clinical phenotype includes generalized pain, fatigue, sleep and mood disturbances. Central pain may also be associated with depression, catastrophizing, and other psychological states but is not considered a psychiatric illness.

Fibromyalgia: A Prototype for Central Pain Patient Example

A 48-year-old female complains of generalized musculoskeletal (MSK) pain on a daily basis for more than 5 years. The pain has not been associated with any joint swelling or inflammation and she describes that, “It feels as if I always have the flu.” She also has persistent fatigue and does not sleep well, often awaking in pain. She never feels refreshed in the morning. Her past medical history includes long-standing tension-type headaches and a bout of depression shortly after delivering her first child 15 years ago. Currently, she reports no mood disturbances although admits feeling increasingly frustrated about her lack of well being.

On examination there is no obvious joint swelling or inflammation and no sign of joint deformities. The general neurologic evaluation is unremarkable. She is quite tender with modest pressure around soft tissue areas including over the neck, shoulders, outer hips, and the chest wall. There were no other physical abnormalities. Laboratory studies included a normal complete blood count, a normal chemistry profile, normal thyroid function tests, and a normal erythrocyte sedimentation rate (ESR).

This patient meets the criteria for fibromyalgia.3 She has more than five years of widespread MSK pain associated with fatigue and sleep disturbance. There is no evidence of joint inflammation or an underlying systemic arthritis or a systemic connective tissue disease. Basic laboratory tests, including ESR, are unremarkable.

Review & Discussion

Fibromyalgia is the most common form of unexplained widespread MSK pain, affecting 2 to 6% of the global population. Chronic widespread pain not related to a specific structural disease, is even more common, affecting 5 to 15% of the population. There is no clear boundary separating chronic widespread pain from fibromyalgia.

Thus, fibromyalgia offers a clear clinical prototype for central pain and has been the model condition in research attempting to elucidate the pathophysiologic mechanisms of centralized pain for decades.3,4 Although there is no single, reproducible polymorphism or haplotype associated with fibromyalgia, a number of studies have found modest genetic influences.

The odds ratio of developing fibromyalgia is 8-fold greater in a relative of a person with fibromyalgia than a relative of a person with rheumatoid arthritis.5 Polymorphisms in genes associated with pain sensitivity, including catechol-O-methyltransferase (COMT), the serotonin transporter gene (5-HTTLPR), adrenergic-receptor genes and mu-opioid genes, have been noted in fibromyalgia, although the strongest evidence has been from genome-wide linkage data.6 Interactions of mu-opioid receptor and serotonergic genes were found to modify pain sensitivity in fibromyalgia patients.7

Last updated on: October 5, 2018
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Classic Central Pain Syndromes: Review of Neurologic Causes of Pain