For example, in a patient with rheumatoid arthritis (RA), peripheral nociceptive input (in the form of inflammation) is likely the initial mechanism at work, but as time goes on, central processing becomes more involved. The patient may then begin to experience pain that is disproportionate to what is generally expected with RA and may develop other somatic symptoms. The diagnosis then becomes pain primarily related to RA with central sensitization, and both need to be addressed in a treatment plan. In rheumatic conditions, comorbid fibromyalgia (indicative of central sensitization) is thought to occur in 15% to 30% of patients.5
FPPs can utilize the underlying mechanisms to cut across diagnostic labels and tailor treatments to those that are most likely to be effective. For a patient with more prominent peripheral involvement, a procedural intervention such as injections or surgery alone may suffice, whereas a broader approach including psychotherapy, medications, exercise, and other lifestyle interventions may be necessary for a patient with pain caused predominantly by central sensitization.
Addressing both peripheral and central components is essential. One prospective, observational cohort study of more than 600 patients scheduled for unilateral total knee or total hip arthroplasty found that patients with a higher degree of centralization of pain (measured by widespread pain index and modified fibromyalgia screening scales) were less likely to report improvement in the affected body part and in overall body pain following surgery.6,7
There is a high degree of overlap among many of the chronic pain syndromes (fibromyalgia, irritable bowel syndrome, interstitial cystitis, chronic headaches) that have been found to have a central sensitization component.8 Providers of primary care are aptly positioned to recognize central sensitization as the underlying pathology and target treatment effectively.
TAILOR TREATMENT TO THE UNDERLYING MECHANISMS OF PAIN
As with any chronic condition, a thorough workup (complete with history, physical exam, and diagnostic testing, as appropriate) is indicated. In the setting of chronic pain, it’s important to identify the primary mechanism, as well as secondary factors that may contribute to the patient’s pain, before developing your treatment plan. These secondary factors may include co-occurring affect disorders, a history of trauma, poor sleep, and tobacco use.9-12 A history of trauma, for example, co-exists with many pain syndromes. For these patients, central sensitization is responsible for much of their pain. As a result, traditional cognitive behavioral therapy (CBT) may not be the best option because of its focus on accepting pain as a chronic diagnosis; more trauma-focused treatments, such as those dealing in emotional awareness and understanding of the CNS’s role in chronic pain, need to be considered.13
Three common conditions. Below we present evidence-based treatment approaches for conditions typically associated with each of the major mechanisms of chronic pain: fibromyalgia (central sensitization), OA (peripheral nociceptive), and low back pain (mixed pain state).
Fibromyalgia: a case of central sensitization
Fibromyalgia is a hallmark diagnosis for patients in whom central sensitization is the dominant cause of pain. They usually present with widespread, diffuse pain and somatic symptoms such as fatigue, memory difficulties, and poor sleep quality.8 When explaining the pain mechanism to patients, it may be useful to use the analogy of a volume control dial that is stuck in the “high” position and can’t be turned down.
Genes, the environment, and neurotransmitters play a role.The origin of the pain amplification process is believed to be multifactorial.
Genetic factors are thought to contribute to a predisposition for amplification. To date, five sets of genes have been implicated in increased sensitivity to pain leading to increased risk of the development of chronic pain during a patient’s lifetime.14-19
Environmental factors (eg, early life trauma, physical trauma especially to the trunk, certain infections such as Lyme disease and Epstein-Barr virus, and emotional stress) may trigger or exacerbate symptoms.8 Of note: Only about 5% to 10% of people who experience these triggers actually develop a chronic pain state, while the rest regain their baseline health.4 This raises the question of whether there is a point during an acute pain episode in which one can intervene and prevent the acute pain from becoming chronic in those at higher risk.4
Imbalances of neurotransmitters (high glutamate; low norepinephrine, serotonin, and gamma-aminobutyric acid [GABA]) play a role in central amplification.20-22 These substances not only affect sensory transmission, but also control levels of alertness, sleep, mood, and memory.
The diagnostic criteria for fibromyalgia were modified in 2011 to remove the tender point examination and to add somatic symptoms.6 These criteria can be useful in the clinical setting in identifying not only fibromyalgia itself but also the degree of “fibromyalgianess” a patient has, which is an indicator of how large a role the centralization process plays in the maintenance of chronic pain.23,24
Treatment: multimodal and patient empowering. Evidence-based treatment options for fibromyalgia, as well as other conditions for which there is a high degree of centralized pain, can be found in Table 2.25-36 Multimodal treatment, with an emphasis on patient knowledge and empowerment, is generally thought to be the most beneficial.25,37 Treatment should almost always include CBT and exercise/activity therapies, which have high degrees of efficacy with few adverse effects.26,29
In terms of medication, centrally-acting agents (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors [SNRIs], and alpha 2 delta ligands) are the most effective. There is little to no data showing benefit from anti-inflammatories or opioids in the setting of fibromyalgia. There is some data to suggest that combination therapy, for example with an SNRI (milnacipran) and an alpha 2 delta ligand (pregabalin), may provide more benefit than treating with pregabalin alone.38
Complementary and alternative therapies (eg, yoga, chiropractic care, acupuncture, massage) are being studied more, and while evidence is only preliminary in terms of efficacy, there is increasing emphasis being placed on the need for patients with chronic pain to shift their treatment expectations to greater acceptance of pain and the need for ongoing self-care.28
