Chronic widespread (centralized) pain (or nociplastic pain) is pain that persists or recurs for > 3 months, persists > 1 month after resolution of an acute tissue injury, or accompanies a nonhealing lesion. Causes include chronic disorders (eg, cancer, arthritis, diabetes), injuries (eg, herniated disk, torn ligament), and many primary pain disorders (eg, neuropathic pain, fibromyalgia, chronic headache). Various medications and psychological treatments are used.
(See also Fibromyalgia and Overview of Pain.)
Unresolved, long-lasting pain disorders may be classified by etiology (eg, cancer, rheumatoid arthritis, herniated disk) or by pathophysiologic mechanism (eg, nociceptive, neuropathic, nociplastic). Most chronic pain conditions likely represent a mixed state. For example, a peripheral nerve injury causing neuropathic pain may result in changes in the CNS causing nociplastic pain. Alternatively, injury, even if mild, may lead to long-lasting changes (sensitization) in the nervous system—from peripheral receptors to the cerebral cortex—that may produce persistent pain in the absence of ongoing nociceptive stimuli. With sensitization and nociplastic pain, discomfort due to a nearly resolved disorder that might otherwise be perceived as mild or trivial is instead perceived as significant pain.
In some cases (eg, chronic back pain after injury), the original precipitant of pain is obvious; in others (eg, chronic headache, atypical facial pain, chronic abdominal pain), the precipitant is remote or occult. In most chronic pain conditions, however, it is hard to discern evidence of ongoing damage or injury, or to identify a clear remedy.
Chronic pain can precipitate psychological distress, but preexisting psychological factors can significantly influence the overall pain experience. Chronic pain commonly leads to or exacerbates psychological problems (eg, depression, anxiety). Distinguishing psychological cause from effect is often difficult.
People (eg, family members, friends) and various other factors in the patient’s environment may reinforce behaviors that perpetuate chronic pain. Certain risk factors, including adverse childhood events (physical, emotional, verbal, and sexual abuse), have been shown to increase the risk of developing chronic pain in adulthood.
Fibromyalgia
Fibromyalgia is among the most common chronic widespread pain syndromes and is a representative example of a nociplastic pain condition. Like most chronic pain syndromes, it is more common among women; however, when the diagnostic criteria were updated in 2016, more men are now being diagnosed with fibromyalgia than in the past and the gender gap has decreased.
The pathophysiology is unknown, but a central sensitization syndrome with impairment of pain regulation may be involved, and the nociceptive pathways and processing centers are primed and overreactive to stimuli.
The diagnosis is clinical, and there are no confirmatory diagnostic tests. However, several organizations have developed specific diagnostic criteria (1, 2). Diagnostic criteria include a widespread pain index (WPI), which accounts for a more widespread distribution of chronic pain, as well as a symptom severity (SS) score, which accounts for symptoms such as fatigue, cognitive impairment, sleep disturbances, and gastrointestinal symptoms; some of these symptoms are referred to by patients as "fibro fog." It is these later, non-pain symptoms that distinguish chronic widespread pain from nociplastic phenotypes.
Fibromyalgia references
1. Galvez-Sánchez CM, A. Reyes del Paso GA. Diagnostic criteria for fibromyalgia: Critical review and future perspectives. J Clin Med. 9 (4): 1219, 2020. doi: 10.3390/jcm9041219
2. Häuser W, Brähler E, Ablin J, Wolfe F. Modified 2016 American College of Rheumatology fibromyalgia criteria, the analgesic, anesthetic, and addiction clinical trial translations innovations opportunities and networks–American Pain Society Pain Taxonomy, and the Prevalence of Fibromyalgia. Arthritis Care & Research. 73 (5): 617–625, 2021.
Treatment of Chronic Widespread (Centralized) Pain
Often multimodal therapy (eg, analgesics, physical methods, psychological treatments, interventional management techniques)
Treatment strategies for fibromyalgia can be used as a template for the treatment of many nociplastic pain disorders or components of nociplastic pain in chronic pain conditions. The foundation of treatment is multimodal therapy (eg, analgesics, physical therapy, psychological treatments, and self-management).
Medications
Analgesics used for chronic widespread pain include
Gabapentin or pregabalinGabapentin or pregabalin
Serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, milnacipran)Serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, milnacipran)
Tricyclic antidepressants (eg, nortriptyline, amitriptyline, desipramine)Tricyclic antidepressants (eg, nortriptyline, amitriptyline, desipramine)
Low-dose naltrexoneLow-dose naltrexone (LDN) is used as an off-label treatment for fibromyalgia, leveraging its ability to modulate the immune system and reduce inflammation, which may help alleviate pain and fatigue. LDN is thought to work by temporarily blocking opioid receptors, leading to a rebound increase in endorphin production, which can enhance pain relief and improve mood. While research on LDN for fibromyalgia is still emerging, some studies suggest it may be an effective and well-tolerated option for managing symptoms in certain patients (1).
Use of one or more medications with different mechanisms of action (rational polypharmacy) is often necessary.
Nonpharmacologic treatments
Physical therapy, in particular, low-impact aerobic exercise, is beneficial for nociplastic pain and forms the cornerstone of the current treatment paradigm for fibromyalgia (2). Physical therapy for fibromyalgia typically focuses on improving physical function and reducing pain through tailored exercise programs that include stretching, strengthening, and low-impact aerobic activities. Therapists may also incorporate techniques such as manual therapy, hydrotherapy, and education on pain management strategies to enhance patients' ability to manage symptoms. Increasing physical activity and exercise is crucial for patients with fibromyalgia, as it can improve physical function, sleep, pain, and fatigue. Exercise programs should be individualized based on patient preferences, physical status, and comorbidities, with an emphasis on low-impact aerobic activities and gradual progression. Although patients may experience initial discomfort, setting realistic expectations and pacing can enhance adherence and long-term benefits, with strong evidence supporting the efficacy of activities like low-impact aerobic exercise, strength training, and tai chi (3).
Patient education for nociplastic pain is essential and should include a discussion about the noninflammatory nature of the condition, the limited but helpful effects of pharmacologic therapy, and the importance of a multimodal treatment approach. Clinicians should emphasize the management of comorbid conditions, educate patients on sleep hygiene, and direct them to reliable resources. Studies support that patient education, especially when combined with other nonpharmacologic strategies, can significantly improve symptoms and overall patient outcomes (4).
Pain psychology, including behavioral therapy can improve patient function, even without reducing pain. Patients should keep a diary of daily activities to pinpoint areas amenable to change. The physician should make specific recommendations for gradually increasing physical activity and social engagement. Activities should be prescribed in gradually increasing units of time; pain should not, if at all possible, be allowed to abort the commitment to greater function. When activities are increased in this way, reports of pain often decrease.
Cognitive or psychological therapies, such as cognitive-behavioral therapy (CBT), mindfulness-based stress reduction, and relaxation techniques, are recommended for most patients with nociplastic pain and should be tailored to individual preferences and resource availability. These therapies, particularly CBT, have been supported by evidence for improving physical function, pain, and mood, with emerging digital options increasing accessibility for patients.
Behavior of family members or fellow workers that reinforces pain behavior (eg, constant inquiries about the patient’s health or insistence that the patient do no chores) should be discouraged. The physician should avoid reinforcing pain behavior, discourage maladaptive behaviors, applaud progress, and provide pain treatment while emphasizing return of function.
Pain rehabilitation programs are multidisciplinary programs for patients with chronic pain. These programs include education, cognitive-behavioral therapy, physical therapy, medication regimen simplification, and sometimes detoxification and tapering of analgesics. They focus on
Restoring function
Improving quality of life
Helping patients control their own life, despite chronic pain
Interventional pain management includes various minimally invasive procedures that may help treat widespread pain by targeting the possible source of that pain.
Treatment references
1. Patten DK, Schultz BG, Berlau DJ. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. . The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.Pharmacotherapy. 2018;38(3):382-389. doi:10.1002/phar.2086
2. Arribas-Romano A, Fernández-Carnero J, Molina-Rueda F, Angulo-Diaz-Parreño S, Navarro-Santana MJ. Efficacy of Physical Therapy on Nociceptive Pain Processing Alterations in Patients with Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis. Pain Med. 2020;21(10):2502-2517. doi:10.1093/pm/pnz366
3. Bidonde J, Busch AJ, Schachter CL, et al. Aerobic exercise training for adults with fibromyalgia. Cochrane Database Syst Rev. 2017;6(6):CD012700. Published 2017 Jun 21. doi:10.1002/14651858.CD012700
4. Saracoglu I, Akin E, Aydin Dincer GB. Efficacy of adding pain neuroscience education to a multimodal treatment in fibromyalgia: A systematic review and meta-analysis. Int J Rheum Dis. 2022;25(4):394-404. doi:10.1111/1756-185X.14293
