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16 Articles in Volume 19, Issue #2
Analgesics of the Future: Inside the Potential of Glial Cell Modulators
APPs as Leaders in Pain Management
Cases in Urine Drug Monitoring Interpretation: How to Stay in Control
Complex Chronic Pain Disorders
Efficacy of Chiropractic Care for Back Pain: A Clinical Summary
Hydrodissection for the Treatment of Abdominal Pain Caused by Post-Operative Adhesions
Letters: The Word "Catastrophizing;" AIPM Ceases Operations; Patient Questions
Management of Severe Radiculopathy in a Pregnant Patient
Managing Pain in Adults with Intellectual Disabilities
Pain in the Courtroom: An Excerpt
Q&A with Howard L. Fields: How Patients’ Expectations May Control Pain
Special Report: CGRP Monoclonal Antibodies for Chronic Migraine
The Management of Chronic Overlapping Pain Conditions
Vibration for Chronic Pain
What are the dangers of loperamide abuse?
When Patient Education Fails to Improve Outcomes: A Low Back Pain Case

Complex Chronic Pain Disorders

The pathophysiology of and approaches to 3 commonly seen pain conditions: CRPS, EDS, and SFN.
Pages 26-32
Page 4 of 4

Furthermore, decreased IENF density may be a disease epiphenomenon rather than causal. Abnormal IENF density has not correlated well with neuropathic symptom severity or outcomes. Decreased IENF density has been found in other chronic pain disorders and in conditions not typically associated with pain, such as amyotrophic lateral sclerosis. IENF loss was present in 70% of patients with amyotrophic lateral sclerosis (ALS) and did not correlate with disease onset, phenotype, symptoms, or severity.33 Is small fiber pathology responsible for chronic pain, or a result of chronic pain? This question was addressed in a rodent experimental model in which increasing levels of glutamate in the insula, a characteristic of neuroimaging findings in fibromyalgia, correlated with increased pain behavior and decreased peripheral nerve fibers.34


The first step in the treatment of SFN is to identify and treat any underlying disease (see Table X). Extrapolating from treating other neuropathic diseases, optimal management of associated diseases such as diabetes mellitus, HIV infection, or systemic, immune disorders should help to prevent the progression of SFN. There have been no controlled studies on medications in the treatment of SFN associated with a systemic disease. In one report, SFN was present in 143 patients with sarcoidosis.35 The majority of these patients responded either to intravenous immunoglobulin or anti-TNF medication, or a combination of both.

In the only randomized clinical trial of SFN, 18 patients were treated with gabapentin, tramadol, or diphenhydramine,36 where both gabapentin and tramadol provided significant pain reduction in comparison to diphenhydramine. It is advised that treatment for SFN conform to the recommended guidelines for managing general neuropathic pain.37 First-line agents typically include tricyclic antidepressants (particularly amitriptyline), anticonvulsants such as gabapentin and pregabalin, and the dual reuptake inhibitor duloxetine; the anticonvulsant lacosamide has been used in a proof of principle SFN report and in patients with sodium-channel genetic mutation causing SFN.38 Topical lidocaine may be used for focal neuropathic pain. Most guidelines reserve tramadol as a second-line agent and recommend limiting the use of opioids.37 OnabotulinumtoxinA, capsaicin, topical anesthetics, and analgesics have shown benefit in small series as have nerve root injections, transcutaneous electrical nerve stimulation, acupuncture, and tissue massage.


Complex regional pain syndrome, Ehlers-Danlos syndrome, and small fiber neuropathy represent common, chronic pain conditions with poorly understood pathophysiology. They are often difficult to diagnose and to treat as pathophysiologic mechanisms of these disorders involve both peripheral and central pain mechanisms. As such, they cannot be easily pigeonholed as neurologic, inflammatory, or immune diseases. Until these diseases are better understood, treatment may be similar, focused on multidisciplinary pain management with judicious use of similar medications.

Last updated on: March 4, 2019
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