Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

Abstract

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n ¼ 26), CSF CRF levels were associated with sensory pain symptoms (r ¼ 0.574, p ¼ 0.003) and affective pain symptoms (r ¼ 0.497, p ¼ 0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t ¼ 2.54, p ¼ 0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

“…One study showed that CRH was elevated in CSF of FMS patients and was associated with pain but not fatigue symptoms (McLean et al, 2006). The increased serum CRH reported in the current study may indicate some level of physical or psychologic stress that may exacerbate FMS symptoms (Geenen et al, 2002;Fischer et al, 2016).…”

A six‐month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia

“…We speculate that these improvements may be related to an augmentation of parasympathetic tone as a consequence of the daily use of PYD (28) and regular exercise (29). There is now persuasive evidence that FM patients have dysautonomia, as evidenced by results of heart rate variability studies, tilt-table testing (30), and sympathetic skin responses (31)(32)(33)(34). Two common clinical manifestations of dysautonomia are neurally mediated hypotension and postural orthostatic tachycardia syndrome (35,36).…”

Fibromyalgia Syndrome in Need of Effective Treatments

“…The normal circadian rhythm for plasma cortisol level is disrupted in FMS patients as evidenced by elevated plasma concentrations in the evening . Corticotropin-releasing hormone (CRH), the principal central nervous system mediator of the stress response, was elevated in the cerebrospinal fluid (CSF) of FMS patients and was associated with pain but not fatigue symptoms (McLean et al, 2006). FMS is quite common in patients with systemic mastocytosis (Theoharides et al, 2015b), a disorder characterized by a higher number and reactivity of mast cells (MCs) (Theoharides et al, 2015c).…”