Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

A relatively small scale, but very interesting study looking at the pathophysiology of fibromalgia (FM). FM is characterized by chronic widespread pain and increased pain sensitivity, with a global incidence of 2% (more common in females). Systemic and neuro-inflammatory mechansims are presumed to be important in FM, but analysis of cytokines in CSF or plasma of FM patients has been extremely limited. The authors used the INF I panel to widen the search for inflammatory proteins that may shed more light on this disease. For the CSF study, 40 female FM patients and 11 healthy controls (64% female) were compared, and 53 INF proteins that passed the study criteria were used for analysis. 11 markers (chemokines, cytokines and pro-inflammatory growth factors) were identified that highly discriminated between FM and control groups (Figure 1 in the paper is a nice visual example of stratification). In the plasma analysis, 35 FM patients and 47 blood donor controls were used, and 75 proteins passed the study criteria. 21 of the markers analyzed were highly discriminatory for FM, and four of these overlapped with the results from CSF: CXCL6, LAPTGF-beta-1, CXCL5 and MCP-2. This overlap is in keeping with the idea that plasma and CSF mirror different biological compartments, but that they are also interlinked. The high proportion of CC/CXL chemokines that associate with FM in CSF is in line with other lines of evidence that suggest an important role for neuroimmunity in chronic pain (chemokines are released by neural cells in response to injury and activate cytokines to trigger neuroinflammation). CX3CL1, which was identified in the CSF “profile” in this study, has been proposed as one of the principle signaling pathways in preclinical models of neuropathic pain. They conclude that this “holistic” inflammatory profiling of CSF & plasma in FM patients has provided important pathophysiological insights into the disease. Moreover, the persisting idea that FM may be “spontaneous” or even psychological in origin can now be challenged with objective biochemical changes.