Thus, plasma and/or serum levels of proinflammatory cytokines IL-6 and IL-8 are elevated in patients with FM, as were cerebrospinal fluid (CSF) levels of IL-8 in one study. Indeed, the CSF is a relevant body fluid to investigate in pain conditions, as it is in direct contact with the CNS and can be hypothesized to mirror CNS pathology. CSF levels of classical neuropeptides such as substance P, beta-endorphin and other endogenous opioids have therefore been studied in many different pain states.
In the Journal of Pain Research study, Emmanuel Bäckryd and colleagues from the Pain and Rehabilitation Center, Linköping University, Sweden investigated the CSF and plasma inflammatory profiles of FM patients compared with healthy controls.
Instead of analyzing only a few substances at a time, the investigators applied the multiplex proximity extension assay (PEA) in which 92 proteins were simultaneously analyzed in cerebrospinal fluid (CSF) and plasma samples from 40 FM patients. They determined the CSF and plasma inflammatory profiles of 40 FM patients compared to healthy controls (CSF) and blood donors (plasma).
The authors found elevated IL-8 levels in both CSF and plasma FM samples, confirming previous reports, whereas high levels of CX3CL1 were monitored only in CSF samples. As per the authors, this may indicate the presence of both neuroinflammation and chronic systemic inflammation in FM.
Regarding the question of causality, the authors discuss and hypothesize 3 major scenarios: 1) their results reflect the involvement of these chemokines in the pathophysiology of FM; 2) they reflect a risk factor present prior to the development of chronic pain, and 3) they may indicate just a consequence of the chronic pain condition, and “mirroring pain-related stress, inactivity, depression or bad sleep”.
Disentangling the contribution of these potentially mutually interacting factors will be very difficult. For instance, levels of peripheral IL-6 are known to be influenced by regular exercise, individuals who are inactive having higher baseline levels of this particular cytokine.