Cerebrospinal fluid levels of glial cell-derived neurotrophic factor correlate with spinal cord stimulation frequency in patients with neuropathic pain: a preliminary report

Abstract

Study design: Case series. Objectives: To evaluate relationships between spinal cord stimulation (SCS) parameters and levels of glial cell-derived neurotrophic factor (GDNF). Setting: Ambulatory pain clinic of St James's Hospital, Dublin, Ireland. Methods: Nine patients with an implanted SCS and Failed Back Surgery Syndrome (FBSS) were administered the Brief Pain Inventory and Short Form (36) Health Survey. Following a lumbar puncture, levels of GDNF in cerebrospinal fluid (CSF) were assayed and correlated with stimulation parameters. Controls were patients with arthritic back pain who were matched for age, gender and SF-36 score. Results: Concentrations of GDNF in CSF are higher in patients with FBSS than controls (P ¼ 0.002) and correlate with SCS frequency (P ¼ 0.029). Conclusion: Concentrations of GDNF in CSF are higher in neuropathic pain and appear to be related to stimulation frequency. Further work is needed to evaluate this potential relationship, both in neuropathic pain and in other contexts such as locomotor dysfunction.

Burst Spinal Cord Stimulation Increases Peripheral Antineuroinflammatory Interleukin 10 Levels in Failed Back Surgery Syndrome Patients With Predominant Back Pain

“…Contrary to the results of the blood analysis in our study, other preclinical and human studies investigating the correlation between neuroinflammation and back pain measured cytokine concentrations in cerebrospinal fluid (CSF), a biofluid compartment closer to the neural interface. In particular, the methodologies used to determine TNF-a values vary, and while some studies demonstrate enhanced plasma levels by LPS-induction, our ELISA protocol failed to sufficiently assess TNF-a (8,9). Furthermore, while elevation of IL-1b has been reported in FBSS patients with predominant neuropathic leg pain, this was not the case in our VAS B dominant FBSS subgroup.…”

“…In accordance with earlier observations, significantly higher GDNF values were present in patients with FBSS compared to those of healthy controls. Furthermore, a correlation was found between SCS frequency and CSF-GDNF levels (9).…”

“…Human and preclinical model studies have observed a possible correlation between the back pain of intervertebral disc degeneration and pro-/anti-inflammatory mediators in different bio-fluids (CSF/blood) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

“…There is accumulating clinical and experimental evidence confirming the existence of potent, adaptive interactions between the central and peripheral aspects of the Neuro-immune System in the genesis and maintenance of chronic neuropathic and nociceptive back pain (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The neuro-inflammatory pathway is modulated by the interaction of pro-and anti-inflammatory cytokines and chemokines, and peripheral immune system-derived cells (macrophages, leukocytes).…”

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

“…To explain their results, authors have hypothesized that a major component of blood GDNF comes from sources other than CNS, as GDNF does not cross the blood brain barrier (BBB). Finally, in another recent preliminary report the CSF levels of GDNF were seen to be higher in patients suffering from neuropathic pain when compared with those of patients suffering from arthritic back pain [71]. These observations are more difficult to be grouped in a coherent frame encompassing a clear relationship of GDNF and pain.…”