Introduction:
Spinal stenosis, causing nerve root compression, is a common factor for neuropathic pain. While many patients undergo spinal surgery for relief, some patients continue to experience neuropathic pain even after successful surgery. Research has focused on identifying and addressing the molecular causes of neuropathic pain, with several biomarkers implicated, though the exact mechanisms remain unclear. In this study, we analyzed the biomarkers in the cerebrospinal fluid (CSF) to identify factors that contribute not only to neuropathic pain but also to persistent neuropathic pain after lumbar surgery.
Materials and Methods:
CSF samples were gathered from patients who had a dural tear injury during surgery or who underwent myelography, from July 2022 to July 2023. Exclusion criterias were those with infections, tumors, trauma, previous spine surgeries, or additional surgeries post-initial operation. Patients were evaluated for pain and neuropathic pain using LANSS, PDQ, DN4, ODI, and NRS questionnaires preoperatively, and at 1 month, 3 months, and 1 year postoperatively, and divided into three groups based on the presence of neuropathic pain. CSF samples were processed and analyzed using ELISA to measure various biomarkers.
Results:
A total of 32 CSF samples were collected, with 10 patients excluded due to insufficient follow-up or refusal to complete questionnaires. Among the remaining 22 patients, 16 had preoperative neuropathic pain. Of these, 8 had resolved pain postoperatively, while 8 had persistent pain. Patients were categorized into Group A (no neuropathic pain), Group B (resolved neuropathic pain), and Group C (persistent neuropathic pain).
Comparisons revealed significant differences in IL-6 between groups B and C (B=4.81±3.8, C=1.58±1.57, p=0.028), and between groups A and C for both IL-6 (A=6.18±5.07, C=1.58±1.57, p=0.031) and MCP1 (A=1.19±0.73, C=0.6±0.08, p=0.05), but no significant differences between groups A and B. Moderate correlations were found between biomarkers and NP improvement post-surgery (Spearman's rho: 0.56, p=0.024; Kendall’s tau: 0.48, p=0.03). However, IL-6 levels did not correlate with NRS scores for back and leg pain, or ODI scores one year postoperatively. The ODI score difference pre- and post-surgery also showed no significant correlation with IL-6 levels.
Discussion:
In our study, biomarkers that have been reported to have relevance to neuropathic pain such as IL-6, were not positively related to persistent neuropathic pain. Rather, patients with higher levels of IL-6 and other biomarkers had no neuropathic pain or resolved neuropathic pain. It can be implied that mechanism of chronic neuropathic pain is different from acute neuropathic pain. Further studies are needed to identify the exact mechanisms for chronic and persistent neuropathic pain. The limitation of our study was the small size and volume of CSF samples.
Conclusions:
Interleukin-6 concentration was significantly lower in patients with persisting neuropathic pain after the surgery. Other biomarkers such as Her1 and MCP-1 showed similarly lower in patients with persistent neuropathic pain. It can be suggested that biomarkers associated with neuropathic pain primarily impact the acute phase, while persistent neuropathic pain requires distinct consideration and treatment approaches.