Proteomic Analysis to Identify Prospective Biomarkers of Treatment Outcome After Microvascular Decompression for Trigeminal Neuralgia: A Preliminary Study.

Trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder, often caused by vascular or neuronal compression of the trigeminal nerve. In such cases, microvascular decompression (MVD) surgery can be used to treat TN, but pain relief is not guaranteed. The molecular mechanisms that affect treatment response to MVD are not well understood. In this exploratory study, we performed label-free quantitative proteomic profiling of plasma and cerebrospinal fluid samples from patients undergoing MVD for TN, then compared the proteomic profiles of patients graded as responders (n = 7) versus non-responders (n = 9). We quantified 1,090 proteins in plasma and 1,087 proteins in the cerebrospinal fluid, of which 12 were differentially regulated in the same direction in both sample types. Functional analyses of differentially regulated proteins in protein-protein interaction networks suggested pathways of the immune system, axon guidance, and cellular stress response to be associated with response to MVD. These findings suggest potential biomarkers of response to MVD, as well as possible mechanisms of variable treatment success in TN patients. PERSPECTIVE: This exploratory study evaluates proteomic profiles in plasma and cerebrospinal fluid of patients undergoing microvascular decompression surgery for trigeminal neuralgia. Differential expression of proteins between surgery responders versus non-responders may serve as biomarkers to predict surgical success and provide insight into surgical mechanisms of pain relief in trigeminal neuralgia.

Evidence-based consensus guidelines on patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain.

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

Chronic pain and infection: mechanisms, causes, conditions, treatments, and controversies.

Throughout human history, infection has been the leading cause of morbidity and mortality, with pain being one of the cardinal warning signs. However, in a substantial percentage of cases, pain can persist after resolution of acute illness, manifesting as neuropathic, nociplastic (eg, fibromyalgia, irritable bowel syndrome), or nociceptive pain. Mechanisms by which acute infectious pain becomes chronic are variable and can include immunological phenomena (eg, bystander activation, molecular mimicry), direct microbe invasion, central sensitization from physical or psychological triggers, and complications from treatment. Microbes resulting in a high incidence of chronic pain include bacteria such as the Borrelia species and Mycobacterium leprae, as well as viruses such as HIV, SARS-CoV-2 and herpeses. Emerging evidence also supports an infectious cause in a subset of patients with discogenic low back pain and inflammatory bowel disease. Although antimicrobial treatment might have a role in treating chronic pain states that involve active infectious inflammatory processes, their use in chronic pain conditions resulting from autoimmune mechanisms, central sensitization and irrevocable tissue (eg, arthropathy, vasculitis) or nerve injury, are likely to cause more harm than benefit. This review focuses on the relation between infection and chronic pain, with an emphasis on common viral and bacterial causes.

Multicenter study evaluating factors associated with treatment outcome for low back pain injections.

BACKGROUND: There has been a worldwide surge in interventional procedures for low back pain (LBP), with studies yielding mixed results. These data support the need for identifying outcome predictors based on unique characteristics in a pragmatic setting. METHODS: We prospectively evaluated the association between over two dozen demographic, clinical and technical factors on treatment outcomes for three procedures: epidural steroid injections (ESIs) for sciatica, and sacroiliac joint (SIJ) injections and facet interventions for axial LBP. The primary outcome was change in patient-reported average pain intensity on a numerical rating scale (average NRS-PI) using linear regression. For SIJ injections and facet radiofrequency ablation, this was average LBP score at 1 and 3 months postprocedure, respectively. For ESI, it was average leg pain 1- month postinjection. Secondary outcomes included a binary indicator of treatment response (success). RESULTS: 346 patients were enrolled at seven hospitals. All groups experienced a decrease in average NRS-PI (p<0.0001; mean 1.8±2.6). There were no differences in change in average NRS-PI among procedural groups (p=0.50). Lower baseline pain score (adjusted coefficient -0.32, 95% CI -0.48 to -0.16, p<0.0001), depressive symptomatology (adjusted coefficient 0.076, 95% CI 0.039 to 0.113, p<0.0001) and obesity (adjusted coefficient 0.62, 95% CI 0.038 to 1.21, p=0.037) were associated with smaller pain reductions. For procedural outcome, depression (adjusted OR 0.94, 95% CI 0.91, 0.97, p<0.0001) and poorer baseline function (adjusted OR 0.59, 95% CI 0.36, 0.96, p=0.034) were associated with failure. Smoking, sleep dysfunction and non-organic signs were associated with negative outcomes in univariate but not multivariate analyses. CONCLUSIONS: Identifying treatment responders is a critical endeavor for the viability of procedures in LBP. Patients with greater disease burden, depression and obesity are more likely to fail interventions. Steps to address these should be considered before or concurrent with procedures as considerations dictate. TRIAL REGISTRATION NUMBER: NCT02329951.

Waddell (Nonorganic) Signs and Their Association With Interventional Treatment Outcomes for Low Back Pain.

BACKGROUND: The rising use of injections to treat low back pain (LBP) has led to efforts to improve selection. Nonorganic (Waddell) signs have been shown to portend treatment failure for surgery and other therapies but have not been studied for minimally invasive interventions. METHODS: We prospectively evaluated the association between Waddell signs and treatment outcome in 3 cohorts: epidural steroid injections (ESI) for leg pain and sacroiliac joint (SIJ) injections and facet interventions for LBP. Categories of Waddell signs included nonanatomic tenderness, pain during sham stimulation, discrepancy in physical examination, overreaction, and regional disturbances divulging from neuroanatomy. The primary outcome was change in patient-reported "average" numerical rating scale for pain intensity (average NRS-PI), modeled as a function of the number of Waddell signs using simple linear regression. Secondary outcomes included a binary indicator of treatment response. We conducted secondary and sensitivity analyses to account for potential confounders. RESULTS: We enrolled 318 patients: 152 in the ESI cohort, 102 in the facet cohort, and 64 in the SIJ cohort, having sufficient data for primary analysis on 308 patients. Among these, 62% (n = 192) had no Waddell signs, 18% (n = 54) had 1 sign, 11% (n = 33) had 2, 5% (n = 16) had 3, 2% (n = 7) had 4, and about 2% (n = 6) had all 5 signs. The mean change in average NRS-PI in each of these 6 groups was -1.6 ± 2.6, -1.1 ± 2.7, -1.5 ± 2.5, -1.6 ± 2.6, -1 ± 1.5, and 0.7 ± 2.1, respectively, and their corresponding treatment failure rates were 54% (102 of 192), 67% (36 of 54), 70% (23 of 33), 75% (12 of 16), 71% (5 of 7), and 83% (5 of 6). In the primary analysis, an increasing number of Waddell signs were not associated with a significant decrease in average NRS-PI (coefficient [Coef] = 0.19; 95% confidence interval [CI], -0.43 to 0.05; P = .12). A higher number of Waddell signs were associated with treatment failure, with a 1.35 increased odds of treatment failure per cumulative number of signs (P = .008). CONCLUSIONS: Whereas this study found no consistent relationship between Waddell signs and decreased mean pain scores, a significant relationship between the number of Waddell signs and treatment failure was observed.