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Background: Although integrated traditional Chinese medicine (TCM) has long been indicated to be effective in the treatment of sciatica and is widely used in the management of this condition, the mechanism by which integrated TCM alleviates sciatica has not yet been fully defined, and the effect of integrated TCM on gene expression in the peripheral blood of patients with sciatica is still unknown. We performed this study to investigate the effect of integrated TCM on peripheral blood gene expression in patients with sciatica and to explore new clues for studying the mechanism of integrated TCM in alleviating sciatica., Methods: We used a microarray to identify differentially expressed genes (DEGs) in the peripheral blood of patients with sciatica and healthy controls (DEGs-baseline), bioinformatic analysis to reveal the characteristics of DEGs-baseline, and the key genes that contribute to the gene dysregulation. A microarray was also used to identify DEGs in the peripheral blood of patients with sciatica after integrated TCM treatment compared with those at baseline, and the expression levels of DEGs were validated by qRT-PCR., Results: We identified 153 DEGs-baseline, which included 131 upregulated genes and 22 downregulated genes. Bioinformatic analysis revealed that most of the DEGs-baseline were related to immunity and the inflammatory response and that TLR4, MMP9, MPO, CAMP, RETN, TLR5, and IL1RN were key genes involved in the dysregulation of genes in the peripheral blood of patients with sciatica. The expression levels of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 were decreased in the peripheral blood of patients after integrated TCM treatment compared with that at baseline, which was accompanied by relief of pain., Conclusion: Integrated TCM treatment relieved pain while regulating the gene expression of TLR5, IL1RN, SLC8A1, RBM20, GPER1, IL27, SOCS1, and GRTP1-AS1 in the peripheral blood of patients with sciatica. Our study provides new clues for studying the mechanism of TCM in treating sciatica.

Background: Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. This study aimed to characterize the peripheral blood transcriptomic signature for sciatica., Methods: We used a microarray to identify differentially expressed genes in the peripheral blood of patients with sciatica compared with that of healthy controls, performed a functional analysis to reveal the peripheral blood transcriptomic signature for sciatica, and conducted a network analysis to identify key genes that contribute to the observed transcriptional changes. The expression levels of these key genes were assessed by qRT-PCR., Results: We found that 153 genes were differentially expressed in the peripheral blood of patients with sciatica compared with that of healthy controls, and 131 and 22 of these were upregulated and downregulated, respectively. A functional analysis revealed that these differentially expressed genes (DEGs) were strongly enriched for the inflammatory response or immunity. The network analysis revealed that a group of genes, most of which are related to the inflammatory response, played a key role in the dysregulation of these DEGs. These key genes are Toll-like receptor 4, matrix metallopeptidase 9, myeloperoxidase, cathelicidin antimicrobial peptide, resistin and Toll-like receptor 5, and a qRT-PCR analysis validated the higher transcript levels of these key genes in the peripheral blood of patients with sciatica than in that of healthy controls., Conclusion: We revealed inflammatory characteristics that serve as a peripheral blood transcriptomic signature for sciatica and identified genes that are essential for mRNA dysregulation in the peripheral blood of patients with sciatica.

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.

Background: There is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica., Methods: Primary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS). Participants underwent a standardised clinical assessment, lumbar spine MRI and a subsample (n = 119) had samples taken for biomarker analysis. Participants were classified having: a) clinically confirmed sciatica or referred leg pain, and then subdivided into those with (or without) MRI confirmed nerve root compression due to disc prolapse. Seventeen key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα and IL-6, were assayed in duplicate using commercial multiplex detection kits and measured using a Luminex suspension array system. Median biomarker levels were compared between the groups using a Mann Whitney U test. Multivariate logistic regression analysis was used to investigate the association between clinical measures and biomarker levels adjusted for possible confounders such as age, sex, and symptom duration., Results: No difference was found in the serum level of any of the 17 biomarkers tested in patients with (n = 93) or without (n = 26) clinically confirmed sciatica, nor between those with (n = 44) or without (n = 49) sciatica and MRI confirmed nerve root compression., Conclusion: In this cohort, no significant differences in serum levels of TNFα, IL-6 or any other biomarkers were seen between patients with sciatica and those with back pain with referred leg pain. These results suggest that in patients with low back-related leg pain, serum markers associated with inflammation do not discriminate between patients with or without clinically confirmed sciatica or between those with or without evidence of nerve root compression on MRI.

Background: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms?, Methods: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool., Results: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10)., Conclusion: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.

Objective: To study the clinical effects of electrical stimulation therapy on lumbar disc herniation-induced sciatica and its influence on peripheral reactive oxygen species (ROS) level., Methods: 100 patients with lumbar disc herniation-induced sciatica were selected, and were randomly divided into the control and research group. The control group was treated with traction and other basic therapies, while the research group was treated with electrical stimulation. The pain degrees, peripheral ROS levels and clinical effects prior to treatment and at 4 weeks after treatment were examined., Results: The total cure-remarkable-effectiveness rate of patients in research group was higher than that in control group (p<0.05). Before treatment, the pain rating index (PRI), present pain intensity (PPI) and visual analogue scale (VAS) score had no statistically significant differences between the two groups. After treatment, PRI, PPI and VAS scores in the two groups were lower than those prior to treatment; these indexes in research group were lower than those in control group, and the differences were statistically significant (p<0.05). After treatment, the peripheral ROS levels in the two groups were lower than those before treatment; it was lower in research group than that in control group (p<0.05)., Conclusion: Electrical stimulation has a significant effect in the treatment of lumbar disc herniation-induced sciatica, which can effectively reduce the pain, alleviate the clinical symptoms and signs of patients, regulate the peripheral ROS level, and prevent the oxidative damage of myocardial tissues.

Background: The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly diagnosed lumbar radicular pain (LRP) patients., Methods: The search was performed in Medline OVID, Embase, PsycInfo and Web of Science (2004 to 2015). Only prospective studies of patients with LRP addressing the role of genetic factors (genetic susceptibility) and pain biomarkers (proteins in serum) were included. Two independent reviewers extracted the data and assessed methodological quality., Results: The search identified 880 citations of which 15 fulfilled the inclusion criteria. Five genetic variants; i.e., OPRM1 rs1799971 G allele, COMT rs4680 G allele, MMP1 rs1799750 2G allele, IL1α rs1800587 T allele, IL1RN rs2234677 A allele, were associated with reduced recovery of LRP. Three biomarkers; i.e., TNFα, IL6 and IFNα, were associated with persistent LRP., Conclusion: The present results indicate that several genetic factors and biomarkers may predict slow recovery in LRP. Still, there is a need for replication of the findings. A stricter use of nomenclature is also highly necessary., Trial Registration: The review is registered PROSPERO 20 th of November 2015. Registration number is CRD42015029125 .

Purpose: The factors influencing the presence or absence of pain in sciatica secondary to disc herniation remain incompletely understood. We hypothesized that the imbalance in inflammatory cytokines is implicated in the generation of pain. In our study, serum levels of pro-inflammatory and anti-inflammatory cytokines were investigated among patients with severe sciatica; the serum levels were compared with those of patients with mild sciatica and healthy subjects., Methods: In this prospective study, blood protein levels of the pro-inflammatory cytokines, namely, interleukin-6 (IL-6), interleukin-8 (IL-8),and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines, namely, interleukin-4 (IL-4) and interleukin-10 (IL-10), of 58 patients with severe sciatica, 50 patients with mild sciatica, and 30 healthy control subjects were analyzed through ELISA. Physical and mental health symptoms were determined using the Oswestry Disability Index (ODI) and short form-36 (SF-36) questionnaire. Spearman rank correlation coefficient was also determined to calculate the correlation between the scores obtained from the questionnaires and the serum levels of cytokines., Results: IL-6 protein was detected in the three groups and median levels were about 1.5 times higher in patients with severe sciatica than the mild sciatica group (p = 0.02) and the controls (p = 0.03). Median levels of IL-8 in sciatica patients were higher than those of the healthy controls (p = 0.001 for severe sciatica, p = 0.02 for mild sciatica). The TNF-α protein values were approximately twofold higher in the severe sciatica group than in the mild sciatica group (p < 0.01) and in the healthy control group (p < 0.01). Median levels of IL-4 were about 2.5-fold higher in mild sciatica (p < 0.01) and about twofold higher in patients with severe sciatica (p = 0.012) when compared with controls. Median protein levels of IL-10 showed a trend to be higher in patients with mild sciatica compared with severe sciatica (p < 0.01) and with healthy controls (p < 0.01). ODI was significantly correlated with IL-6 (r = 0.394, p = 0.013), TNF-α (r = 0.629, p < 0.001), and IL-10 (r = -0.415, p = 0.009). ODI was not significantly correlated with IL-4 (r = -0.174, p = 0.29) and IL-8 (r = -0.133, p = 0.418)., Conclusions: These findings support our hypothesis that sciatica pain is accompanied by the imbalance in inflammatory cytokines.

Unlabelled: Epidemiological studies and meta-analyses report a strong relationship between chronic pain and abnormalities in glucose metabolism, but the exact relationship between chronic pain and insulin resistance in type 2 diabetes (T2D) remains unknown. Using a model of neuropathic thermal and tactile hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in Zucker Diabetic Fatty (ZDF) and Zucker Lean (ZL) littermates, we compared the recovery period of hypersensitivity and the progression of T2D and studied the possible involvement of insulin receptors (IRs) in the comorbidity of these 2 conditions. We found that the nociceptive thresholds to thermal and mechanical stimulation in naive ZDF rats were lower than in ZL littermates at 6 weeks of age. Although ZDF and ZL rats developed thermal and tactile hypersensitivity after CCI, it took a longer time nociceptive sensitivity to be restored in ZDF rats. Nerve injury accelerated the progression of T2D in ZDF rats, shown by an earlier onset of hyperglycemia, more severe hyperinsulinemia, and a higher concentration of glycosylated hemoglobin Alc 6 weeks after CCI, compared with those in naive ZDF and ZL rats. IR-immunoreactive cells were located across the central nervous system and skeletal muscles. In the central nervous system, IR coexpressed with a neuronal marker (neuronal nuclei) but not a glial marker (glial fibrillary acidic protein). There was a low level of IR expression in skeletal muscles of naive ZDF rats. In contrast, CCI reduced the IR expression in skeletal muscles as well as the ipsilateral spinal cord, primarily in the dorsal horn. In conclusion, our data suggest that the relationship between insulin resistance and chronic pain in ZDF rats is bidirectional and an impaired IR signaling system might be implicated in this reciprocal relationship., Perspective: Nerve injuries in genetically susceptible individuals might accelerate the development of insulin resistance as in T2D. A downregulated expression of IRs in the skeletal muscle innervated by the injured nerve is one of the underlying mechanisms., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The dynamics of possible markers of pain syndrome: pain pressure thresholds of intolerance (PTI) and natural antibodies to mediators of pain processing (nAbs) in blood serum at dorsalgia was studied. We have shown that most men and women had reduced PTIs. Night PTIs were lower than daytime PTIs regardless of the gender. The study of the content of nAbs to opioids and biogenic amines by ELISA have shown a prolonged maintenance of their elevated and high levels that could evoke long-term effect in pain chronization. Thus, the pressure algometry and ELISA of nAbs to pain processing mediators make it possible to assess the individual pain status objectively and, on this bases, to propose personal schemes of treatment.

It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The effects of pregabalin on neuropathic pain relief and the serum visfatin level were assessed using an experimental model of neuropathy in a study conducted on 40 male mice with sciatic nerve constriction. The mice were randomly assigned to 4 groups, each with 10 mice. The mice were subjected to experimental chronic partial constriction of the sciatic nerve and compared to sham-operated, saline-treated control mice (group I). The experimental groups (II-IV) were subjected to partial constriction of the left sciatic nerve. A series of behavioral tests, electrophysiological studies and biochemical measures were performed after 3 weeks of daily oral treatment with pregabalin (20 and 40 mg/kg in groups III and IV, respectively). The study revealed the actions of pregabalin against the nociceptive effects of chronic sciatic nerve constriction in mice (p < 0.01), including replenishment of the glutathione level (p < 0.05) and reduction of the serum visfatin level. No significant effect on the tissue malondialdehyde level was found for any of the pregabalin doses. The percentage differences in the maximum tetanic force between the ipsilateral and contra lateral legs were significant in both pregabalin-treated groups (p < 0.05). We concluded that pregabalin reduced the serum visfatin level and produced a dose-dependent antinociceptive antioxidant effect., (© 2015 S. Karger AG, Basel.)

There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

A quantitative, peripherally accessible biomarker for neuropathic pain has great potential to improve clinical outcomes. Based on the premise that peripheral and central immunity contribute to neuropathic pain mechanisms, we hypothesized that biomarkers could be identified from the whole blood of adult male rats, by integrating graded chronic constriction injury (CCI), ipsilateral lumbar dorsal quadrant (iLDQ) and whole blood transcriptomes, and pathway analysis with pain behavior. Correlational bioinformatics identified a range of putative biomarker genes for allodynia intensity, many encoding for proteins with a recognized role in immune/nociceptive mechanisms. A selection of these genes was validated in a separate replication study. Pathway analysis of the iLDQ transcriptome identified Fcγ and Fcε signaling pathways, among others. This study is the first to employ the whole blood transcriptome to identify pain biomarker panels. The novel correlational bioinformatics, developed here, selected such putative biomarkers based on a correlation with pain behavior and formation of signaling pathways with iLDQ genes. Future studies may demonstrate the predictive ability of these biomarker genes across other models and additional variables., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

Background: Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs., Aims/methods: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone., Results: Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice., Conclusion: Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data., (© 2011 European Federation of International Association for the Study of Pain Chapters.)

Recent studies have revealed that T lymphocytes play a role in neuropathic pain following nerve injury in rats through releasing several cytokines. Sirolimus is an immunosuppressive antibiotic inhibiting T cell activation. This study aimed to determine the effect of sirolimus on hyperalgesia and allodynia and on serum and spinal cord TNF-alpha, IL-1beta and IL-6 levels in rat neuropathic pain. Neuropathic pain was induced by loose ligation of the sciatic nerve and evaluated by tests measuring the mechanical hyperalgesia and allodynia. Sirolimus (0.75 and 1.5 mg/kg) was administered intraperitoneally once every 3 days for 2 weeks (7 doses totally). This dosing regimen revealed acceptable blood concentrations in neuropathic rats. Chronic constriction injury of the sciatic nerve resulted in hyperalgesia and allodynia. Serum levels of cytokines remained unchanged in neuropathic rats. However, TNF-alpha, but not IL-1beta or IL-6, protein level was increased in the spinal cord tissue as evaluated by Western blotting analysis. Treatment with sirolimus resulted in antihyperalgesic and antiallodynic effects and prevented the increased spinal cord TNF-alpha level. It seems that sirolimus could be a promising immunosuppressive agent in the treatment of neuropathic pain., (2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica., Methods: A nationally representative sample (n=8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample., Results: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% CI 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92; 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55)., Conclusions: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis.

In this prospective longitudinal study with a follow-up of 6 months, the course of serum concentration of C-reactive protein was measured by an ultrasensitive immunoassay in 31 patients with acute lumbosciatic pain and 41 patients with chronic low back pain. High-sensitive CRP (hsCRP), pain and clinical function were assessed at ten fixed time-points during follow-up. The course of hsCRP values was assessed in relation to the course of pain and clinical function adjusting for possible confounding factors. At the beginning of the study, there were no statistically significant differences in mean hsCRP levels in patients with acute lumbosciatic pain (1.49mg/l) compared to the levels obtained in patients with chronic low back pain (1.30mg/l) and those in a control group from the general population (1.26mg/l). In patients with acute lumbosciatic pain, hsCRP declined significantly in the initial period of 3 weeks with a corresponding decrease in pain and improvement in function and clinical evaluation as assessed with the straight leg raising test (SLR), whereas after this period, the course of the hsCRP did not correspond with the clinical parameters. In patients with chronic low back pain, hsCRP remained approximately constant throughout the whole period with no correlation with pain or function. As a conclusion, according to this study levels of hsCRP do not have a major clinical relevance when evaluating the long-term course of patients with acute lumbosciatic pain and chronic low back pain and therefore should not be taken into primary consideration when decisions on therapy are made.

Chronic pain can be considered a form of chronic stress, and chronic pain patients often have disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, including abnormal cortisol levels. In addition, chronic pain patients have an increased incidence of depression and anxiety, stress-related disorders that are frequently accompanied by disturbances in the limbic system (e.g. hippocampus and amygdala) and the HPA axis. Despite the fact that the literature supports a strong link between chronic pain, stress disorders, and limbic dysfunction, the mechanisms underlying the effects of chronic pain on the HPA axis and limbic system are not understood. The current study employs a rodent neuropathic pain model (chronic constriction injury (CCI) of the sciatic nerve) to assess the long-term impact of chronic pain on the HPA axis and limbic system. Adult male rats received CCI or sham surgery; nociceptive behavioral testing confirmed CCI-induced neuropathic pain. Tests of HPA axis function at 13-23 days postsurgery demonstrated that CCI did not affect indices of basal or restraint stress-induced HPA axis activity. CCI increased the expression of corticotrophin releasing hormone mRNA in the central amygdala, and not the paraventricular nucleus of the hypothalamus or the bed nucleus of the stria terminalis. Moreover, glucocorticoid receptor mRNA expression in CCI rats was increased in the medial and central amygdala, unaffected in the paraventricular nucleus, and decreased in the hippocampus. These results suggest that increased nociceptive sensitivity during chronic pain is associated with alterations in the limbic system, but is dissociated from HPA axis activation.

Background: The severity of pain from musculoskeletal disorders might be associated with high sensitivity C reactive protein (hsCRP), a sensitive marker of low grade systemic inflammation., Objective: To study the association between pain as assessed by a visual analogue scale (VAS) and hsCRP in patients with chronic low back pain and acute sciatic pain., Methods: Information on pain severity, determinants of hsCRP, and hsCRP values were obtained prospectively at up to 10 time points during six months in 72 consecutive patients (mean age 43.3 years; 59.7% female): 41 with chronic low back pain and 31 with acute sciatic pain. The association between severity of pain and raised (highest quartile) hsCRP values at any time point was estimated by multivariable logistic regression using generalised estimating equations to adjust odds ratios (OR) and their confidence intervals (CI) for intraindividual dependence of measurements., Results: Mean intensity of pain (VAS 0-10) at baseline was 4.9 and 5.5 in patients with chronic low back and acute sciatic pain, respectively. Highest v lowest tertile of average intensity of pain during the last 24 hours was associated with increased hsCRP levels among patients with acute sciatic pain (adjusted OR = 3.4 (95% CI, 1.1 to 10), but not in patients with chronic low back pain (adjusted OR = 0.87 (0.25 to 3.0))., Conclusions: Mean intensity of pain during the previous 24 hours as assessed by VAS was independently associated with high levels of hsCRP in patients with acute sciatic pain but not in those with chronic low back pain.

Study Design: Serum antibody titers against 10 different glycosphingolipids were investigated by enzyme-linked immunosorbent assay in three groups of patients: patients with acute sciatica (Group IA, radicular pain for 32 +/- 36 days, n = 68), a subgroup of these patients 4 years later (Group IB, n = 23), and patients undergoing lumbar discectomy because of disc herniation (Group II, n = 37)., Objectives: To investigate the immunologic response in sciatica patients by analyzing circulating autoantibodies against glycosphingolipids, molecules highly expressed in cells from the nervous system, and the possible correlation of such antibodies to clinical and imaging findings as well as to subjective symptoms., Summary of Background Data: The titers of glycosphingolipid antibodies are elevated in neurologic diseases with autoimmune stimulation such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy., Methods: Antiglycosphingolipid antibodies were assayed by a microtiter enzyme-linked immunosorbent assay method. Antibody titers were related to a healthy population by a method that judges all positive results (positive result = patient sera/pooled blood donor serum >2, at titer 1/400) as indicating a pathologic condition., Results: Increased levels of circulating antibodies against one or more glycosphingolipids were detected in 71% of patients with acute sciatica, in 61% of sciatica patients at a 4-year follow-up visit (eight antigens analyzed) and in 54% in patients undergoing discectomy. These frequencies were somewhat higher than, and in the last group similar to, those reported for generalized nervous system disorders with autoimmune involvement. In the acute sciatica patients, positive neurologic findings were associated with increased levels of two of the examined antibodies: 3'LM1 (immunoglobulin M and/or immunoglobulin G), P = 0.023, and GD1a (immunoglobulin M), P = 0.017., Conclusion: The presence of glycosphingolipid antibodies in patients with sciatica and disc herniation suggests an activation of the immune system and thus a process possibly involved in the pathophysiology of sciatica. The autoimmune response was not limited to antibodies against one specific glycosphingolipid target; rather, an overall increase in autoantibodies against nervous system-associated glycosphingolipids was observed. These results encourage further studies of the pathophysiologic and clinical relevance of autoimmune responses in patients with sciatica and disc herniation.

Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1beta IL-6, IL-8, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar disc herniation and sciatica. Pain duration and pain intensity (visual analogue scale, VAS) were recorded at inclusion, and a clinical examination was performed evaluating neurological findings. The extent of disc herniation (protrusion or extrusion/sequestration) was evaluated perioperatively. Normal concentrations of IL-1beta, IL-6, IFN-gamma and TNF-alpha were present in CSF and serum in almost all patients with lumbar disc herniation. The concentrations of IL-8 in CSF were increased in 12 out of 39 patients, and these increased levels of IL-8 correlated to a short duration of pain and to more pronounced herniation (extrusion or sequestration). No relationship between IL-8 concentrations in CSF and pain intensity, positive neurological findings or a positive straight leg-raising (SLR) test was found. The observation of increased concentrations of IL-8 in CSF in patients with a short duration of symptoms supports the concept of the initial involvement of inflammatory mechanisms after a disc herniation. The finding that most of the patients with increased concentrations of IL-8 in CSF had an extrusion or a sequestration may suggest that the increase in IL-8 is related to mechanical nerve root compression, but may also indicate a biochemical effect exerted by the herniated disc on the surrounding tissue. Further studies on the potential role of IL-8 as a biomarker for disc herniation are warranted.

Objective: To look for a systemic inflammatory response in patients with disk-related lumbosciatic syndrome by using an ultrasensitive (US) plasma C-reactive protein (CRP) assay, and to determine whether plasma CRP-US levels correlated with clinical and/or laboratory features., Patients and Methods: Plasma CRP was assayed using an enzyme-linked immunosorbent assay (ELISA) (detection limit, 5 microg/L) in patients with sciatica shown by computed tomography to be due to a disk herniation. Levels in 35 patients aged 23 to 64 years were compared to those in age- and sex-matched controls., Results: Mean CRP-US levels measured by ELISA were significantly higher in the patients than in the controls (1.68 vs 0.74 mg/L; P = 0.002). There was a trend toward higher CRP-US levels in the patients with more severe nerve root symptoms., Conclusion: The significantly higher plasma CRP-US levels by ELISA in our patients with disk-related lumbosciatic syndrome is consistent with a systemic inflammatory response to the local nerve root impingement.

We carried out a study of cerebrospinal fluid (CSF) proteins in 180 patients with sciatica caused by lumbar disc herniation to elucidate further the degree and mechanisms of protein elevations. The 63 controls were patients with tension headache or migraine without aura. The CSF/serum albumin ratios were higher in the patients (mean 8.84, SD 5.16) than in the controls (mean 5.60, SD 2.33). Similar differences were found for the CSF/serum IgG ratios and the CSF-total proteins. The CSF/serum albumin ratios, CSF/serum IgG ratios and the CSF-total protein concentrations were higher in men than in women among the patients. We suggest that the significant difference in ratio parameters between patients and controls indicates a leak of plasma albumin, most likely IgG, into the CSF in patients with sciatica. The leak was more pronounced in men. Also in the control group the CSF/serum albumin and CSF/serum IgG ratios were higher in men.

The search for diabetes in a patient with crural neuralgia is well established practice. The prevalence of diabetes in the general population is not known, and studies attempting to demonstrate a relationship between diabetes and radiculopathies have been inconclusive. In the present study, fasting and postprandial blood glucose determinations, as well as 14 other parameters, were analyzed in 88 patients with classical sciatica, 27 with crural neuralgia, and 42 with only back pain. Multidimensional statistical analysis revealed that patients with crural neuralgia were older than those with classical sciatica or only back pain, and that there were no differences in blood glucose regulation. The concept that diabetes is found more frequently in patients with crural neuralgia should be revised, since age appears to be the only factor responsible for changes in glucose regulation.

The authors present the results of determinations of beta-endorphin-like immunoreactivity in the plasma carried out before and after pinpoint receptor stimulation (prs) that is acupuncture in patients with long-standing pain. No significant differences were observed in this immunoreactivity after prs, and the clinical analgesic effect was independent of the level of this immunoreactivity and its changes during these procedures. On the other hand, a positive correlation was demonstrated between plasma beta-endorphin concentration and the neuroticism index as evaluated by Eysenck's personality inventory. The reliability of this observation requires, however, confirmation in a greater material.

The reported study was carried out in 26 patients hospitalized for protracted acute lumbosciatic pain syndrome lasting from 3 weeks to 3 months. In all patients the concentration of haemoglobin A1c was assessed in the erythrocytes by the colorimetric method of Thoma and Kutter. The control group comprised 14 healthy subjects in the same age group. The obtained results were subjected to statistical analysis which demonstrated an evident increase in the mean concentration of haemoglobin A1c in the erythrocytes in cases of lumbosciatic pain syndrome of protracted course.

A fibrinolytic defect is common in chronic back pain syndromes. Its role in the chronicity of these conditions is not fully understood. To elucidate the possible mechanisms, 11 patients with acute low back pain were studied over 12 months and compared with controls. The patients showed prolongation of the euglobulin lysis time throughout the study; the fibrin plate lysis area was initially normal but became abnormal within 2 weeks. In five patients, the symptoms resolved and the initial fibrinolytic defect improved. In contrast, the fibrinolytic defect remained in six patients with persistent pain. These results suggest that the fibrinolytic defect is secondary to mechanical damage but, if persistent, may become a secondary pathogenic factor associated with the chronicity of some back pain problems.

The blood serotonin level was determined by the fluorescent method of Ashcroft in 13 patients with sciatic pains during the pains and after the disappearance. The serotonin level was usually higher at the time of pains. In the discussion the author reminds that serotonin level falls during a migrainous attack and points out that the results of the present study confirm the specificity of sertonin level fall in migraine.

Study of the daily thythms of free 17-oxycorticosteroids in blood plasma of patients with tumors of the spinal cord and spine, discogenic pain syndrome, and of those who underwent plastic surgery for cranial defects revealed disturbances in the biorhythms of the adrenal cortex in patients with tumors of the spinal cord before operation. The postoperative period in all patients was characterized by the development of a stress reaction and paradoxical-type curves of the daily content of these hormones on the 3rd day with complete restoration of adrenal cortex biorhythms by the 15th day. The patients examined did not require special hormonotherapy.