Gut Microbiota Influences Neuropathic Pain Through Modulating Proinflammatory and Anti-inflammatory T Cells.

BACKGROUND: Gut microbiota, a consortium of diverse microorganisms residing in the gastrointestinal tract, has emerged as a key player in neuroinflammatory responses, supporting the functional relevance of the "gut-brain axis." Chronic-constriction injury of the sciatic nerve (CCI) is a commonly used animal model of neuropathic pain with a major input from T cell-mediated immune responses. In this article, we sought to examine whether gut microbiota influences CCI neuropathic pain, and, if so, whether T-cell immune responses are implicated. METHODS: We used a mixture of wide-spectrum oral antibiotics to perturbate gut microbiota in mice and then performed CCI in these animals. Nociceptive behaviors, including mechanical allodynia and thermal hyperalgesia, were examined before and after CCI. Additionally, we characterized the spinal cord infiltrating T cells by examining interferon (IFN)-γ, interleukin (IL)-17, and Foxp3. Using a Foxp3-GFP-DTR "knock-in" mouse model that allows punctual depletion of regulatory T cells, we interrogated the role of these cells in mediating the effects of gut microbiota in the context of CCI neuropathic pain. RESULTS: We found that oral antibiotics induced gut microbiota changes and attenuated the development of CCI neuropathic pain, as demonstrated by dampened mechanical allodynia and thermal hyperalgesia. Percentages of IFN-γ-producing Th1 cells and Foxp3+ regulatory T cells were significantly different between animals that received oral antibiotics (Th1 mean = 1.0, 95% confidence interval [CI], 0.9-1.2; Foxp3 mean = 8.1, 95% CI, 6.8-9.3) and those that received regular water (Th1 mean = 8.4, 95% CI, 7.8-9.0, P < .01 oral antibiotics versus water, Cohen's d = 18.8; Foxp 3 mean = 2.8, 95% CI, 2.2-3.3, P < .01 oral antibiotics versus water, Cohen's d = 6.2). These T cells characterized a skewing from a proinflammatory to an anti-inflammatory immune profile induced by gut microbiota changes. Moreover, we depleted Foxp3+ regulatory T cells and found that their depletion reversed the protection of neuropathic pain mediated by gut microbiota changes, along with a dramatic increase of IFN-γ-producing Th1 cell infiltration in the spinal cord (before depletion mean = 2.8%, 95% CI, 2.2-3.5; after depletion mean = 9.1%, 95% CI, 7.2-11.0, p < .01 before versus after, Cohen's d = 5.0). CONCLUSIONS: Gut microbiota plays a critical role in CCI neuropathic pain. This role is mediated, in part, through modulating proinflammatory and anti-inflammatory T cells.

Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs.

Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

Relationship between annular tear and presence of Propionibacterium acnes in lumbar intervertebral disc.

PURPOSE: Propionibacterium acnes (P. acnes) in the intervertebral disc may result in low back pain. The purpose of this study was to determine how P. acnes accesses the disc. METHODS: Patients with low back pain and/or sciatica were examined using X-ray and MRI before surgery. The intervertebral disc space height was measured on X-ray image. Disc and muscle samples were obtained from 46 patients undergoing discectomy at the lumbar spine. The tear of annulus was inspected before discectomy. In the disc and muscle tissue cultures, 16S rDNA gene specific for P. acnes was examined using PCR. RESULTS: The discs from 11 (23.9 %) patients were identified as 16S rDNA positive, in which two patients also had 16S rDNA in their muscles. 16S rDNA gene was significantly more likely to appear in the discs with annular tear than those without tear (P < 0.05). The disc space height was significantly decreased when the disc contained P. acnes. CONCLUSION: P. acnes is significantly more likely to be present in herniated discs with an annular tear than in herniated discs without such a tear. Since in the vast majority of these cases, no P. acnes was found in control muscle samples, a true infection with P. acnes is far more likely than a contamination.

Piomiositis del músculo piriforme / Pyomyositis of the piriformis muscle

Las infecciones profundas de músculos pélvicos son difíciles de diagnosticar por ocasionar signos físicos inespecíficos que sugieren otras patologías más comunes. Comunicamos el caso de un paciente de 12 años, sexo masculino, sano, con el antecedente de practicar danza. Consultó por dolor en región lumbar y glútea derecha, irradiado por cara posterior del muslo, de siete días de evolución. Recibió tratamiento sintomático sin respuesta. Presentó diarrea, fiebre y compromiso del estado general, evolucionando con shock séptico durante su estadía hospitalaria. La resonancia nuclear magnética pélvica fue compatible con piomiositis de músculo piriforme. Se aisló en sangre Staphylococcus aureus multisensible. Recibió apoyo multisistémico y tratamiento antibiótico, evolucionando satisfactoriamente. La piomiositis del músculo piriforme es una entidad poco frecuente, que requiere un elevado índice de sospecha, para un adecuado diagnóstico y tratamiento, siendo la terapia antibiótica y drenaje en caso de abscesos los pilares de éste último. Este tratamiento debe instaurarse en forma precoz, ya que su evolución puede ser potencialmente letal (AU)

Unfortunately, diagnosis of deep pelvic muscle infection is often delayed since they usually present with non-specific physical signs suggesting other more common diseases. The authors communicate a case of a previously healthy 12-year-old male whot practiced dancing regularly and suffered acute pain in the lumbar and right gluteal regions irradiated to the posterior side of the thigh for 1 week. He initially received symptomatic treatment with no success. He continued with diarrhea, fever and malaise. When he was admitted to hospital he suffered severe septic shock and multi-organ failure. Pelvis magnetic resonance imaging showed pyomyositis of the piriformis muscle. Multi-sensitive Staphylococcus aureus was isolated in blood cultures. Antibacterial treatment and multi systemic support were administered, resulting in a good outcome. Pyomyositis of the piriformis muscle is a rare condition that demands a high index of suspicion to make an adequate diagnosis and prompt treatment, including antibacterial treatment and drainage, particularly in case of abscess formation. This treatment should be established promptly since its outcome may be potentially lethal (AU)

Brucellar discitis as a cause of lumbar disc herniation: a case report.

Brucellosis is an infectious disease spread by consumption of non-pasteurized milk products or through contact with infected animals. Spinal involvement is one of the most important complications and the lumbar area is the most frequently affected site. Among the neurological consequences, nerve root compression can be a result of epidural abscess, granuloma or discitis secondary to vertebral body involvement. In this case report we present a 50-year-old male patient with brucellar discitis without spondylitis which caused lumbar disc herniation. We want to emphasize that discitis should also be considered in differential diagnosis of nerve root compression in suspected cases.

No evidence for presence of bacteria in modic type I changes.

BACKGROUND: Recent studies suggest an association between sciatica and Propionibacterium acnes. "Modic type I changes" in the vertebrae are closely associated with sciatica and lower back pain, and recent studies have questioned the ability of conventional magnetic resonance imaging (MRI) to differentiate between degenerative Modic type I changes and vertebral abnormalities caused by infection. PURPOSE: To test whether bacteria could be cultured from biopsies of Modic type I changes. MATERIAL AND METHODS: Twenty-four consecutive patients with Modic type I changes in lumbar vertebrae had a biopsy taken from the affected vertebra by a strict aseptic procedure. The biopsy was split into two specimens, which were inoculated into thioglycolate agar tubes in the surgical theatre and transported to the microbiology laboratory. In the laboratory, one specimen was streaked onto plates and analyzed for anaerobic and aerobic culture. The other tube was left unopened and incubated directly. Plates and tubes were incubated for 2 weeks and observed for visible growth. RESULTS: None of the biopsies yielded growth of anaerobic bacteria. In one patient, both biopsies yielded growth of Staphylococcus epidermidis, and in another patient coagulase-negative staphylococci were isolated from one biopsy. Both patients received oral antibiotics without convincing effect on symptoms. CONCLUSION: Our results showed no evidence of bacteria in vertebrae with Modic type I changes. The isolation of staphylococci from two patients probably represented contamination.

Propionibacterium acnes contamination in lumbar disc surgery.

Previous studies have shown that Propionibacterium acnes may be responsible for low-grade infection of the intervertebral discs of patients with severe sciatica. The aim of this study was to prospectively investigate the presence of bacteria in disc fragment samples obtained during surgery for lumbar disc herniation. P. acnes was cultured from disc fragments in two (3.7%) of 54 patients studied. In addition, control cultures taken from ligamentum flavum and muscle from these two patients were also positive for P. acnes. Similar control cultures were positive for P. acnes from a further ten (18.5%) patients. Four air samples taken during surgery all contained P. acnes; the organism was also found from three of 54 laminar flow control cultures. Sample contamination appears the most likely cause for the presence of P. acnes in the lumbar disc fragment cultures.

Association between sciatica and microbial infection: true infection or culture contamination?

STUDY DESIGN: Discs were cultured during discectomy from patients with back pain, sciatica, and radiologic evidence of disc herniation causing nerve root compression. OBJECTIVE: To investigate the claim of culpability of bacteria in causing the local inflammatory process seen in patients with disc herniation and radiculopathy. SUMMARY OF BACKGROUND DATA: Bacteria have been cultured from intervertebral discs of patients with sciatica. An infectious etiology for sciatica could have a dramatic effect on treatment options for this common problem. METHODS: To minimize the risk of contamination, the surgeon performed processing and culturing procedures intraoperatively under stringent sterile conditions. Immediately following disc excision, the specimens were divided into 4 pieces, and cultured in various aerobic and anaerobic culture mediums that were incubated for 2 weeks. RESULTS: The 120 specimens from 30 patients underwent bacterial culture growth: 116 were sterile, an 4 aerobic cultures (2 patients) grew coagulase-negative staphylococci, suggestive of contamination. CONCLUSIONS: These results refute the hypothesis that microbial infection plays a role in the pathogenesis of sciatica. It is possible that bacterial growth from discs reported in previous studies was at least partly related to contamination, which we painstakingly avoided by application of rigorous aseptic techniques.

Brucellar spondylo-discitis with rapidly progressive spinal epidural abscess presenting with sciatica.

STUDY DESIGN: Case report. OBJECTIVE: To present a patient with spinal brucellosis, which was initially presented with sciatica and misdiagnosed as a lumbar disc herniation owing to nonspecific neurological and radiological findings. The delay in diagnosis led to rapid progression of the disease and complications. SETTING: Department of Neurosurgery at a tertiary university teaching hospital (Sutcu Imam University Medical Center in Turkey). CASE REPORT: A 57-year-old woman with a history of low-back pain for 6 months, fatigue, and severe left-sided sciatica for the last 3 months presented to our hospital. Three months earlier, at another hospital, she had had a negative Rose-Bengal test for brucellosis and a lumbar computed tomography performed at that time showed only minimal L4-5 annular bulging. For 2 months, she was treated with analgesics for 'lumbar disc herniation' without relief of pain. On presentation to our department, her magnetic resonance imaging (MRI) examination showed edema and minimal annular bulging at L3-4 and L4-5. When her Rose-Bengal test returned positive, she was started on triple antibiotics for presumed Brucella infection. When symptoms and neurologic signs worsened while taking antibiotics, repeat MRI scan showed a spinal epidural abscess at the L4-5 level. Emergent surgery and 8 weeks of antibiotics resulted in cure. CONCLUSION: In areas endemic for brucellosis, subtle historical and exam features should be sought to exclude an infection such as brucellar sponylo-discitis. Appropriate serological tests should be readily available to confirm or exclude this diagnosis in selected patients, to avoid delays in antibiotic treatment.

[An abscess of the piriforme muscle as a rare cause of sciatic neuralgia. A case report]. / Ropien miesnia gruszkowatego jako rzadka przyczyna rwy kulszowej -- opis przypadku.

The rare cause of sciatic neuralgia, an abscess in the sciatic foramen, is presented. The most common causes of sciatic neuralgia are discussed. We analyse correlations between symptoms found in a young woman and anatomical structures of the supra- and infrapiriforme foramen and their neighborhood.

Determinants of lumbar artery occlusion among patients with sciatica: a three-year follow-up with magnetic resonance angiography.

We showed previously that chronic Chlamydia pneumoniae infection increases the risk of lumbar artery occlusion. We did not evaluate, however, the effect of other risk factors for cardiovascular diseases in combination with this chronic infection. The purpose of this study was to investigate the combined effect of chronic C. pneumoniae infection and other known determinants of artery occlusion in a population of sciatica patients. Two-dimensional time-of-flight magnetic resonance angiography (MRA) was used to evaluate lumbar arteries at baseline and three years. The arteries on both sides (L1-L4) were evaluated visually and scored as normal, narrowed or occluded. Logistic regression analysis was performed separately for baseline total arterial stenosis and each L1-L4 segmental artery pair, and for incident new stenosis during the follow-up period. The determinants analyzed included age, body mass index (BMI, kg/m(2)), education, gender, and smoking, in addition to presence of chronic C. pneumoniae infection. MRA was obtained at baseline for 147 patients and at 3 years for 134 patients. Sixty-four (47.8%) of 134 patients had new arterial stenosis. Total incidence of new arterial stenosis was distributed quite evenly between the individual segmental levels, varying from 12.7 to 18.6%. BMI was the only predictor of new arterial stenosis (odds ratio (OR) 1.13). A reasonable logistic model could be established only for baseline L4 and total arterial scores. At L4, education was a protective factor (OR 0.07), whereas age (OR for the oldest age group 6.7) and BMI (OR 1.17) were associated with increased risk of occlusion. For total arterial score, chronic C. pneumoniae infection was an independent determinant of arterial occlusion, increasing the risk to almost eightfold. Additionally, BMI (OR 1.16), and age (for the oldest age group OR 11.4) were significant determinants for stenosis. Smoking was not statistically significant. As chronic C. pneumoniae infection was an independent determinant of lumbar artery occlusion, treatments of this chronic infection may have an impact on lumbar diseases. The importance of BMI for new arterial stenosis suggests that weight reduction may also have a beneficial effect in lumbar artery disease.

[Clinical course of Lyme borreliosis with respect to the initial disease manifestation in Bialowieza residents]. / Analiza przebiegu boreliozy z Lyme w zaleznosci od pierwotnej postaci klinicznej choroby u mieszkanców Bialowiezy.

The aim of the study was to evaluate relationship between initial manifestation of Lyme borreliosis and further course of the disease. Files and questionnaires regarding present and past course of the disease were evaluated in 138 residents of Bialowieza village, suffering previously from Lyme borreliosis. Present arthralgia was the most frequently reported by persons who initially were diagnosed as suffering from Lyme arthritis. Ischialgia and brachialgia were the most prevalent in patients with previous neuroboreliosis. Psychiatric evaluation demonstrated significantly more frequent prevalence of sleep and cognitive disturbances in persons with previously diagnosed neuroboreliosis. Persons with initial joint manifestations of Lyme borreliosis more frequently report arthralgia in further follow-up. Primary manifestation of the disease as neuroboreliosis increase risk of subsequent disturbances of sleep and cognition.

Chronic Chlamydia pneumoniae infection increases the risk of occlusion of lumbar segmental arteries of patients with sciatica: a 3-year follow-up study.

STUDY DESIGN: A magnetic resonance imaging follow-up study of lumbar arteries among patients with sciatica with chronic Chlamydia pneumoniae infection. OBJECTIVE: To determine whether chronic infection causes occlusion of lumbar arteries. SUMMARY OF BACKGROUND DATA: C. pneumoniae infection is associated with coronary heart disease, and the infectious pathogen has also been detected in abdominal aortic aneurysms and in atherosclerotic plaques. No studies are available on the effect of this infectious agent on lumbar arteries. METHODS: Chronic infection was defined as persistent high positive immunoglobulin G and/or immunoglobulin A antibodies and/or the presence of immune complexes. The lumbar arteries, evaluated with two-dimensional time-of-flight magnetic resonance angiography, were scored as normal, narrowed, or occluded. The differences in the segmental and whole lumbar spine (segments L1-L4) sum of arterial occlusion at baseline and at 3 years, and the incidence of new arterial stenosis were compared in patients with and without chronic infection using the Kolmogorov-Smirnov test. RESULTS: Patients with chronic infection were more likely to be persistent smokers (P = 0.006), male (P = 0.04), and more obese (P = 0.02) compared to patients with normal antibody levels. They had significantly higher degree of arterial stenosis at L4 segment at baseline and at 3 years (P = 0.001 and 0.002, respectively), in the whole lumbar spine at baseline and at 3 years (P < 0.001 for both), and at L1 and L3 segments at 3 years (P = 0.013 for both). The incidence of new arterial stenosis was similar in both patient groups. Patients with chronic infection also had significantly higher grade of endplate degeneration at L4-L5 (P = 0.008). CONCLUSIONS: The results of this study suggest that chronic C. pneumoniae infection may induce stenosis of lumbar arteries.

Spinal epidural abscess: an unusual cause of sciatica.

A previously healthy patient was admitted to our hospital because of low back pain and sciatica. For 4 weeks preceding the admission, he had been treated with nonsteroidal antiinflammatory analgetics and bed rest with a clinical diagnosis of lumbar disc herniation. On admission, the patient was subfebrile but developed general symptoms of septic infection by the next day. Computed tomography and magnetic resonance imaging of the lumbar spine revealed a spinal epidural abscess and spondylodiscitis at the L5-S1 level. During an emergency laminotomy, gross pus in abundance was evacuated from the epidural space; microbiological cultures from the pus and blood yielded Staphylococcus aureus. The unique clinical presentation of our patient combined with merely indolent symptoms of infection delayed the correct diagnosis. We are not aware of any similar reports of patients with lower spinal epidural abscess whose primary presentation was sciatic pain.

Herpes simplex virus type I from a patient with radiculoneuropathy.

Herpes simplex virus type I was isolated from the CSF of a patient with atypical lumbosacral pain. The features of this case are unusual and important in light of the current understanding of herpes-simplex-virus-associated neurologic disease.