Sex, pain, and the microbiome: The relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals.

BACKGROUND AND AIM: Relative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can modulate nervous system functioning, including pain signaling pathways. We hypothesized that the gut microbiota and critical components of the gut-brain axis might influence electrical pain thresholds. Further, we hypothesized that sex, menstrual cycle, and hormonal contraceptive use might account for inter-sex differences in pain perception. METHODS: Healthy, non-obese males (N = 15) and females (N = 16), (nine of whom were using hormonal contraceptives), were recruited. Male subjects were invited to undergo testing once, whereas females were invited three times across the menstrual cycle, based on self-reported early follicular (EF), late follicular (LF), or mid-luteal (ML) phase. On test days, electrical stimulation on the right ankle was performed; salivary cortisol levels were measured in the morning; levels of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), pro-inflammatory cytokines were assessed in plasma, and microbiota composition and short-chain fatty acids (SCFAs) levels were determined in fecal samples. RESULTS: We observed that the pain tolerance threshold/pain sensation threshold (PTT/PST) ratio was significantly lesser in women than men, but not PST or PTT alone. Further, hormonal contraceptive use was associated with increased LBP levels (LF & ML phase), whilst sCD14 levels or inflammatory cytokines were not affected. Interestingly, in women, hormonal contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium, and the relative abundances of certain bacterial genera correlated positively with pain sensation thresholds (Prevotella and Megasphera) during the LF phase and cortisol awakening response (Anaerofustis) during the ML phase. In comparison with men, women displayed overall stronger associations between i) SCFAs data, ii) cortisol data, iii) inflammatory cytokines and PTT and PST. DISCUSSION AND CONCLUSION: Our findings support the hypothesis that the gut microbiota may be one of the factors determining the physiological inter-sex differences in pain perception. Further research is needed to investigate the molecular mechanisms by which specific sex hormones and gut microbes modulate pain signaling pathways, but this study highlights the possibilities for innovative individual targeted therapies for pain management.

Intra-operative imaging for spinal level localisation in lumbar surgery.

Study Design: Retrospective review of the practice of 3 surgeons in a single centre during a 1-year period. Objective: We aimed to investigate our adherence to the Society of British Neurological Surgeons (SBNS) guidelines regarding intra-operative imaging during lumbar surgery and to determine if this has any impact on length of surgery or complications rates, in particular rates of wrong-level surgery. Background: The SBNS recommends three x-rays for intra-operative spinal localisation - one prior to incision, the second after exposure of the laminae and before the commencement of decompression, and the third at the end of the operation to confirm the adequacy of decompression. At our centre, surgeon A performs x-rays 1 and 3 routinely, and x-ray 2 in cases where the anatomy is uncertain, surgeon B performs x-ray 2 only, and the practice of surgeon C varies depending on the complexity of cases. Method: We reviewed the surgical logbooks of 3 consultant neurosurgeons in our centre for the 1-year period between October 2015 and October 2016. Our study included 301 patients who had undergone lumbar decompression or lumbar discectomy during this period. Results: There were no cases of wrong-level surgery. The incorrect spinal level was initially exposed in 13 cases (4.3%). 10 of these had x-ray 2 only, 1 had x-ray 1, 1 had x-rays 1 and 2, and 1 had all 3 x-rays. Surgeon B performed 8 of these cases, four were performed by surgeon C, and 1 by surgeon A. The median duration of surgery was 80 minutes for lumbar decompression and 67.5 minutes for lumbar discectomy. The median duration of surgery in patients in whom the wrong level was initially exposed was 85 minutes for lumbar decompression and 80 minutes for lumbar discectomy. Conclusion: Performance of the 3 recommended x-rays may increase the identification of wrong-level exposures before the commencement of decompression and may reduce the length of surgery.

Case Report: Recurrent pediatric cavernous malformation of the trigeminal nerve.

Background: Most cavernous malformations (CM) usually involve the parenchyma and rarely occur in cranial nerves. Recurrence of CM associated with cranial nerves after surgical resection has not been previously reported. Case description: This paper describes the case of an 11-year-old girl who presented with left otalgia and headache because of a left trigeminal cavernous malformation. She underwent radical resection via a left retrosigmoid approach while sparing the trigeminal nerve. Surveillance imaging at 18 months demonstrated recurrence along the length of the trigeminal nerve into Meckel's cave with significant extension into the middle cerebellar peduncle. Subsequent re-operation via an extended middle fossa approach with anterior petrosectomy enabled complete resection with division of the trigeminal nerve. Postoperatively, she had a transient left facial paresis, and right hemiparesis that resolved within 48 h. Conclusion: This case highlights the importance of close postoperative surveillance in CM associated with cranial nerves as recurrence after nerve-sparing resection is possible. Surgical treatment due to the morphology of significant recurrence required the use of a complex skull base approach through a new corridor to achieve optimal clinical outcome.

A Prospective Analysis of Complications of Intracranial Tumor Surgery.

Aims There is a recent trend toward delivering neurosurgical care in large supraregional centers with intradepartmental subspecialization. We report a 14-year prospective audit of a single surgeon's experience of intracranial tumor surgery with an emphasis on complications. Methods A total of 616 procedures were performed on 596 patients of which 321 were male and 275 were female (age range: 1-84 years). Tumors were categorized as glioma, meningioma, metastasis, and other. Complications were recorded as infection, intracranial hematoma, neurologic deterioration, and death. Results Of the 305 patients who underwent glioma surgery, 4 (1.3%) developed a hematoma, 4 (1.3%) had neurologic deterioration, 5 (1.6%) died within 30 days of surgery, and 1 (0.33%) had an infection. Of the 120 patients who underwent surgery for meningioma, 8 (6.6%) developed an infection, 1 (0.83%) developed a hematoma, and 7 (5.8%) had neurologic deterioration. Of the 59 patients who underwent surgery for brain metastasis, 1 (1.7%) had neurologic deterioration. Of the remaining patients, 4 (3.0%) developed infection and 6 (4.5%) had neurologic deterioration. Conclusions The overall complication rate was infection, 2.1%; hematoma, 0.8%; neurologic deterioration, 2.9%; and death, 0.8%. These results compare favorably with published series.

Interdural Spinal Cyst: A Rare Clinical Entity.

BACKGROUND: For more than 2 decades, dural spinal cysts have been broadly classified as extradural and intradural. CASE DESCRIPTION: A 40-year-old woman presented with radicular thoracic pain. Intraoperative findings showed the cyst to be present within the dura itself. CONCLUSIONS: We suggest a revised classification of spinal dural cysts. This case highlights that, during surgery for spinal meningeal cysts, surgeons should bear in mind the possibility of an interdural cyst. This may help avoid inadvertent tears in the deep layers of such cysts, thus maintaining dural patency.

Sex-dependent activity of the spinal excitatory amino acid transporter: Role of estrous cycle.

Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. Thus, we aimed to investigate sex differences in the spinal cord glutamate uptake and how it varies across the estrous cycle. The activity of the glutamate transporters, excitatory amino acid transporters (EAATs) was assessed using an ex vivo aspartate radioactive uptake assay in the lumbosacral spinal cord in Sprague-Dawley male and female rats. The gene expression of EAATs, glutamate receptor subunits NR1 and NR2B and the estrogen receptors ERα & ERß in the spinal cord were also analyzed. EAAT activity was lower in females, particularly during the estrus phase, and this was the only cycle stage that was responsive to the pharmacological effects of the EAATs activator riluzole. Interestingly, EAAT1 mRNA expression was lower in high-estrogen and high-ERα states compared to diestrus in females. We conclude that the Spinal EAAT activity in females is different to that in males, and varies across the estrous cycle. Furthermore, the expression levels of estrogen receptors also showed a cycle-dependent pattern that may affect EAATs function and expression.

Estrous cycle influences excitatory amino acid transport and visceral pain sensitivity in the rat: effects of early-life stress.

BACKGROUND: Early-life stress (ELS) is a recognized risk factor for chronic pain disorders, and females appear to be more sensitive to the negative effects of stress. Moreover, estrous cycle-related fluctuations in estrogen levels have been linked with alternating pain sensitivity. Aberrant central circuitry involving both the anterior cingulate cortex (ACC) and the lumbosacral spinal cord has also been implicated in the modulation of visceral pain in clinical and preclinical studies. Here we further investigate changes in visceral pain sensitivity and central glutamatergic systems in rats with respect to estrous cycle and ELS. METHODS: We investigated visceral sensitivity in adult female Sprague-Dawley rats, which had undergone maternal separation (MS) in early life or remained non-separated (NS), by performing colorectal distension (CRD). We also assessed excitatory amino acid uptake through excitatory amino acid transporters (EAATs) in the lumbosacral spinal cord and ACC. RESULTS: NS animals in proestrus and estrus exhibited reduced EAAT uptake and decreased threshold to CRD. Moreover, total pain behaviors were increased in these stages. MS rats exhibited lower pain thresholds and higher total pain behaviors to CRD across all stages of the estrous cycle. Interestingly, cortical EAAT function in MS rats was inhibited in the low estrogen state-an effect completely opposite to that seen in NS rats. CONCLUSIONS: This data confirms that estrous cycle and ELS are significant factors in visceral sensitivity and fluctuations in EAAT function may be a perpetuating factor mediating central sensitization.

A large un-ruptured abdominal aortic aneurysm causing pulmonary embolism.

A 79 years old woman presented in a peripheral hospital with dyspnea, right-sided pleuritic chest pain and cough for 3 days. On examination, she was tachycardiac and tachypneic. She had reduced air entry bilaterally on auscultation. Computed tomography-pulmonary angiogram, performed in peripheral Hospital, confirmed the diagnosis of pulmonary embolism, and she was commenced on warfarin. Ultrasonography showed no evidence of deep venous thrombosis in legs; however, ultrasound of the abdomen revealed an aortic aneurysm. She was hemodynamically stable on transfer to vascular surgery department, and her complete clinical examination revealed a pulsatile mass in the central abdomen. Computed tomography angiogram of aorta showed 8.7-cm abdominal aortic aneurysm. Venogram performed during inferior vena cava (IVC) filter insertion showed that IVC was displaced and compressed due to this large aortic aneurysm, causing thromboembolism. An open repair of the aneurysm was performed with uneventful recovery.

Headache during haemodialysis in a patient with shunt: a cause for concern?

A 20-year-old woman with a functioning ventriculoperitoneal (VP) shunt consistently reported unbearable vertex headaches and nausea during the last hour of her haemodialysis (HD) sessions. After one particularly severe episode, which was associated with vomiting, restlessness and blurred vision, her team suspected that she was developing dialysis disequilibrium syndrome. She improved fully on cessation of HD, requiring simple analgaesia only, and continued dialysis three times per week. Several more distressing episodes of nausea and headaches compelled us to give intravenous mannitol during HD, resulting in temporary improvement. Subsequently, shorter and more frequent dialysis sessions along with intravenous mannitol resulted in satisfactory clinical response.

"Unusual brain stone": heavily calcified primary neoplasm with some features suggestive of angiocentric glioma.

This 40-year-old man presented with a 5-month history of progressive right-sided headache associated with visual blurring. He also had a history of epilepsy but had been seizure free with medication for the past 10 years. An initial CT scan of his brain performed 16 years previously had revealed a small area of calcification in the right parietal region. In the current presentation, he had a left-sided homonymous hemianopia but no other neurological deficits. A CT scan of his brain showed a much larger calcified, partly cystic lesion in the right parietal region. Because he was symptomatic, the lesion was excised and the cyst was drained. Histological examination of the excised tissue showed an unusual primary tumor that was difficult to classify but had some features of angiocentric glioma. The heavy calcification, mixed-density cell population, and regions with features of angiocentric glioma were most unusual. The patient remained asymptomatic 5 years after surgery, and follow-up scans did not show recurrence.

An iatrogenic popliteal pseudoaneurysm masked under compartment syndrome of leg.

This case describes a 60-year-old gentleman who presented with a pulsating mass behind his knee. Before this, he had a fasciotomy for suspected compartment syndrome of leg following knee arthroscopy, but this failed to resolve his leg symptoms. He was hemodynamically stable on presentation. His left calf was swollen with a circumference of 3 cm greater than right. There was a large pulsating mass palpable in his left popliteal fossa. Distal neurovascular status of the leg was intact. He had a normal cardiovascular, respiratory, abdominal and neurological examination. Ultrasound showed a cystic mass in the popliteal fossa suggestive of aneurysm. CT angiogram demonstrated a 6 × 5 × 4 cm pseudoaneurysm compressing and displacing the left popliteal artery with satisfactory three-vessel run-off. An emergency repair was performed. An arteriotomy was identified at the proximal end of pseudoaneurysm and it was closed with a patch of small saphenous vein. It led to a good clinical outcome.

Abscess or tumour? Lumbar spinal abscess mimicking a filum terminale tumour.

A 62-year-old woman presented with a 4-month history of central lower backache and a 2-week history of progressive bilateral leg weakness. She also complained of numbness on her left thigh and gluteal region, associated with urinary hesitancy and constipation. On examination, she had bilateral partial foot drop, absent knee and ankle reflexes and a negative Babinski's reflex and associated hyperaesthesia in L3 distribution bilaterally with decreased anal tone. Laboratory results revealed normal inflammatory markers. MRI scan demonstrated a large uniformly enhancing lesion in the filum terminale suggestive of a lumbar spinal tumour. An emergency spinal laminectomy from L3 to S2 was performed. Per operatively, the duramater was thickened and hyperaemic. The histopathology report suggested inflammation with no evidence of malignancy. Tissue specimen of cultured Staphylococcus aureus was sensitive to flucloxacillin. A final diagnosis of lumbar spinal abscess was made and subsequent antibiotic treatment led to good clinical recovery.