GPR55 contributes to neutrophil recruitment and mechanical pain induction after spinal cord compression in mice.

Pain transmission and processing in the nervous system are modulated by various biologically active substances, including lysophospholipids, through direct and indirect actions on the somatosensory pathway. Lysophosphatidylglucoside (LysoPtdGlc) was recently identified as a structurally unique lysophospholipid that exerts biological actions via the G protein-coupled receptor GPR55. Here, we demonstrated that GPR55-knockout (KO) mice show impaired induction of mechanical pain hypersensitivity in a model of spinal cord compression (SCC) without the same change in the models of peripheral tissue inflammation and peripheral nerve injury. Among these models, only SCC recruited peripheral inflammatory cells (neutrophils, monocytes/macrophages, and CD3+ T-cells) in the spinal dorsal horn (SDH), and GPR55-KO blunted these recruitments. Neutrophils were the first cells recruited to the SDH, and their depletion suppressed the induction of SCC-induced mechanical hypersensitivity and inflammatory responses in compressed SDH. Furthermore, we found that PtdGlc was present in the SDH and that intrathecal administration of an inhibitor of secretory phospholipase A2 (an enzyme required for producing LysoPtdGlc from PtdGlc) reduced neutrophil recruitment to compressed SDH and suppressed pain induction. Finally, by screening compounds from a chemical library, we identified auranofin as a clinically used drug with an inhibitory effect on mouse and human GPR55. Systemically administered auranofin to mice with SCC effectively suppressed spinal neutrophil infiltration and pain hypersensitivity. These results suggest that GPR55 signaling contributes to the induction of inflammatory responses and chronic pain after SCC via the recruitment of neutrophils and may provide a new target for reducing pain induction after spinal cord compression, such as spinal canal stenosis.

Mechanical pain of the lower extremity after compression of the upper spinal cord involves signal transducer and activator of transcription 3-dependent reactive astrocytes and interleukin-6.

Chronic pain is one of the main symptoms of spinal disorders such as spinal canal stenosis. A major cause of this pain is related to compression of the spinal cord, and chronic pain can develop at the level of the compressed spinal segment. However, in many patients chronic pain arises in an area that does not correspond to the compressed segment, and the underlying mechanism involved remains unknown. This was investigated in the present study using a mouse model of spinal cord compression in which mechanical pain of the hindpaws develops after compression of the first lumbar segment (L1) of the spinal cord. Compression induced the activation of astrocytes in the L1 spinal dorsal horn (SDH)-but not the L4 SDH that corresponds to the hindpaws-and activated signal transducer and activator of transcription 3 (STAT3). Suppressing reactive astrocytes by expressing a dominant negative form of STAT3 (dnSTAT3) in the compressed SDH prevented mechanical pain. Expression of interleukin (IL)-6 was also upregulated in the compressed SDH, and it was inhibited by astrocytic expression of dnSTAT3. Intrathecal administration of a neutralizing anti-IL-6 antibody reversed the compression-induced mechanical pain. These results suggest that astrocytic STAT3 and IL-6 in the compressed SDH are involved in remote mechanical pain observed in the lower extremity, and may provide a target for treating chronic pain associated with spinal cord compression such as spinal canal stenosis.

Safety and Clinical Results of Continuous Low-Dose Aspirin in Microendoscopic Laminectomy.

Introduction: It remains controversial whether it is better to continue oral low-dose aspirin (LDA) during the perioperative period in spinal surgery. This study aims to evaluate the safety of continued LDA administration in the perioperative periods of microendoscopic laminectomy (MEL) by assessing perioperative complications and clinical outcomes. Methods: We ultimately included 88 patients (35 males, 53 females) who underwent one level of MEL for lumbar spinal canal stenosis from April 2016 to March 2022. Patients who did not undergo anticoagulation therapy were classified into Group A (65 patients), those who stopped anticoagulation therapy at the perioperative periods were classified into Group B (9 patients), and those who continued oral administration of LDA throughout the perioperative periods were classified into Group C (14 patients). Surgery time, intraoperative estimate blood loss (EBL), differences between hemoglobin (Hb) and platelet (Plt) before and after surgery, perioperative complications, and cross-sectional area of hematoma and dural sac on MRI taken within 1 week and at 6 months or more after surgery were assessed between three groups. The EuroQol-5 dimensions (EQ-5D), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were also evaluated as the clinical outcomes. Results: There was no statistically significant difference between the three groups in operation time, intraoperative EBL, differences between Hb and Plt before and after surgery, and cross-sectional area of hematoma and dural sac on MRI. A case of hematoma removal was confirmed in Group A. There was also no statistically significant difference between the three groups in EQ-5D, ODI, and each domain of JOABPEQ. Conclusions: The continuation of LDA throughout the perioperative periods did not affect perioperative complications and clinical outcomes of one-level MEL. In MEL, it might be possible to continue oral administration of LDA throughout the perioperative periods.

A Presenile Patient with Filar Lipoma Who Developed Tethered Spinal Cord Syndrome Triggered by Lumbar Canal Stenosis.

Lumbar canal stenosis (LCS) has been reported as a precipitating factor by which a tethered spinal cord, which is asymptomatic during childhood, develops into tethered cord syndrome (TCS) in adulthood. However, only a few reports on surgical strategies for such cases are available. A 64-year-old woman presented with unbearable pain in the left buttock and dorsal aspect of the thigh approximately 1 year ago. Magnetic resonance imaging showed cord tethering with a filar-type spinal lipoma and LCS due to the thickening of the ligamentum flavum at the L4-5 vertebral level. Five months after the decompressive laminectomy for the treatment of LCS, an untethering surgery was performed at the dural cul-de-sac at the S4 level. The severed end of the filum was elevated rostrally by 7 mm, and the pain subsided postoperatively. This case study shows that surgeries for both lesions should be indicated for adult-onset TCS triggered by LCS.

Osteoid Osteoma Can Occur at the Pars Interarticularis of the Lumbar Spine, Leading to Misdiagnosis of Lumbar Spondylolysis.

BACKGROUND Osteoid osteomas are benign bone-forming tumors characterized by local inflammation and pain. They are also characterized by a small osteolytic lesion (nidus). Spondylolysis is a defect of the pars interarticularis, which may lead to stress fractures, and is a common cause of low back pain in adolescence. Osteoid osteoma occurs predominantly in the posterior elements of the spine. Magnetic resonance imaging (MRI) signal abnormality suggesting bone marrow edema is a common finding in osteoid osteoma and early-stage spondylolysis without prominent defect. CASE REPORT An 18-year-old male was suffering from low back pain. He was diagnosed with lumbar spondylolysis on initial MRI and computed tomography (CT). Subsequent thin-slice CT demonstrated a nidus at the pars interarticularis, and variously-sliced MRI could detect widespread bone marrow edema. On the diagnosis of an osteoid osteoma, the nidus and surrounding osteosclerosis were resected. The patient's pain disappeared after surgery. CONCLUSIONS Osteoid osteoma in the pars interarticularis can be difficult to diagnosis, because MRI and CT findings for osteoid osteoma at the pars interarticularis are similar to those of the lumbar spondylolysis. The possibility of osteoid osteoma should be kept in mind when examining adolescents with low back pain.

The morphological relationship between lumbosacral transitional vertebrae and lumbosacral pedicle asymmetry.

INTRODUCTION: The clinical significance of lumbosacral transitional vertebrae (LSTV) has been reported. However, the association between LSTV and lumbosacral pedicle anatomical anomaly has not been investigated. We hypothesized that LSTV might be associated with lumbosacral anatomical anomaly. The purpose of this study was to examine the morphological association between LSTV and lumbosacral pedicle asymmetry (PA) using computed tomography (CT). METHODS: A retrospective review of CT images of 347 lumbosacral degenerative disease patients was performed. We divided the subjects into two groups: the normal and LSTV groups. LSTV was classified based on Castellvi's classification. PA was defined as a difference of more than 20° between the right and left angles of the pedicle. RESULTS: Seventy out of 347 lumbosacral degenerative disease patients (20.17%) were diagnosed with LSTV. In the normal group, only a 0.54% incidence of PA was seen; however, with respect to the LSTV group, a 9.29% incidence of PA was seen. A significant difference in PA incidence was observed between the groups (p < 0.001). Type IIIa and Type IV in the LSTV group showed a statistically significant PA incidence rate (p = 0.004 and p = 0.039, respectively). CONCLUSIONS: Our study demonstrated that there was a significant difference in the incidence of PA between LSTV subjects and normal subjects. Moreover, the incidence of PA was significantly higher in LSTV subjects with severe anomaly. These results suggested that lumbosacral spine anomaly might have a close relationship with the incidence of PA and lumbosacral nerve root asymmetry. Therefore, morphological evaluation of the pedicle is important for preoperative surgical management, especially in cases using pedicle screws. This information could lower the incidence of pedicle screw malposition when pedicle screws are inserted at the lumbosacral spine.

Does Modic Change Progresss With Age?

STUDY DESIGN: Cross-sectional imaging study. OBJECTIVE: The aim of this study was to clarify the trend in the generation distinctions about the prevalence of Modic change (MC) including elderly patients. SUMMARY OF BACKGROUND DATA: MC has been discussed regarding its clinical significance, relationship with low back pain, suitable treatments, prevalence, and natural history. However, previous reports have focused on younger subjects, with few studies conducted in elderly patients. If MC is actually a progressive condition of a patient, then it should become more common as the patient ages. We herein report the distribution of MC across several age groups. METHODS: Patients who underwent lumbar magnetic resonance imaging (MRI) in our institution from April 2013 to March 2015 were recruited. MC was assessed using T1- and T2-weighted magnetic resonance imaging (MRI) and divided into Modic types (MT) 1, 2, and 3, and mixed type. Trends in the prevalence of MC were analyzed based on age. RESULTS: We ultimately included 585 patients of an initial 937 who underwent lumbar MRI. The mean age was 65 years. MC was identified in 36.0% of the patients. The prevalence of MC by age was 0% for those in their 10 s, 10% for those in their 20 s, 33% for those in their 30 s, 27% for those in their 40 s, 32% for those in their 50 s, 44% for those in their 60 s, 42% for those in their 70 s, and 26% for those in their 80 s. By type, 3.3% were MT1, 81.3% were MT2, 0.5% were MT3, and 14.8% were mixed type. CONCLUSION: The prevalence of MC increased with age to some degree, with the highest frequency observed in individuals in their 60 s before declining in those in their 70 s and 80 s. These findings suggest that MC might not simply progress with age, particularly after the seventh decade of life. LEVEL OF EVIDENCE: 4.