Melatonin attenuated chronic visceral pain by reducing Nav1.8 expression and nociceptive neuronal sensitization.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized in a rat model of visceral hypersensitivity induced by neonatal colonic inflammation (NCI). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for melatonin (MT) in sensitization of sodium channels in NCI rats. METHODS: Colorectal distention (CRD) in adult male rats as a measure of visceral hypersensitivity. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. Western blot and Immunofluorescence were employed to detect changes in expression of Nav1.8 and MT2. RESULTS: The results showed that rats exhibited visceral hypersensitivity after NCI treatment. Intrathecal application of melatonin significantly increased the threshold of CRD in NCI rats with a dose-dependent manner, but has no role in the control group. Whole-cell patch clamp recording showed that melatonin remarkably decreased the excitability and the density of TTX-R sodium channel in DRG neurons from NCI rats. The expression of MT2 receptor at the protein level was markedly lower in NCI rats. 8MP, an agonist of MT2 receptor, enhanced the distention threshold in NCI rats. Application of 8MP reversed the enhanced hypersensitivity of DRG neurons from NCI rats. 8MP also reduced TTX-R sodium current density and modulated dynamics of TTX-R sodium current activation. CONCLUSIONS: These data suggest that sensitization of sodium channels of colon DRG neurons in NCI rats is most likely mediated by MT2 receptor, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.

Comparison of the total and hidden blood loss in patients undergoing single-level open and unilateral biportal endoscopic transforaminal lumbar interbody fusion: a retrospective case control study.

PURPOSE: This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). METHODS: A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler's formula was employed to estimate the patient's blood volume (PBV), Gross's formula to estimate TBL, and Sehat's formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. RESULTS: TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. CONCLUSIONS: Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.

Retinoic Acid Receptor Gamma (RARγ) Promotes Cartilage Destruction through Positive Feedback Activation of NF-κB Pathway in Human Osteoarthritis.

Osteoarthritis (OA) is a severe inflammation-related disease which leads to cartilage destruction. The retinoic acid receptor gamma (RARγ) has been indicated to be involved in many inflammation processes. However, the role and mechanism of RARγ in cartilage destruction caused by inflammation in OA are still unknown. Here, we demonstrated that the RARγ was highly expressed in chondrocytes of OA patients compared with healthy people and was positively correlated with the damage degree of cartilage in OA. Cytokine TNF-α promoted the transcription and expression of RARγ through activating the NF-κB pathway in OA cartilage. In addition, the overexpression of RARγ resulted in the upregulation of matrix degradation and inflammation associated genes and downregulation of differentiation and collagen production genes in human normal chondrocyte C28/I2 cells. Mechanistically, overexpression of RARγ could increase the level of p-IκBα and p-P65 to regulate the expression of downstream genes. RARγ and IκBα also could interact with each other and had the same localization in C28/I2 cells. Moreover, the SD rats OA model induced by monosodium iodoacetate indicated that CD437 (RARγ agonist) and TNF-α accelerated the OA progression, including more severe cartilage layer destruction, larger knee joint diameter, and higher serum ALP levels, while LY2955303 (RARγ inhibitor) showed the opposite result. RARγ was also highly expressed in OA group and even higher in TNF-α group. In conclusion, RARγ/NF-κB positive feedback loop was activated by TNF-α in chondrocyte to promote cartilage destruction. Our data not only propose a novel and precise molecular mechanism for OA disease but also provide a prospective strategy for the treatment.

A new method for establishing operative channels in unilateral biportal endoscopic surgery: Technical notes and preliminary results.

BACKGROUND: The unilateral biportal endoscopic (UBE) technique has been widely used in spine surgery. At present, a traditional rigid working channel is available for the UBE system. A metal semicircular canal is located in the working channel. However, due to the metal material of the working channel, arthroscopy and instruments are constrained from moving in UBE surgery. Additionally, an assistant is needed during the procedure to hold the traditional working channel. OBJECTIVE: For simplicity of operation and convenient movement of the arthroscopy and instrument, we describe a new method for establishing operative channels in UBE surgery. METHODS: We retrospectively reviewed 50 patients who underwent unilateral biportal endoscopic discectomy (UBED) from February 2020 to August 2020 via our new method. The Oswestry Disability Index (ODI) and visual analogue scale (VAS) score were measured preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Statistical comparisons were made using analysis of covariance and paired t tests. RESULTS: The VAS scores for back pain at the five time points were 5.20 ± 2.57, 1.96 ± 0.95, 1.50 ± 0.84, 1.64 ± 1.08 and 1.18 ± 0.39. The leg pain VAS scores were 7.02 ± 2.25, 2.02 ± 1.27, 1.48 ± 0.89, 1.32 ± 0.79 and 0.88 ± 0.52. The ODI values were 51.08 ± 19.97, 19.62 ± 15.51, 8.26 ± 7.40, and 7.54 ± 6.42 to 3.24 ± 1.10. The postoperative ODIs and VAS scores of low back pain and leg pain were significantly lower than those before surgery, and differences were statistically significant (all p< 0.05). The pressure of the closed outflow was significantly higher than that of the open outflow (37.35 ± 13.11 mm Hg vs. 24.55 ± 12.64 mm Hg p= 0.003). After we tightened the infusion strap to open the outflow, the pressure decreased significantly (26.4 ± 14.08 mm Hg vs. 37.35 ± 13.11 mm Hg p= 0.015). There were 2 cases of complications, including 1 case of postoperative recurrence and 1 case of dural tears. CONCLUSION: This study demonstrates the technical feasibility, safety, and efficacy of modified channel establishment in UBE surgery.

Ankylosing spondylitis complicated with andersson lesion in the lower cervical spine: A case report.

BACKGROUND: Andersson lesion (AL) is an uncommon complication in ankylosing spondylitis (AS), which is characterized by nonneoplastic bone destruction and often appears as bone destruction and sclerosis in the vertebral body and/or the area involving the intervertebral disc. According to the literature, Andersson lesion commonly occur in the thoracic and lumbar spine and rarely in the cervical spine. CASE SUMMARY: This case involved a 78-year-old man with a long history of AS who developed AL in the cervical spine (C5/6 and C6/7). One-stage anterior-posterior approach surgery was successfully performed. At the 6-month follow-up, the pain was significantly reduced, and the limb function was gradually improved. CONCLUSION: AL uncharacteristically appears in the cervical spine and tends to be misdiagnosed as vertebral metastases or spinal tuberculosis. Posterior combined with anterior surgery achieves solid biological stabilization in the treatment of AL bone destruction.

Clinical comparison of three-dimensional exoscope vs. operative microscope in transforaminal lumbar interbody fusion: A retrospective case-control study.

Purpose: Here, we sought to determine the safety and feasibility of three-dimensional exoscope (3D EX). We compared data on surgery, complications, postoperative drainage, hematology, and clinical outcomes in the group that underwent transforaminal lumbar interbody fusion (TLIF) using an operative microscope (OM) relative to those treated using 3D EX. Methods: We retrospectively reviewed records on 74 patients who underwent one- or two-level TLIF from August 2019 to October 2020. Repeated measures analysis of variance was used to compare pre- and post-operative visual analogue scale (VAS) scores and oswestry disability index (ODI). We used analysis of covariance to compare pre- and post-operative erythrocyte count (RBC), hemoglobin (Hb), and hematocrit (Hct). Independent sample t-tests was used to compare postoperative drainage volume, total blood loss (TBL), visible blood loss (VBL) and hidden blood loss (HBL). Results: There were no significant differences in VAS and ODI scores between the two groups at all time points (all p > 0.05). RBC and HBL did not differ significantly between the two groups (all p > 0.05). There were significant differences in postoperative drainage volume,TBL, Hb, and Hct values when using 3D EX relative to OM in two-level TLIF (all p < 0.05), but not for one-level TLIF (all p > 0.05). The two groups differed significantly with regards to VBL when used for one- or two-level TLIF (all p < 0.05). Conclusion: Our data show that 3D EX is a suitable alternative to OM in TLIF. Relative to OM, 3D EX has important strengths in reducing perioperative bleeding in two-level TLIF.