Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation.

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

Musculoskeletal Pain during the Menopausal Transition: A Systematic Review and Meta-Analysis.

Musculoskeletal pain (MSP) is one of the most severe complaints in women undergoing menopause. The prevalence of MSP varied when taking the menopausal state and age factor into consideration. This study investigated the prevalence of MSP in perimenopausal women and its association with menopausal state. The MEDLINE, Embase, Web of Science, and PubMed databases were searched from inception to July 2020, and 16 studies were retrieved for the current meta-analysis. The primary outcome measure was the MSP Odds Ratio (OR). The estimated overall prevalence of MSP among perimenopausal women was 71% (4144 out of 5836, 95% confidence interval (CI): 64%-78%). Perimenopausal women demonstrated a higher risk for MSP than premenopausal ones (OR: 1.63, 95% CI: 1.35-1.96, P = 0.008, I 2 = 59.7%), but similar to that in postmenopausal ones (OR: 1.07, 95% CI: 0.95-1.20, P = 0.316, I 2 = 13.4%). The postmenopausal women were at a higher risk of moderate/severe MSP than the premenopausal ones (OR: 1.45, 95% CI: 1.21-1.75, P = 0.302, I 2 = 16.5%) or the perimenopausal ones (OR: 1.40, 95% CI: 1.09-1.79, P = 0.106, I 2 = 55.4%). In conclusion, the perimenopause is a state during which women are particularly predisposed to develop MSP. As to moderate to severe degrees of MSP, the odds increase linearly with age, from premenopause to peri- and then to postmenopause.

Analysis of Dynamic Plantar Pressure before and after the Occurrence of Neurogenic Intermittent Claudication in Patients with Lumbar Spinal Stenosis: An Observational Study.

Lumbar spinal stenosis (LSS) is a common disease in the elderly population; it has been reported that patients with LSS have an abnormal gait pattern due to symptom such as neurogenic intermittent claudication (NIC); however, no detailed reports exist on the plantar pressure distributions in LSS patients with NIC. To analysis the plantar pressure characteristics of LSS patients, the Footscan® pressure system was used to perform dynamic plantar pressure measurements in 20 LSS patients (age, 69.5 ± 7.2 years) before and after the occurrence of NIC. The contact time (CT), foot progression angle (FPA), pressure-time integral (PTI), and contact area (CA) were collected and compared between the LSS patients and age-matched healthy subjects in each measurement. The LSS group showed an increase in forefoot CT%, PTI, and CA% in both measurements compared with those in the control group. After the occurrence of NIC in the LSS group, CT%, PTI, and CA% of the forefoot increased further compared with those before the occurrence of NIC. In addition, after the occurrence of NIC, the PTI and CA% of the forefoot shifted from the medial foot to the lateral foot. The results suggested that the plantar pressure distributions of patients with LSS differs from normal subjects due to the posture of waking with lumbar forward flexion, and the forefoot bears a higher relative load. In addition, the occurrence of NIC could affect the plantar pressure distribution of the patients with LSS, predicting the patient's risk of falling to the anterior direction and to the symptomatic side.

Modulation of bone formation and resorption using a novel zoledronic acid loaded gelatin nanoparticles integrated porous titanium scaffold: an in vitro and in vivo study.

Osteoporotic bone defects are a major challenge in clinics for bone regeneration. With the condition of osteoporosis, excessive bone absorption and impaired osteogenesis result in unexpectedly long healing procedures for defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffold was designed, to be integrated with anti-catabolic drug zoledronic acid nanoparticles (ZOL loaded gelatin NPs), which was able to achieve a local sustained release of ZOL as expected. The in vitro study demonstrated that extracts of the composite scaffolds would stimulate osteoblast differentiation; they also inhibited osteoclastogenesis at a ZOL loading concentration of 50 µmol l-1. In the subsequent in vivo study, the composite scaffolds were implanted into ovariectomy-induced osteoporotic rabbits suffering from femoral condyles defects. The results indicated that the composite scaffolds without ZOL loaded gelatin NPs only induced callus formation, mainly at the interface margin between the implant and bone, whereas the composite scaffolds with ZOL loaded gelatin NPs were capable of further enhancing osteogenesis and bone growth into the scaffolds. Moreover, the research proved that the promoting effect was optimal at a ZOL loading concentration of 50 µmol l-1. In summary, the present research indicated that a new type of porous titanium scaffold integrated with ZOL loaded gelatin NPs inherited a superior biocompatibility and bone regeneration capability. It would be an optimal alternative for the reconstruction of osteoporosis-related defects compared to a traditional porous titanium implant; in other words, the new type of scaffold offers a new effective and practical procedure option for patients suffering from osteoporotic bone defects.

Evaluation of Anterior Decompression Surgical Outcomes of Proximal-Type Cervical Spondylotic Amyotrophy: A Retrospective Study.

OBJECTIVE: To investigate the efficiency of anterior decompression on the proximal-type cervical spondylotic amyotrophy patients. METHODS: This was a retrospective analysis. From January 2014 to November 2017, 21 patients with proximal-type cervical spondylotic amyotrophy (CSA) underwent anterior decompression. There were 15 males and 6 females, aged 35-73 years with an average of 51.62 years. All the patients underwent surgery of anterior decompression (ACDF or ACCF). Among them, 12 patients underwent C4/5 single level ACDF, eight patients underwent C4/5 and C5/6 double level ACDF, and one patient underwent C5 anterior cervical corpectomy decompression and fusion surgery. Preoperative and postoperative clinical and radiologic parameters were assessed. The clinical examinations were reviewed, including muscle strength, neck disability index (NDI) score, cervical Japanese Orthopaedic Association (JOA) score, and improvement rate of manual muscle test (MMT) at the last follow-up. Preoperative spinal cord or nerve impingement was assessed by magnetic resonance imaging (MRI) or computed tomography (CT) myelography. Postoperative lateral X-ray radiographs were performed every 3 months after the surgery. RESULTS: Severe preoperative muscle atrophy of the deltoid or biceps muscles occurred in 21 patients included in the study. All of them involve impingements of the ventral nerve root and/or the anterior horn according to MRI and CT myelography. The preoperative duration of symptoms averaged 8.4 months. The average follow-up for all patients was 13.2 months. At the final follow-up, all patients showed statistically significant improvements in muscle strength and NDI scores (P < 0.05, P < 0.05). For the deltoid muscles force and C-JOA scores, the average improvement rates were 66.49% ± 10.04% and 62.23% ± 9.23%, respectively. With respect to MMT, 12 proximal-type patients were graded excellent, six were good, and three were fair, and the overall improvement rate was 85.7%. CONCLUSIONS: For proximal-type CSA patients with cervical radiculopathy, earlier anterior decompression surgery can achieve satisfactory results by significantly improving a patient's muscle strength and relieving compression symptoms.

Clinical Investigation of the Association of Opening Size with Sagittal Canal Diameter Based on Single-Door Cervical Laminoplasty.

BACKGROUND Many clinical studies have assessed the association of laminoplasty opening size (LOS) with sagittal canal diameter (SCD) based on single-door cervical laminoplasty (SDCL). Nevertheless, the "worn-off" lamina extracted in SDCL was neglected in these reports. We aimed to develop a simple mathematical model to analyze the relationship between the effective LOS and SCD, taking into consideration the worn-off lamina. MATERIAL AND METHODS A total of 106 patients treated by SDCL at our hospital were included in this study. Pre-operative and post-operative SCDs were assessed using a picture archiving and communication system (PACS) based on computed tomography scans. Mini-plate sizes as well as drill bit diameters were recorded in detail in order to determine the effective LOS for each vertebral lamina involved. RESULTS SCD in all patients was increased significantly after SDCL (P<0.01). A linear correlation was found between effective LOS and the post-operative SCD increment from C3 to C7 (R²>0.933, P<0.001). The 12 mm mini-plate was most often used in SDCL, accounting for 64.45% of all cases, whereas 10 mm and 16 mm mini-plates were the least used, accounting for 3.85% and 3.00%, respectively. CONCLUSIONS There is a strong linear correlation between effective LOS and the post-operative SCD increment. The SCD was increased by about 0.5 mm per mm increase in effective LOS. Thus, post-operative SCD could be precisely calculated and predicted, enabling the selection of optimal mini-plate prior to SDCL.