Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study.

BACKGROUND: Previous observational studies focused on the association of coffee consumption and neurological disease. However, it is not known whether these associations are causal. METHODS: We used Mendelian randomization (MR) study to assess the causal relationship of coffee intake with the risk of neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, and migraine. Single-nucleotide polymorphisms (SNPs) which had genetic statistical significance with coffee intake were used as instrumental variable (IV). Genetic instruments were stretched from the MRC-IEU (MRC Integrative Epidemiology Unit) analysis on the UK Biobank. We performed MR analyses using the inverse variance weighted (IVW) method as the main approach. Sensitivity analyses were further performed using MR-Egger and MR-PRESSO to assess the robustness. RESULTS: In the MR analysis, 40 SNPs were selected as IV, the F statistics for all SNPs ranged from 16 to 359. In IVW approach, our results provide genetic evidence supporting a potential causal association between coffee intake and a lower risk of migraine (OR = 0.528, 95% CI = 0.342-0.817, P = 0.004) and migraine with aura (OR = 0.374, 95% CI = 0.208-0.672, P = 0.001). However, we found no significant association between coffee intake and other neurological diseases along with their subtypes in this MR study. CONCLUSION: Using genetic data, our MR study found significant evidence supporting a causal association between coffee intake and migraine. This suggests that coffee consumption is likely a trigger or a prevention strategy for migraine.

Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

Low-Dose Collagenase Chemonucleolysis Combined with Radiofrequency in the Treatment of Lumbar Disc Herniation: A 10-Year Retrospective Study.

OBJECTIVE: This study explored the 10-year efficacy, safety, and prognostic factors of low-dose collagenase chemonucleolysis (CCNL) combined with radiofrequency (RF) in the treatment of lumbar disc herniation (LDH). METHODS: The data of 167 LDH patients were collected. Modified MacNab criteria, Numerical Rating Scale (NRS), and Japanese Orthopedic Association (JOA) scores were, respectively, used to evaluate patients' excellent and good rates, pain degree, and nerve function. The preoperative and 10-year postoperative patients' pain, numbness, and muscle weakness were compared. Patients' complications in perioperative period, recurrent/reappeared LDH, and reoperations were recorded. Finally, the independent risk factors affecting the long-time efficacy were assessed. RESULTS: A total of 126 patients were included. The patients' excellent and good rates were 86.51%-92.86% with no significant difference (P > 0.05). Postoperative NRS and JOA scores significantly improved (P < 0.01), most obvious within 6 months postoperatively. At 10 years postoperatively, 65.08%, 83.95%, and 93.02% of patients' pain, numbness, and muscle weakness were completely relieved (P < 0.05). Perioperative complications occurred in three patients with the rate of 2.38%. Recurrent/reappeared LDH patients were 11 with the ratio of 8.73%; nine of them underwent reoperations with the rate of 7.14%. And patients' probability of fair and poor efficacy at 10 years postoperatively with the course of disease >12 months and the responsibility disc ≥2 were, respectively, 6.005 and 4.227 times that of patients with the course of disease ≤12 months and the responsibility disc = 1 (P < 0.05). CONCLUSION: The combined treatment is effective and safe in the long term. A course of disease >12 months and responsibility disc ≥2 independently reduce efficacy, and a course of disease >12 months has a more significant impact.

Posterior percutaneous full-endoscopic cervical discectomy under local anesthesia for cervical radiculopathy due to soft-disc herniation: a preliminary clinical study.

The authors describe the outcomes of 25 patients, the procedure's surgical steps, and the potential advantages of using the posterior percutaneous full-endoscopic cervical discectomy under local anesthesia. They believe this technique may be a new alternative in the treatment of selected patients with cervical radiculopathy due to soft-disc herniation.

Efficacy of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis.

Spinal cord injury (SCI)­induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI­induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10­12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI­induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI­induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post­SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast­specific genes receptor activator of nuclear factor kappa­B ligand and cathepsin K were significantly upregulated and the osteoblast­specific gene core­binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI­induced osteoporosis.