Tumor necrosis factor-alpha (TNF-α) is a principal mediator in pro-inflammatory processes that involve necrosis, apoptosis and proliferation. Experimental and clinical evidence demonstrate that peripheral nerve injury results in activation and morphological changes of microglial cells in the spinal cord. These adjustments occur in order to initiate an inflammatory cascade in response to the damage. Between the agents involved in this reaction, TNF-α is recognized as a key player in this process as it not only modulates lesion formation, but also because it is suggested to induce nociceptive signals. Nowadays, even though the function of TNF-α in inflammation and pain production seems to be generally accepted, diverse sources of literature point to different pathways and outcomes. In this review, we systematically searched and reviewed original articles from the past 10 years on animal models of peripheral nervous injury describing TNF-α expression in neural tissue and pain behavior.

Lumbar disc hernia (LDH) is a leading cause of chronic pain in adults. The underlying pathology of chronic pain after discectomy remains unclear. Chronic local inflammation is considered to underlie painful symptomatology. In this context, we investigated tumor necrosis factor (TNF)-α, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2) expression at the time of surgery in LDH patients and correlated it with the severity of postoperative pain. We analyzed protein and mRNA levels from muscle, ligamentum flavum (LF), annulus fibrosus (AF), and nucleus pulposus (NP) in LDH patients and scoliosis patients (SP), who served as controls. Pain assessment with the visual analogue scale (VAS) was performed 1 day before surgery and 6 weeks and 12 months postoperatively. TNF-α protein levels were detected in AF, LF, and NP in all LDH patients, but not in SP. TNF-α mRNA was significantly greater in LDH patients than in SP; ie, 5-fold in AF, 3-fold in NP, and 2-fold in LF. For NP, TNF-α protein levels correlated with VAS scores (r=0.54 at 6-week and r=0.65 at 12-month follow-up). Also, TNFR1 protein levels in NP positively correlated with VAS scores (r=0.75 at 6-week and r=0.80 at 12-month follow-up). However, TNFR2 protein levels in AF negatively correlated with VAS scores (r=-0.60 at 6 weeks and r=-0.60 at 12 months follow-up). These data indicate that TNF-α levels could determine the clinical outcome in LDH patients after discectomy. Moreover, the opposite correlation of TNF receptors with pain sensation suggests that an unbalanced expression plays a role in the generation of pain.

Intra- and perioperatively recorded local field potential (LFP) activity of the nucleus subthalamicus (STN) has been suggested to guide contact selection in patients undergoing deep brain stimulation (DBS) for Parkinson’s disease (PD). Despite the invention of sensing capacities in chronically implanted devices, a comprehensible algorithm that enables contact selection using such recordings is still lacking. We evaluated a fully automated algorithm that uses the weighted average of bipolar recordings to determine effective monopolar contacts based on elevated activity in the beta band. LFPs from 14 hemispheres in seven PD patients with newly implanted directional DBS leads of the STN were recorded. First, the algorithm determined the stimulation level with the highest beta activity. Based on the prior determined level, the directional contact with the highest beta activity was chosen in the second step. The mean clinical efficacy of the contacts chosen using the algorithm did not statistically differ from the mean clinical efficacy of standard contact selection as performed in clinical routine. All recording sites were projected into MNI standard space to investigate the feasibility of the algorithm with respect to the anatomical boundaries of the STN. We conclude that the proposed algorithm is a first step towards LFP-based contact selection in STN-DBS for PD using chronically implanted devices.

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5–10% of the general population and up to 20–25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods.