Surgical management for chronic pain

Chronic pain in the UK affects up to 43% of the population. The consequences include physical and psychological distress, loss of function, employment, family and social strain and increased utilization of healthcare services. Modern pain management services operate across primary, secondary and tertiary care and incorporate general practitioners, psychologists, physiotherapists, pharmacists, specialist nurses, pain physicians and surgeons. This allows for a coordinated approach to chronic pain, engaging the patient in a structured pathway from conservative measures, through to surgery if necessary. Surgical interventions have been utilized effectively throughout the 20^th century for the treatment of a variety of conditions, some of which are now effectively managed with improved pharmacological approaches or novel neuromodulation techniques. Ablative procedures that aim to permanently interrupt the pain pathway still represent the final solution for some conditions, particularly those with cancer associated pain; however, the search for less invasive, less risky measures continues. This is stimulated by an increased understanding of the neurobiology of pain transmission and the physiological changes which occur in persistent pain.     

Paresthesia‐Free Spinal Nerve Root Stimulation for the Treatment of Chronic Neuropathic Pain

ObjectiveStimulation of the dorsal spinal roots, or spinal nerve root stimulation (SNRS), is a neuromodulation modality that can target pain within specific dermatomal distributions. The use of paresthesia-free stimulation has been described with conventional dorsal column spinal cord stimulation, although has yet to be described for SNRS. This objective of this study was to investigate the efficacy of paresthesia-free high-frequency (1000–1200 Hz) SNRS in the treatment of intractable, dermatomal neuropathic pain.Materials and MethodsA retrospective chart review was performed on 14 patients implanted with SNRS in varying distributions: Ten patients initially received tonic stimulation and crossed over to a paresthesia-free paradigm and four patients received only paresthesia-free stimulation. The primary outcome was reduction in pain severity (visual analog scale [VAS]), measured at baseline and follow-up to 24 months with paresthesia-free stimulation.ResultsAll 14 patients who received paresthesia-free stimulation had significant improvement in pain severity at a mean follow-up of 1.39 ± 0.15 years (VAS 7.46 at baseline vs. 3.25 at most recent follow-up, p < 0.001). Ten patients were initially treated with tonic stimulation and crossed over to paresthesia-free stimulation after a mean of 61.7 months. Baseline pain in these crossover patients was significantly improved at last follow-up with tonic stimulation (VAS 7.65 at baseline vs. 2.83 at 48 months, p < 0.001), although all patients developed uncomfortable paresthesias. There was no significant difference in pain severity between patients receiving tonic and paresthesia-free stimulation.ConclusionsWe present real-world outcomes of patients with intractable dermatomal neuropathic pain treated with paresthesia-free, high-frequency SNRS. We demonstrate its effectiveness in providing pain reduction at a level comparable to tonic SNRS up to 24 months follow-up, without producing uncomfortable paresthesias.     

Frequency of Automatic Stimulations in Responsive Vagal Nerve Stimulation in Patients With Refractory Epilepsy

BackgroundIn vagal nerve stimulation (VNS) therapy, the release of VNS model 106 (AspireSR) allowed for responsive VNS (rVNS). rVNS utilizes a cardiac-based seizure detection algorithm to detect seizure-induced tachycardia to trigger additional stimulation. There are some studies suggesting clinical benefits of rVNS over traditional VNS, but the performance and significance of autostimulation mode in clinical practice are poorly understood.ObjectivesTo assess the effect of initiation of rVNS therapy and altered stimulation settings on the number of daily stimulations and energy consumption in VNS therapy and to compare autostimulation performance in different epilepsy types.Materials and MethodsRetrospective follow-up of 30 patients with drug-resistant epilepsy treated with rVNS including 17 new implantations and 13 battery replaces at a single center in Finland. Our data consist of 208 different stimulation periods, that is, episodes with defined stimulation settings and both autostimulation and total stimulation performance-related data along with clinical follow-up.ResultsThe variation in autostimulation frequency was highly dependent on the duration of the OFF-time and autostimulation threshold (p < 0.05). There was a large additional effect of autostimulation mode on therapy time and energy consumption with longer OFF-times, but a minor effect with shorter OFF-times. Significantly more autostimulations were triggered in the temporal lobe and multifocal epilepsies than in extratemporal lobe epilepsies.ConclusionsThe initiation of autostimulation mode in VNS therapy increased the total number of stimulations. Shortening the OFF-time leads to a decreased number and share of automatic activations. Epilepsy type may affect autostimulation activity.     

使用新型倒刺电极的骶神经调节治疗神经源性膀胱的初步临床结果

目的探讨应用新型倒刺电极（Tined-lead）对神经源性膀胱患者行S骶神经调节（SNM）的初步疗效。方法对5例神经源性膀胱患者采用新型倒刺电极，在X线监测下将电极植入S3骶神经孔，进行SNM。术前、术后详细记录排尿日记，用影像尿动力学方法评估患者的膀胱尿道功能。结果患者1（隐性骶裂）术后排尿次数和排尿量分别改善22％和49％；患者2（隐性骶裂）术后排尿次数、排尿量和残余尿量分别改善0．7％、11％和46％；患者3（隐性骶裂）术后排尿次数、排尿量和残余尿量分别改善0．4％、18％和44％。患者4（脑外伤）术后漏尿次数和漏尿量分别改善36％和54％。患者5（高位截瘫）术后间歇导尿次数和导尿量分别改善42％和54％，尿动力学参数改善37％～45％。结论用新型倒刺电极进行SNM为神经源性膀胱的治疗提供了一条新的可供选择的微创方法。     

Five‐Year Follow‐up After Sacral Neuromodulation: Single Center Experience

Objective. We studied long‐term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six   months postimplant. Materials and Methods. Twenty‐two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five‐year follow‐up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six‐month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.     

Fibroblast Growth Factor Enhances Long-term Potentiation in the Hippocampal Slice

Recently we reported that perfusion of hippocampal slices with epidermal growth factor (EGF) lead to enhancement of potentiated responses after tetanic stimulation. In the present study we report that basic fibroblast growth factor (FGF) can also lead to an enhancement of potentiated responses. FGF is a mitogen for several cell types and exhibits neurotrophic effects on neurons of the central nervous system (CNS). Rat hippocampal slices were perfused with FGF at a concentration of 10-9 M. During extra- and intracellular recordings in the CA1-region, the addition of FGF to the perfusing medium produced no change in evoked responses if single pulse or paired pulse stimulation was used. Furthermore FGF had no influence on the resting membrane potential and input resistance. However, after tetanic stimulation, FGF-treated slices showed an increase in the magnitude of potentiation compared to control slices. Taken together with the EGF data these results support the hypothesis that growth factors like FGF with neurotrophic potential on CNS-neurons can influence synaptic efficacy. Furthermore these results show that factors which are able to modulate developmental plasticity and regenerative plasticity can also modulate synaptic plasticity.     

Species-specific modulation of pattern-generating circuits

Phylogenetic comparison can reveal general principles governing the organization and neuromodulation of neural networks. Suitable models for such an approach are the pyloric and gastric motor networks of the crustacean stomatogastric ganglion (STG). These networks, which have been well studied in several species, are extensively modulated by projection neurons originating in higher-order ganglia. Several of these have been identified in different decapod species, including the paired modulatory proctolin neuron (MPN) in the crab Cancer borealis [Nusbaum & Marder (1989) J. Neurosci., 9,1501-1599; Nusbaum & Marder (1989), J. Neurosci., 9, 1600-1607] and the apparently equivalent neuron pair, called GABA (gamma-aminobutyric acid) neurons 1 and 2 (GN1/2), in the lobster Homarus gammarus [Cournil et al. (1990) J. Neurocytol., 19, 478-493]. The morphologies of MPN and GN1/2 are similar, and both exhibit GABA-immunolabelling. However, unlike MPN, GN1/2 does not contain the peptide transmitter proctolin. Instead, GN1/2, but not MPN, is immunoreactive for the neuropeptides related to cholecystokinin (CCK) and FLRFamide. Nonetheless, GN1/2 excitation of the lobster pyloric rhythm is similar to the proctolin-mediated excitation of the crab pyloric rhythm by MPN. In contrast, GN1/2 and MPN both use GABA but produce opposite effects on the gastric mill rhythm. While MPN stimulation produces a GABA-mediated suppression of the gastric rhythm [Blitz & Nusbaum (1999) J. Neurosci., 19, 6774-6783], GN1/2 activates or enhances gastric rhythmicity. These results highlight the care needed when generalizing neuronal organization and function across related species. Here we show that the 'same' neuron in different species does not contain the same neurotransmitter complement, nor does it exert all of the same effects on its postsynaptic targets. Conversely, a different transmitter phenotype is not necessarily associated with a qualitative change in the way that a modulatory neuron influences target network activity.     

Accuracy of Electrode Position in Sphenopalatine Ganglion Stimulation in Correlation With Clinical Efficacy

IntroductionSphenopalatine ganglion (SPG) stimulation is an efficient treatment for cluster headache. The target for the SPG microstimulator in the pterygopalatine fossa lies between the vidian canal and foramen rotundum, ideally two contacts should be placed in this area. However, placement according to the manufacturers recommendations is frequently not possible. It is not known whether a suboptimal electrode placement interferes with postoperative outcomes.Materials and MethodsSPG stimulation was performed in 13 patients between 2015 and 2018 in a single center. Lead location was determined by intraoperative computed tomography scan and correlated with the planned lead position as well as clinical data and stimulation parameters. Patients with a reduction of 50% or more in pain intensity or frequency were considered responsive.ResultsEleven patients (84.6%) responded to SPG stimulation with eight being frequency responders (61.5%). In seven cases, there were less than two electrodes between vidian canal and foramen rotundum, there was no significant correlation with negative stimulation results (p = 0.91). The mean distance of lead location between pre- and postoperative images did not correlate with clinical outcomes (p = 0.84) and was even bigger in responders (4.91 mm vs. 4.53 mm). The closest electrode contact to the vidian canal was in the stimulation area in all but one patient, regardless of its overall distance to canal. The distance of the closest electrode to the vidian canal was, however, not significantly correlated to the percentage of frequency (p = 0.68) or intensity reduction (p = 0.61).ConclusionThere was no significant correlation regarding aberrations of lead position from the planned position with clinical outcome. However, this study might be underpowered to detect such a correlation. The closest electrode contact to the vidian canal was in the stimulation area in all but one patient in the final programming. This indicates that, overall, the lead location does play a crucial role in SPG stimulation for cluster headache.