Electroconvulsive Stimulation Research Articles

P.2.e.006 Synaptic and mitochondrial plasticity of the hippocampus in a genetic rat model of depression after repeated electroconvulsive seizures

Electroconvulsive therapy (ECT) has therapeutic effects on refractory depression and schizophrenia, although its biological mechanisms are still unclear. Recent studies in rodents suggest that electroconvulsive stimulation-induced seizures (ECSs) influence hippocampal adult neurogenesis, which has gained considerable traction as a possible cellular substrate for the treatment of depression. The aim of this study is to explore alteration of neurogenesis in the hippocampus following ECSs and the relationship between neurogenesis and behavior in rats. In the present study, we administered a single or 10-repeated application of electroconvulsive stimulations that reliably resulted in seizure (an animal model of electroconvulsive therapy) to rats. Then cell proliferation of newborn cells in the subgranular zone (SGZ) of the dentate gyrus (DG) was investigated 3 and 14 days after ECS treatments. Cell differentiation was also examined 4 weeks after newly formed cells were confirmed. As a result, ECS-induced cell proliferation in the hippocampus showed biphasic changes after ECS. The amount of cell proliferation at 3 days after the last ECS increased twice as much as the sham group. However, the number of proliferating cells at 14 days later decreased to a half of the sham level. Differentiation of newly formed cells was not influenced in ECS-treated groups compared with sham-treated groups. In addition, we investigated the effects of ECS on behavioral changes in rats by measuring locomotor activity in an open field test and spontaneous alteration behavior in a Y-maze test. Spontaneous behavior and memory function were not influenced by repeated ECSs. These results suggest that repeated ECSs affect progenitors that have a limited ability for cell proliferation, like amplifying progenitors, to increase newly generated neurons without negative behavioral change.

P.2.f.031 Safety and effectiveness of ketamine infusions in multimodal treatment-resistant depression; naturalistic report of 16 infusions

Electroconvulsive therapy (ECT) has therapeutic effects on refractory depression and schizophrenia, although its biological mechanisms are still unclear. Recent studies in rodents suggest that electroconvulsive stimulation-induced seizures (ECSs) influence hippocampal adult neurogenesis, which has gained considerable traction as a possible cellular substrate for the treatment of depression. The aim of this study is to explore alteration of neurogenesis in the hippocampus following ECSs and the relationship between neurogenesis and behavior in rats. In the present study, we administered a single or 10-repeated application of electroconvulsive stimulations that reliably resulted in seizure (an animal model of electroconvulsive therapy) to rats. Then cell proliferation of newborn cells in the subgranular zone (SGZ) of the dentate gyrus (DG) was investigated 3 and 14 days after ECS treatments. Cell differentiation was also examined 4 weeks after newly formed cells were confirmed. As a result, ECS-induced cell proliferation in the hippocampus showed biphasic changes after ECS. The amount of cell proliferation at 3 days after the last ECS increased twice as much as the sham group. However, the number of proliferating cells at 14 days later decreased to a half of the sham level. Differentiation of newly formed cells was not influenced in ECS-treated groups compared with sham-treated groups. In addition, we investigated the effects of ECS on behavioral changes in rats by measuring locomotor activity in an open field test and spontaneous alteration behavior in a Y-maze test. Spontaneous behavior and memory function were not influenced by repeated ECSs. These results suggest that repeated ECSs affect progenitors that have a limited ability for cell proliferation, like amplifying progenitors, to increase newly generated neurons without negative behavioral change.

Book Review: Robert H. Blank. 2013. Intervention in the Brain: Politics, Policy, and Ethics. Cambridge, Massachusetts: MIT Press.

This book begins well. Blank first gives, for the benefit of lay readers and those unfamiliar with the area of neuroscience, a brief but informative description of the structure and workings of the brain itself. He then goes on to offer an overview of the current state of brain intervention ranging from direct brain intervention (electroconvulsive therapy, electronic and magnetic stimulation, psychosurgery and neural implants), psychotropic drugs, the use of virtual reality, nootropics and neurogenetics. Blank offers a concise summary and evaluation of each of these methods, outlining both potential benefits and risks. He makes the important point that most of these methods, however, do not present a cure, but rather are aimed at altering behaviour, raising the important question as the ethics of behavioural control for social convenience – particularly in relation to the vulnerable, such as the management of children with ADHD. Blank then offers a well-researched and balanced overview of the advantages and disadvantages of brain imaging techniques, and while he optimistically suggests that the accuracy and range of such technologies are rapidly improving, he does, at this point at least, concede that “science has not yet been able to produce an imaging technology that can be used to image motivation, responsibility, or propensity for behaviour” (54). Even his following discussion in Chapter Three still offers a similarly balanced discussed on some of the ethical and policy implications of such interventions, covering such areas as informed consent, whether interventions can be viewed as experimentation or therapy, issues of autonomy, authenticity, mind control, stigmatization, distributive justice and the issue of whether to act on incidental findings through brain imaging techniques. His focus is on policy within the United States, which means that not all of the issues he raises might be applicable to other medical systems, however, for the most part they can be seen as having relevancy for other nations. There is, nonetheless, animportant exception to this, which I will address later. However,itisinChapterFourwhereBlank’shitherto

P 121. Systematic review of ECT in major depressive disorder and bipolar depression during pregnancy

Background Depression, as major depressive disorder (MDD) or as bipolar depression, is frequent among pregnant women (Evans et al., 2001) and an efficient treatment is fundamental. If left untreated, there are specific risks such as preterm delivery, low birth weight, and potentially death due to acute suicidality. Treatment of depression during pregnancy supposes a great challenge for pregnant women, their partner and for physicians involved. Despite psychopharmacotherapy and psychotherapy, electroconvulsive therapy (ECT) and other brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) or vagus nerve stimulation (VNS) are current available treatment strategies to treat depressive symptoms. ECT is recommended by the American Psychiatric Association Task Force on ECT as a safe and effective treatment of depression throughout pregnancy. However, ECT during pregnancy often involves concerns by both the patient and the physician due to unsolved questions regarding safety and tolerability as well as efficacy. Method In order to retrieve insights into the frequency of reports, safety and efficacy of ECT for the treatment of MDD and bipolar depression during pregnancy we performed a systematic review of the existing literature. All publications between 1942 and the 1th December 2012 in the Medline, Embase and Scopus databases, that deal with ECT in MDD and bipolar depression during pregnancy were considered. Results N=87 cases of ECT during pregnancy (MDD n =78; bipolar depression n =9) published in n =41 articles were detected. Of these 30 were case reports and 11 case series (with reported cases between n =2 and n =16). Furthermore, we evaluated the number of reported cases between the first report in 1942 and 2012 and divided the results in 4 time periods (1942–1959 n =46, 1960–1977 n =0, 1978–1995 n =14, and 1996–2012 n =18) in order to compare reported frequency. The results of our preliminary analysis suggest that ECT is efficacious and well tolerated in mother and offspring in the majority of analysed cases. In terms of safety, the comparison of the 4 time periods revealed that in the last analyzed time period a lower complication rate was observed. Most reported adverse effects were transient confusion, memory loss, headache and very rare premature contractions (mother) and fetal bradyarrhythmias. Further parameters (e.g. outcome of follow-up investigations, applied, narcotics, gestation age at the time of ECT, mean number of ECT sessions, detailed efficacy parameters as measured by psychometric scales, changes of the frequencies of reported ECTs during pregnancy) will be presented at the congress. Conclusions Considering the results of our systematic review, ECT seems feasible in pregnant patients with MDD or bipolar depression. Our data support ECT to be more safe in the last decades for mother and offspring; however, the registered reported frequency does not support an increasingly use of this method with regard to the mentioned indication.

Electroconvulsive stimulation alters levels of BDNF-associated microRNAs

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment available yet its mechanism of action remains incompletely understood. Electroconvulsive stimulation (ECS), a rat model of electroconvulsive therapy, induces expression of brain derived neurotrophic factor (BDNF) within the brain but the precise means by which this occurs and by which it contributes to the antidepressant effects of ECS are unknown. MicroRNAs (miRNAs), a class of endogenous small non-coding RNA species, may play a role as BDNF can both regulate and be regulated by miRNAs. We examined expression of BDNF-associated miRNAs in rat brain and blood following either acute (x1) or chronic (x10) ECS. Fourteen BDNF-associated miRNA species were identified for investigation using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that levels of miRNA miR-212 were significantly increased in rat dentate gyrus following both acute and chronic ECS. MiR-212 levels also increased in whole blood following chronic ECS and this positively correlated with miR-212 levels in the dentate gyrus. Our results suggest that alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT.

Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown to reverse a depression-like state in the chronic mild stress model of depression (CMS), but the effect of ECS on cognition has not previously been investigated. In this study the CMS model was used to induce a depressive-like condition in rats. The study was designed to investigate the acute effect of ECS treatment on working memory and the chronic effect of repeated ECS treatments on depression-like behavior and working memory. The results indicated that, in the acute phase, ECS treatment induced a working memory deficit in healthy controls unexposed to stress, while repeated treatments reversed stress-induced decline in working memory, as well as recovering rats submitted to the CMS paradigm from the anhedonic-like state. Like in the clinical setting, a single ECS exposure was ineffective in inducing remission from a depression-like state.

Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis

Adult neurogenesis, the process of generating mature neurons from adult neural stem cells, proceeds concurrently with ongoing neuronal circuit activity and is modulated by various physiological and pathological stimuli. The niche mechanism underlying the activity-dependent regulation of the sequential steps of adult neurogenesis remains largely unknown. Here, we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons. Sfrp3 deletion activates quiescent radial neural stem cells and promotes newborn neuron maturation, dendritic growth, and dendritic spine formation in the adult mouse hippocampus. Furthermore, sfrp3 reduction is essential for activity-induced adult neural progenitor proliferation and the acceleration of new neuron development. Our study identifies sFRP3 as an inhibitory niche factor from local mature dentate granule neurons that regulates multiple phases of adult hippocampal neurogenesis and suggests an interesting activity-dependent mechanism governing adult neurogenesis via the acute release of tonic inhibition.

Treatment of hallucinations: A comment

We comment on a recently published article in Schizophrenia Bulletin: ‘The treatment of hallucinations in schizophrenia spectrum disorders’ (Sommer et al., 2012). Contrary to the recommendations made in this piece, we suggest that, on the basis of available evidence, psychological therapies (including, but not limited to cognitive behavioural therapy) should be proposed as a treatment of choice, medication as a possible augmentation strategy, and electroconvulsive therapy and transcranial magnetic stimulation not recommended at all.

Effects of single and repeated electroconvulsive stimulation on hippocampal cell proliferation and spontaneous behaviors in the rat

Electroconvulsive therapy (ECT) has therapeutic effects on refractory depression and schizophrenia, although its biological mechanisms are still unclear. Recent studies in rodents suggest that electroconvulsive stimulation-induced seizures (ECSs) influence hippocampal adult neurogenesis, which has gained considerable traction as a possible cellular substrate for the treatment of depression. The aim of this study is to explore alteration of neurogenesis in the hippocampus following ECSs and the relationship between neurogenesis and behavior in rats. In the present study, we administered a single or 10-repeated application of electroconvulsive stimulations that reliably resulted in seizure (an animal model of electroconvulsive therapy) to rats. Then cell proliferation of newborn cells in the subgranular zone (SGZ) of the dentate gyrus (DG) was investigated 3 and 14 days after ECS treatments. Cell differentiation was also examined 4 weeks after newly formed cells were confirmed. As a result, ECS-induced cell proliferation in the hippocampus showed biphasic changes after ECS. The amount of cell proliferation at 3 days after the last ECS increased twice as much as the sham group. However, the number of proliferating cells at 14 days later decreased to a half of the sham level. Differentiation of newly formed cells was not influenced in ECS-treated groups compared with sham-treated groups. In addition, we investigated the effects of ECS on behavioral changes in rats by measuring locomotor activity in an open field test and spontaneous alteration behavior in a Y-maze test. Spontaneous behavior and memory function were not influenced by repeated ECSs. These results suggest that repeated ECSs affect progenitors that have a limited ability for cell proliferation, like amplifying progenitors, to increase newly generated neurons without negative behavioral change.

Effects of Electroconvulsive Stimulation on Long-Term Potentiation and Synaptophysin in the Hippocampus of Rats With Depressive Behavior

To evaluate the effects of electroconvulsive stimulation (ECS) on long-term potentiation (LTP) and synaptophysin (SYP) in the hippocampus of rats under chronic unpredictable mild stress (CUMS). Sixty Sprague-Dawley rats were randomly divided into three groups (n=20 for each group): the control group (no intervention), the CUMS group (subjected to 28 days of CUMS exposure followed by 7 days of mock ECS treatment), and the CUMS+ECS group (subjected to 28 days of CUMS exposure followed by 7 days of ECS treatment). Depressive behavior was assessed by a sucrose preference test and an open-field test. The LTP levels in rat hippocampal slices were examined through electrophysiological experiments. The SYP mean density in the hippocampal CA3 region was detected by immunohistochemistry. Hippocampal SYP mRNA was assessed through reverse transcriptase-polymerase chain reaction. Chronic unpredictable mild stress diminished sucrose preference and reduced measures of locomotor activity. In addition, CUMS impaired LTP in the hippocampal CA1 region and significantly decreased SYP mean density in the hippocampal CA3 region and hippocampal SYP mRNA levels. Electroconvulsive stimulation improved these harmful behavioral effects and ameliorated LTP impairment, as well as stabilized SYP mean density in the hippocampal CA3 region and hippocampal SYP mRNA levels. These results suggest that ECS can reverse the harmful behavioral effects of CUMS in rats and that the behavioral alterations induced by ECS and/or CUMS may be associated with hippocampal neuroplasticity and SYP levels.

Epigenetic regulation of Arc and c-Fos in the hippocampus after acute electroconvulsive stimulation in the rat

Electroconvulsive stimulation (ECS) remains one of the most effective treatments of major depression. However, the underlying molecular changes still remain to be elucidated. Since ECS causes rapid and significant changes in gene expression we have looked at epigenetic regulation of two important immediate early genes that are both induced after ECS: c-Fos and Arc. We examined Arc and c-Fos protein expression and found Arc present over 4 h, in contrast to c-Fos presence lasting only 1 h. Both genes had returned to baseline expression at 24 h post-ECS. Histone H4 acetylation (H4Ac) is one of the important epigenetic marks associated with gene activation. We show increased H4Ac at the c-Fos promoter at 1 h post-ECS. Surprisingly, we also observed a significant increase in DNA methylation of the Arc gene promoter at 24 h post-ECS. DNA methylation, which is responsible for gene silencing, is a rather stable covalent modification. This suggests that Arc expression has been repressed and may consequently remain inhibited for a prolonged period post-ECS. Arc plays a critical role in the maintenance phase of long-term potentiation (LTP) and consolidation of memory in the rat brain. Thus, this study is one of the first to demonstrate DNA methylation as a regulator of ECS-induced gene expression and it provides a molecular link to the memory deficits observed after ECS.

Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

Although affective disorders have high prevalence, morbidity and mortality, we do not fully understand disease etiopathology, nor have we determined the exact mechanisms by which treatment works. Recent research indicates that intracellular calcium ion dysfunction might be involved. Here we use the chronic restraint stress model of affective disorder (6h restraint per day for 21 days) in combination with electroconvulsive stimulations to examine the effects of stress and an effective antidepressive treatment modality on L-type voltage gated calcium channel subunit mRNA expression patterns in the brain. We find that stress tended to upregulate Cav1.2 and Cav1.3 channels in a brain region specific manner, while ECS tended to normalise this effect. This was more pronounced for Cav1.2 channels, where stress clearly increased expression in both the basolateral amygdala, dentate gyrus and CA3, while stress only upregulated Cav1.3 channel expression significantly in the dentate gyrus. ECS effects on Cav1.2 channel expression were generally specific to stressed animals. Our findings are consistent with and extent previous studies on the involvement of intracellular calcium ion dysfunction in affective disorders. Selective modulation of neuronal L-type voltage gated calcium channels appears to be a promising target for the development of novel antidepressive treatment modalities.

A comparison of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour

Brief pulse electroconvulsive therapy (BP ECT; pulse width 0.5-1.5ms) is a very effective treatment for severe depression but is associated with cognitive side-effects. It has been proposed that ultrabrief pulse (UBP; pulse width 0.25-0.30ms) ECT may be as effective as BP ECT but have less cognitive effects because it is a more physiological form of neuronal stimulation. To investigate this further, we treated normal rats with a 10 session course of either BP (0.5ms), UBP (0.3ms), or sham electroconvulsive stimulation (ECS) and measured antidepressant-related changes in dentate gyrus cell proliferation and hippocampal BDNF protein levels as well as hippocampal-dependant spatial reference memory using the water plus maze and immobility time on the forced swim test. Both BP and UBP ECS induced very similar types of motor seizures. However, BP ECS but not UBP ECS treatment led to a significant, near 3-fold, increase in cell proliferation (p=0.026) and BDNF levels (p=0.01). In the forced swim test, only BP ECS treated animals had a significantly lower immobility time (p=0.046). There was a trend for similarly reduced hippocampal-dependent memory function in both BP and UBP groups but overall there was not a significant difference between treatment and control animals when tested 10 days after completing allocated treatment. These findings show that, even though both forms of ECS elicited similar motor seizures, UBP ECS was less efficient than BP ECS in inducing antidepressant-related molecular, cellular and behavioural changes.

Regulation of the galanin system in the brainstem and hypothalamus by electroconvulsive stimulation in mice

Induction of seizures by electroconvulsive stimulation (ECS) is amongst the most efficacious treatments for major depression. However, the working mechanism by which ECS exerts its antidepressant effects remains elusive. The galanin system is regulated by ECS in seizure-prone brain regions and has been shown to modulate depression-like behaviour. To further explore its potential role in the antidepressant effects of ECS the galanin system was investigated by in situ hybridisation and [(125)I]-galanin receptor binding during repeated ECS in the locus coeruleus, dorsal raphe and discrete nuclei of the hypothalamus. Adult mice were treated with ECS once daily for 14 consecutive days, a paradigm previously shown to exert antidepressant-like effects. Significant increases in galanin transcription were found in the locus coeruleus and dorsomedial nuclei of the hypothalamus. In addition, GalR2 mRNA levels in the ventro- and dorsomedial nuclei of the hypothalamus were upregulated whereas no GalR1 mRNA upregulation was observed. [(125)I]-galanin receptor binding was downregulated in the ventromedial nuclei of the hypothalamus and dorsal raphe. These data show that the galanin system is regulated by repeated ECS in brain regions involved in monoaminergic neurotransmission and stress modulation thus indicating a possible role of the galanin system in the therapeutic effects of ECS.

Time course and duration of changes in K v7.2 and K v11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations

A minimum of six electroconvulsive therapy (ECT) treatments has to be delivered to achieve sustained improvement in major depression. However, the mechanisms of the therapeutic actions of ECT are still debated. We aimed to study the time course and duration of increased Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex (Pir) after electroconvulsive stimulation (ECS). Adult male Sprague-Dawley rats received three ECS per week over 1, 2, or 3 weeks and were decapitated 3 days after the last stimulus. Additional groups of rats receiving nine ECS were sacrificed 7 or 28 days after the last ECS. In situ hybridization was used to measure Kv channel mRNA expression after ECS. Kv7.2 mRNA was increased in the hippocampus and Pir 3 days after both six and nine, but not after three ECS. This was also seen for Kv11.1 mRNA in Pir. These changes lasted for at least 7 days. These results indicate that the changes in Kv7.2 and Kv11.1 channels may contribute to the therapeutic effect of ECT. However, further research needs to be undertaken in this area to extend these findings.

Proteomic analysis of rat brains in a model of neuropathic pain following exposure to electroconvulsive stimulation

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.

Regulation of the galanin system by repeated electroconvulsive seizures in mice

Even though induction of seizures by electroconvulsive stimulation (ECS) is a treatment widely used for major depression in humans, the working mechanism of ECS remains uncertain. The antiepileptic effect of ECS has been suggested to be involved in mediating the therapeutic effect of ECS. The neuropeptide galanin exerts antiepileptic and antidepressant-like effects and has also been implicated in the pathophysiology of depression. To explore a potential role of galanin in working mechanisms of ECS, the present study examined effects of repeated ECS on the galanin system using QRT-PCR, in situ hybridization, and [(125) I]galanin receptor binding. ECS was administered to adult mice daily for 14 days, and this paradigm was confirmed to exert antidepressant-like effect in the tail suspension test. Prominent increases in galanin gene expression were found in several brain regions involved in regulation of epileptic activity and depression, including the piriform cortex, hippocampal dentate gyrus, and amygdala. Likewise, GalR2 gene expression was up-regulated in both the central and the medial amygdala, whereas GalR1 gene expression showed a modest down-regulation in the medial amygdala. [(125) I]galanin receptor binding in the piriform cortex, hippocampus, and amygdala was found to be significantly down-regulated. These data show that the galanin system is regulated by repeated ECS in a number of brain regions implicated in seizure regulation and depression. These changes may play a role in the therapeutic effect of ECS.

Changes in neuropeptide Y gene expression in the spinal cord of chronic constrictive injury model rats after electroconvulsive stimulation

Some reports have shown that electroconvulsive shock therapy (ECT) is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. We have previously shown that electroconvulsive shock (ECS) improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of these rats. In this study, we examined changes in the expression of NPY in the spinal cord of a CCI model. The rat model of CCI was established by ligating the left sciatic nerve. ECS was administered to the rats once daily for six days on days 7-12 after the operation using an electrical stimulator. RT-PCR was used to measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on the 14th day after the operation. NPY gene expression was decreased in the dorsal spinal cords after ECS; however, no differences in NPY expression were observed between the right and left side of dorsal spinal cords, suggesting that the effect of changes in NPY expression after ECS on the improvement of neuropathic pain is not directly related to the spinal cord, but mainly to the upper central nerves.

Electroconvulsive Stimulation (ECS) Increases the Expression of Neuropeptide Y (NPY) in Rat Brains in a Model of Neuropathic Pain: A Quantitative Real-Time Polymerase Chain Reaction (RT-PCR) Study

Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain. In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha1)R in the brain. After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS. Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

Commentary: “Electroconvulsive Stimulation (ECS) Increases the Expression of Neuropeptide Y (NPY) in Rat Brains in a Model of Neuropathic Pain: A Quantitative Real-Time Polymerase Chain Reaction (RT-PCR) Study,” by Okabe and Colleagues

The report by Okabe and colleagues in the current issue of Pain Medicine investigates whether electroconvulsive therapy (ECT) is useful for the treatment of neuropathic pain, using a lumbar nerve ligation model in the rat. Their methodology mimicked the clinical use of ECT in depressed patients in that treatments were administered every other day for several days. Mechanical and thermal hyperalgesia were measured daily over several days after the nerve ligation surgery and prior to ECT treatments to establish a baseline. Latency to paw withdrawal for mechanical and thermal stimuli was measured in the nerve-ligated (ipsilateral) limb and contralateral limb just prior to ECT treatments. The authors found that ECT produced antinociception to thermal stimuli in the …