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Complex regional pain syndrome (CRPS) describes an array of painful conditions that are characterized by continuing regional pain. CRPS comprises severe and inappropriate pain in cases of complete recovery after trauma. Research on the pharmacological treatment of CRPS, however, has not been well investigated. In this study, we compared the pain relief effects of different drugs (URB597, pyrrolidine dithiocarbamate, and hydralazine) in a rat model of chronic post-ischemic pain-induced CRPS. After drug injection, CRPS-induced mechanical allodynia was significantly recovered. After three repetitive drug injections, mechanical sensitivity generally improved as hyper-nociception subsided. Reduced Nav1.7 expression at dorsal root ganglions (DRGs) was observed in the drug treatment groups. Neural imaging analysis revealed decreased neural activity for each drug treatment, compared to vehicle. In addition, treatments significantly reduced IL-1β, IL-6, and TNFα expression in DRGs. These results indicated that drugs could reduce the expression of inflammatory factors and alleviate the symptoms of chronic post-ischemic pain-induced CRPS.

The brain plays important roles in mental processing and in controlling other bodily organs [...]

Background: Behçet's disease (BD) is a chronic inflammatory systemic disease that affects multiple organs. The causes of BD are still unknown, but it is primarily characterized by autoimmune reaction in the blood vessels. Current research focuses on treatments that can reduce the non-typical inflammatory responses of BD. Nevertheless, studies on improving the inflammatory effect of BD using inflammation mechanisms are still insufficient. Therefore, we conducted the integrated treatments related to inflammation modulation and achieved alleviation of symptoms in BD mice. Methods: To understand the complex etiology of BD and compare its management, the herpes simplex virus (HSV)-induced BD mouse model was used. In order to alleviate the inflammatory response in BD mice, Taraxaci Herba (TH, herbal medicine), R7050-a TNFα inhibitor, and a mixture of TH and R7050 were injected for 2 weeks repetitively. The SCORAD index was examined to evaluate the cutaneous inflammations. In addition, histological changes and inflammatory factors were analyzed. Results: Repetitive injection of TH and/or R7050 reduced the symptoms of BD and significantly decreased IL-6, IL-1β, and TNFα in blood sera. Moreover, this treatment reduced the ulcers and the deterioration of skin. Conclusions: The results of our study showed that the down-regulation of inflammatory factors is related to the control of immune responses in BD models, suggesting that a mixed drug treatment may be more effective in improving the condition of BD.

Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

Background and objectives Glial scarring and inflammation after spinal cord injury (SCI) interfere with neural regeneration and functional recovery due to the inhibitory microenvironment of the injured spinal cord. Stem cell transplantation can improve functional recovery in experimental models of SCI, but many obstacles to clinical application remain due to concerns regarding the effectiveness and safety of stem cell transplantation for SCI patients. In this study, we investigated the effects of transplantation of human mesenchymal stem cells (hMSCs) that were genetically modified to express Olig2 in a rat model of SCI. Methods Bone marrow-derived hMSCs were genetically modified to express Olig2 and transplanted one week after the induction of contusive SCI in a rat model. Spinal cords were harvested 7 weeks after transplantation. Results Transplantation of Olig2-expressing hMSCs significantly improved functional recovery in a rat model of contusive SCI model compared to the control hMSC-transplanted group. Transplantation of Olig2-expressing hMSCs also attenuated glial scar formation in spinal cord lesions. Immunohistochemical analysis showed that transplanted Olig2-expressing hMSCs were partially differentiated into Olig1-positive oligodendrocyte-like cells in spinal cords. Furthermore, NF-M-positive axons were more abundant in the Olig2-expressing hMSC-transplanted group than in the control hMSC-transplanted group. Conclusions We suggest that Olig2-expressing hMSCs are a safe and optimal cell source for treating SCI.

The anterior cingulate cortex (ACC) is a well-known brain area that is associated with pain perception. Previous studies reported that the ACC has a specific role in the emotional processing of pain. Chronic pain is characterized by long-term potentiation that is induced in pain pathways and contributes to hyperalgesia caused by peripheral nerve injury. The mammalian target of rapamycin (mTOR) signaling, which is involved in synaptic protein synthesis, could be a key factor controlling long-term potentiation in neuropathic pain conditions. Until now, there have been no reports that studied the role of mTOR signaling in the ACC involved in neuropathic pain. Therefore, this study was conducted to determine the relationship of mTOR signaling in the ACC and neuropathic pain. Male Sprague-Dawley rats were subjected to cannula implantation and nerve injury under pentobarbital anesthesia. Microinjection with rapamycin into the ACC was conducted under isoflurane anesthesia on postoperative day (POD) 7. A behavioral test was performed to evaluate mechanical allodynia, and optical imaging was conducted to observe the neuronal responses of the ACC to peripheral stimulation. Inhibition of mTOR by rapamycin reduced mechanical allodynia, down-regulated mTOR signaling in the ACC, and diminished the expressions of synaptic proteins which are involved in excitatory signaling, thereby reducing neuropathic pain-induced synaptic plasticity. These results suggest that inhibiting mTOR activity by rapamycin in the ACC could serve as a new strategy for treating or managing neuropathic pain before it develops into chronic pain.

Recent evidence indicates that motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. However, the neural mechanisms underlying the attenuated hyperalgesia after MCS are not completely understood. In this study, we investigated the neural mechanism of the effects of MCS using an animal model of neuropathic pain. After 10 daily sessions of MCS, repetitive MCS reduced mechanical allodynia and contributed to neuronal changes in the anterior cingulate cortex (ACC). Interestingly, inhibition of protein kinase M zeta (PKMζ), a regulator of synaptic plasticity, in the ACC blocked the effects of repetitive MCS. Histological and molecular studies showed a significantly increased level of glial fibrillary acidic protein (GFAP) expression in the ACC after peripheral neuropathy, and neither MCS treatment nor ZIP administration affected this increase. These results suggest that repetitive MCS can attenuate the mechanical allodynia in neuropathic pain, and that the activation of PKMζ in the ACC may play a role in the modulation of neuropathic pain via MCS.

In the pain matrix, the insular cortex (IC) is mainly involved in discriminative sensory and motivative emotion. Abnormal signal transmission from injury site causes neuropathic pain, which generates enhanced synaptic plasticity. The mammalian target of rapamycin (mTOR) complex is the key regulator of protein synthesis; it is involved in the modulation of synaptic plasticity. To date, there has been no report on the changes in optical signals in the IC under neuropathic condition after treatment with mTOR inhibitors, such as Torin1 and XL388. Therefore, we aimed to determine the pain-relieving effect of mTOR inhibitors (Torin1 and XL388) and observe the changes in optical signals in the IC after treatment. Mechanical threshold was measured in adult male Sprague-Dawley rats after neuropathic surgery, and therapeutic effect of inhibitors was assessed on post-operative day 7 following the microinjection of Torin1 or XL388 into the IC. Optical signals were acquired to observe the neuronal activity of the IC in response to peripheral stimulation before and after treatment with mTOR inhibitors. Consequently, the inhibitors showed the most effective alleviation 4 h after microinjection into the IC. In optical imaging, peak amplitudes of optical signals and areas of activated regions were reduced after treatment with Torin1 and XL388. However, there were no significant optical signal changes in the IC before and after vehicle application. These findings suggested that Torin1 and XL388 are associated with the alleviation of neuronal activity that is excessively manifested in the IC, and is assumed to diminish synaptic plasticity.

Manganese-enhanced magnetic resonance imaging (MEMRI) is based on neuronal activity-dependent manganese uptake, and provides information about nervous system function. However, systematic studies of pain processing using MEMRI are rare, and few investigations of pain using MEMRI have been performed in the spinal cord. Herein, we investigated the pain dependence of manganese ions administered in the rat spinal cord. MnCl2 was administered into the spinal cord via an intrathecal catheter before formalin injection into the right hind paw (50 μL of 5% formalin). The duration of flinching behavior was recorded and analyzed to measure formalin-induced pain. After the behavioral test, rats were sacrificed with an overdose of urethane (50 mg/kg), and spine samples were extracted and post-fixed in 4% paraformaldehyde solution. The samples were stored in 30% sucrose until molecular resonance (MR) scanning was performed. In axial Mn2+ enhancement images of the spinal cord, Mn2+ levels were found to be significantly elevated on the ipsilateral side of the spinal cord in formalin-injected rats. To confirm pain-dependent Mn enhancement in the spinal cord, c-Fos expression was analyzed, and was found to be increased in the formalin-injected rats. These results indicate that MEMRI is useful for functional analysis of the spinal cord under pain conditions. The gray matter appears to be the focus of intense paramagnetic signals. MEMRI may provide an effective technique for visualizing activity-dependent patterns in the spinal cord.

Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)–scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC–scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC–scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI., Tissue engineering: Repairing brain and spinal injuries Biodegradable scaffolds seeded with human fetal brain cells can help repair neurological injuries in rodents. A team led by Kook In Park and Il-Shin Lee from the Yonsei University College of Medicine in Seoul, South Korea, created a mesh of plastic fibers that they bathed in neural progenitor cells. Over the course of several days, these cells differentiated into different types of brain cells, including neurons and glia. The researchers implanted these cell-scaffold complexes into the sites of injury in two rodent models: newborn mice with oxygen deprivation to the brain, and adult rats with severed spinal cords. In both cases, the treatment helped the injured tissues heal and improved the neurological or motor function of the animals. The authors suggest these tissue-engineered structures could also help people with brain or spine injuries.

Spinal cord injury (SCI) disrupts neuronal networks of ascending and descending tracts at the site of injury, leading to a loss of motor function. Restoration and new circuit formation are important components of the recovery process, which involves collateral sprouting of injured and uninjured fibers. The present study was conducted to determine cortical responses to antidromic stimulation of the corticospinal tracts, to compare changes in the reorganization of neural pathways within normal and spinal cord-injured rats, and to elucidate differences in spatiotemporal activity patterns of the natural progression and reorganization of neural pathways in normal and SCI animals using optical imaging. Optical signals were recorded from the motor cortex in response to electrical stimulation of the ventral horn of the L1 spinal cord. Motor evoked potentials (MEPs) were evaluated to demonstrate endogenous recovery of physiological functions after SCI. A significantly shorter N1 peak latency and broader activation in the MEP optical recordings were observed at 4 weeks after SCI, compared to 1 week after SCI. Spatiotemporal patterns in the cerebral cortex differed depending on functional recovery. In the present study, optical imaging was found to be useful in revealing functional changes and may reflect conditions of reorganization and/or changes in surviving neurons after SCI.

Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin into the IC on postoperative days (PODs) 3 and 7. Optical recording was conducted to observe the neural responses of the IC to peripheral stimulation. Rapamycin reduced mechanical allodynia and downregulated the expression of postsynaptic density protein 95 (PSD95), decreased neural excitability in the IC, thereby inhibiting neuropathic pain-induced synaptic plasticity. These findings suggest that mTOR signaling in the IC may be a critical molecular mechanism modulating neuropathic pain.

Background Peripheral nerve injury causes physiological changes in primary afferent neurons. Neuropathic pain associated with peripheral nerve injuries may reflect changes in the excitability of the nervous system, including the spinothalamic tract. Current alternative medical research indicates that acupuncture stimulation has analgesic effects in various pain symptoms. However, activation changes in the somatosensory cortex of the brain by acupuncture stimulation remain poorly understood. The present study was conducted to monitor the changes in cortical excitability, using optical imaging with voltage-sensitive dye (VSD) in neuropathic rats after electroacupuncture (EA) stimulation. Methods Male Sprague–Dawley rats were divided into three groups: control (intact), sham injury, and neuropathic pain rats. Under pentobarbital anesthesia, rats were subjected to nerve injury with tight ligation and incision of the tibial and sural nerves in the left hind paw. For optical imaging, the rats were re-anesthetized with urethane, and followed by craniotomy. The exposed primary somatosensory cortex (S1) was stained with VSD for one hour. Optical signals were recorded from the S1 cortex, before and after EA stimulation on Zusanli (ST36) and Yinlingquan (SP9). Results After peripheral stimulation, control and sham injury rats did not show significant signal changes in the S1 cortex. However, inflamed and amplified neural activities were observed in the S1 cortex of nerve-injured rats. Furthermore, the optical signals and region of activation in the S1 cortex were reduced substantially after EA stimulation, and recovered in a time-dependent manner. The peak fluorescence intensity was significantly reduced until 90 min after EA stimulation (Pre-EA: 0.25 ± 0.04 and Post-EA 0 min: 0.01 ± 0.01), and maximum activated area was also significantly attenuated until 60 min after EA stimulation (Pre-EA: 37.2 ± 1.79 and Post-EA 0 min: 0.01 ± 0.10). Conclusion Our results indicate that EA stimulation has inhibitory effects on excitatory neuronal signaling in the S1 cortex, caused by noxious stimulation in neuropathic pain. These findings suggest that EA stimulation warrants further study as a potential adjuvant modulation of neuropathic pain.

The insular cortex (IC) is a pain-related brain region that receives various types of sensory input and processes the emotional aspects of pain. The present study was conducted to investigate spatiotemporal patterns related to neuroplastic changes in the IC after nerve injury using voltage-sensitive dye imaging. The tibial and sural nerves of rats were injured under pentobarbital anesthesia. To observe optical signals in the IC, rats were re-anesthetized with urethane 7days after injury, and a craniectomy was performed to allow for optical imaging. Optical signals of the IC were elicited by peripheral electrical stimulation. Neuropathic rats showed a significantly higher optical intensity following 5.0mA electrical stimulation compared to sham-injured rats. A larger area of activation was observed by 1.25 and 2.5mA electrical stimulation compared to sham-injured rats. The activated areas tended to be larger, and the peak amplitudes of optical signals increased with increasing stimulation intensity in both groups. These results suggest that the elevated responsiveness of the IC to peripheral stimulation is related to neuropathic pain, and that neuroplastic changes are likely to be involved in the IC after nerve injury.

This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free drop contusion at the T9 level. The SCI rats were then classified into three groups; MSCs, NMSCs, and phosphate-buffered saline (PBS)-treated groups. The cells or PBS were administrated 1 week after SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scores were measured at 1-week intervals for 9 weeks. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were also recorded 8 weeks after transplantation. While transplantation of MSCs led to a clear tendency of motor recovery, NMSC-treated rats had significantly improved BBB scores and showed significantly shortened initial latency, N1 latency, and P1 latency of the SSEPs compared to PBS controls. In addition, 5-bromo-2-deoxyuridine (BrdU)-prelabeled MSCs costained for BrdU and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) were found rostrally and caudally 5 mm each from the epicenter of the necrotic cavity 4 weeks after transplantation. These results suggest that neurally differentiated cells might be an effective therapeutic source for functional recovery after SCI.

Bae Hwan Lee, Minjee Kwon, Ran Won Department of Physiology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea bhlee@yuhs.ac; mjkwon486@yuhs.ac Department of Biomedical Laboratory Science, Division of Health Sciences, Dongseo University, 47 Jurye-ro, Sasang-gu, Busan 47011, Republic of Korea wonran@gdsu.dongseo.ac.kr

Optical imaging techniques have made it possible to monitor neural activity and to determine its spatiotemporal patterns. Traumatic spinal cord injury (SCI) results in both the death of gray matter neurons and the disruption of ascending and descending white matter tracts at the injury site, leading to the loss of motor and sensory functions. In this study, we monitored and compared cortical responses to the stimulation of sensory tracts in normal control and spinal-cord-injured rats using an optical imaging technique based on a voltage-sensitive dye (VSD). The sciatic nerve was stimulated with a platinum bipolar electrode, and the exposed cortical surface was stained with Di-2-ANEPEQ. Optical signals were recorded from the cerebral cortex using the MiCAM02 optical imaging system. Characteristic spatiotemporal patterns were observed in response to electrical stimulation of the sciatic nerve in normal control rats. In spinal-cord-injured rats, the optical signals were dramatically reduced compared to those of normal rats. Four weeks after SCI, however, the activation area increased in the vicinity of the focal sensory area compared to that of the rats 1 week after SCI. These results suggest that optical imaging with VSD may be useful to map functional changes after SCI.

This study was conducted to whether the administration of mexiletine, a Na+ channel blocker, impacts the recovery from demyelination. Under anesthesia, 0.1% ethidium bromide was injected into the dorsal funiculus (T3), followed by a mexiletine or saline treatment. Motor evoked potential (MEP) recordings and luxol fast blue stainings were performed at one, seven, 14, and 21 days post-operatively. Conduction was delayed during demyelination, but the mexiletine-injected group demonstrated shortened latencies and reductions in the demyelination area when compared to the control. These results suggest that systemic mexiletine plays a positive role in protecting neural tissues from demyelination.

Optical imaging technique enables the recording of cortical activities in multiple sites of the primary somatosensory cortex in real time. The present study was aimed to visualize neural activity in response to the acupuncture stimulation in the rodent primary somatosensory cortex by a high-resolution optical imaging system using voltage-sensitive dyes.Optical imaging was exploited to examine the temporal-spatial characteristic of rat primary somatosensory cortex during electroacupuncture stimulation (6 mA intensity and 2 ms duration) at two pairs of acupuncture points (ST36-SP6 or GB34-BL57).In terms of magnitude and duration of the optical response, there was no difference between ST36-SP6 and GB34-BL57 stimulations. Maximally activated sites by electroacupuncture stimulation to the different acupuncture points were spatially differentiated in rat primary somatosensory cortex.The results indicate that neuronal responses to electroacupuncture stimulation can be visualized in rat primary somatosensory cortex using an optical imaging system. The topographical mapping of acupuncture points in primary somatosensory cortex will make a significant contribution to the understanding of neural mechanisms of the acupuncture treatment and Meridian phenomena.

To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury.Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord.Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment.These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

The insular cortex is an important region of brain involved in the processing of pain and emotion. Recent studies indicate that lesions in the insular cortex induce pain asymbolia and reverse neuropathic pain. Endogenous cannabinoids (endocannabinoids), which have been shown to attenuate pain, are simultaneously degraded by fatty acid amide hydrolase (FAAH) that halts the mechanisms of action. Selective inhibitor URB597 suppresses FAAH activity by conserving endocannabinoids, which reduces pain. The present study examined the analgesic effects of URB597 treatment in the insular cortex of an animal model of neuropathic pain. Under pentobarbital anesthesia, male Sprague–Dawley rats were subjected to nerve injury and cannula implantation. On postoperative day 14, rodents received microinjection of URB597 into the insular cortex. In order to verify the analgesic mechanisms of URB597, cannabinoid 1 receptor (CB1R) antagonist AM251, peroxisome proliferator-activated receptor alpha (PPAR alpha) antagonist GW6471, and transient receptor potential vanilloid 1 (TRPV1) antagonist Iodoresiniferatoxin (I-RTX) were microinjected 15 min prior to URB597 injection. Changes in mechanical allodynia were measured using the von-Frey test. Expressions of CB1R, N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), and TRPV1 significantly increased in the neuropathic pain group compared to the sham-operated control group. Mechanical threshold and expression of NAPE-PLD significantly increased in groups treated with 2 nM and 4 nM URB597 compared with the vehicle-injected group. Blockages of CB1R and PPAR alpha diminished the analgesic effects of URB597. Inhibition of TRPV1 did not effectively reduce the effects of URB597 but attenuated expression of NAPE-PLD compared with the URB597-injected group. In addition, optical imaging demonstrated that neuronal activity of the insular cortex was reduced following URB597 treatment. Our results suggest that microinjection of FAAH inhibitor into the insular cortex causes analgesic effects by decreasing neural excitability and increasing signals related to the endogenous cannabinoid pathway in the insular cortex.

Using lumbar 5 (L5) dorsal root rhizotomy-bearing rats, we examined the extent to which L5 spinal nerve lesion (SNL)-induced mechanical hyperalgesia was governed by two peripheral components, that is Wallerian degeneration (WD) and peripherally-propagating injury discharge (PID). The contribution of WD to SNL-induced hyperalgesia was studied by excluding PID with lidocaine treatment that blocked nerve conduction temporarily, but completely at the time of injury, whereas PID was examined separately by using brief tetanic electrical stimulation of the spinal nerve mimicking PID. Following the disappearance of L5 rhizotomy-induced transient hyperalgesia, L5 SNL resulted in long-lasting mechanical hyperalgesia as early as one day post-SNL despite a PID block, highlighting the role of WD. In a comparative experiment, a delayed onset of hyperalgesia (7 days) was measured in L3 rhizotomy-bearing rats following L3 SNL with a PID block, in which injured fiber (L3) was separated from intact fibers (L4 and L5) anatomically until they meet at the peripheral terminals, supporting the importance of interactions between degenerating and adjacent intact fibers for WD-induced hyperalgesia. Tetanic electrical stimulation of decentralized L5 spinal nerve resulted in mechanical hyperalgesia developing within 1 day and persisting for 7 days. This hyperalgesia was prevented by lidocaine blockade of the L5 nerve, and was unaffected by lidocaine blockades of the central inputs from L3 and L4 fibers during L5 nerve stimulation, suggesting the mediation of PID-induced hyperalgesia by sensitization, not activation, of peripheral terminals of adjacent intact afferents. The similar hyperalgesia was also observed following electrical stimulation of decentralized L3 spinal nerve. Prior elimination of L4 C-fibers by local capsaicin prevented hyperalgesia induced either by L5 SNL with a PID block or by L5 nerve stimulation. These results suggest that neighboring C-afferents remaining intact after partial nerve injury play a critical role in the development of mechanical hyperalgesia through interaction with degenerating afferents, and also via peripheral sensitization by PID.

This study was conducted to examine the role of galanin and neuropeptide Y (NPY) in the modulation of neuropathic pain at the level of the medulla. Under pentobarbital anesthesia, Sprague-Dawley rats were subjected to neuropathic surgery. Intracisternal injections of galanin and NPY were performed 2 weeks after nerve injury and mechanical allodynia was monitored. In an electrophysiological experiment, rats were reanesthetized with urethane and the responses of gracile nucleus neurons to mechanical stimulation were observed. Galanin and NPY were applied microiontophoretically. Intracisternally administered NPY reduced neuropathic pain behaviors in a dose-dependent manner. High doses of galanin inhibited neuropathic pain behaviors. Iontophoretically ejected galanin and NPY inhibited responses of gracile nucleus neurons to mechanical stimulation. These results suggest that galanin and NPY play a role in modulating neuropathic pain in the gracile nucleus of the medulla.

Umbilical cord blood (UCB) is known to have stem/progenitor cells. We earlier showed that novel progenitors could be isolated from cryopreserved human UCB with high efficiency. The multipotent progenitor cells were induced to differentiate into neural-lineage cells under the appropriate condition. In this study, we confirmed these neurally induced progenitor cells (NPCs), containing higher quantities of nerve growth factor, promoted functional recovery in rats with spinal cord injury (SCI). Sprague-Dawley rats with SCI achieved a modest improvement in locomotor rating scale until 10 weeks after transplantation of the NPCs. SCI rats treated with NPCs also showed somatosensory-evoked potentials were recovered, and grafted cells especially exhibited oligodendrocytic phenotype around the necrotic cavity. These findings suggest that UCB-NPCs might be a therapeutic resource to repair damaged spinal cords.

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ(PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζin the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. Afterζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ(p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζwere decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζand that ZIP has potential applications for relieving chronic pain.

We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats.

Neuropathic pain syndromes resulted from peripheral nerve injury appear to be resistant to conventional analgesics like opioids. However, it has been demonstrated that acupuncture including aqua-acupuncture may be effective in managing neuropathic pain. The present study was conducted to determine if bee venom injection into acupoint ihibits neuropathic pain, which is difficult to be treated by usual analgesics. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery. Two weeks after nerve injury, mechanical and cold allodynia were tested in order to evaluate the antiallodynic effects of bee venom injection into an acupoint. Intraperitoneal injection of morphine inhibited mechanical allodynia dose-dependently. Bee venom injected into Zusanli acupoint significantly inhibited mechanical and cold allodynia. These results suggest that bee venom-acupuncture as well as morphine is very effective to inhibit mechanical allodynia.

Numerous efforts have been made to maximize the efficacy of treatment for spinal cord injury (SCI). Recently, oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells have been reported to remyelinate focal areas of demyelinated spinal cord in adult rats. We conducted a study to investigate the therapeutic potential of transplantation of O-2A cells in a rat model of acute SCI. SCI was induced with an NYU Impactor at T9 of rats. O-2A cells labeled with bromodeoxyuridine (BrdU) were transplanted into sites of SCI at 1 week after the induction of SCI. At 6 weeks after cell transplantation, a behavioral test showed significant functional improvement in animals that had received O-2A-cell transplants as compared to animals given cell-culture medium alone. An electrophysiological study revealed that the transplants did not improve the amplitude or latency of somatosensory evoked potentials, but a recording of motor evoked potentials showed that the latency of these potentials in the O-2A-cell-transplant group was significantly shorter than that in the group treated with cell-culture medium. Following transplantation of BrdU-labeled O-2A cells, cells positive for BrdU were detected at and near sites of SCI. Cells labeled for both BrdU and 2',3' -cyclic nucleotide-3-phosphodiesterase were also detected, showing that the transplanted O-2A cells differentiated into oligodendrocytes. By contrast, cells labeled for BrdU and glial fibrillary acidic protein, or for neuronal nuclei antigen, were not detected. Furthermore, a tract-tracing study showed that numbers of retrogradely labeled neurons increased in areas of the brain stem after O-2A-cell transplantation. The study data showed that after being transplanted into an animal with SCI, O-2A cells migrated to the area adjacent to the site of injury and differentiated into oligodendrocytes. The behavioral test and the electrophysiological and morphological studies showed that transplantation of O-2A cells may play an important role in functional recovery and the regeneration of axons after SCI.

Methylprednisolone (MP), a glucocorticoid steroid, has an anti-inflammatory action and seems to inhibit the formation of oxygen free radicals produced during lipid peroxidation in a spinal cord injury (SCI). However, the effects of MP on the functional recovery after a SCI is controversial. The present study was conducted to determine the effects of MP on the recovery of neural conduction following a SCI. A SCI was produced using the NYU spinal cord impactor. A behavioral test was conducted to measure neurological disorders, and motor evoked potentials (MEPs) were recorded. According to the behavioral test, using BBB locomotor scaling, MP-treated animals showed improved functional recoveries when compared to salinetreated animals. MEP latencies in the MP-treated group were shortened when compared to those in the control group. Peak amplitudes of MEPs were larger in the MP-treated group than those in the control group. The thresholds of MEPs tended to be lower in the MP-treated group than those in the control group. These results suggest that MP may improve functional recovery after a SCI.

A wide variety of treatment regimens have been advocated for dissections involving the intracranial arteries. Recently, the stent can be used to exclude the aneurysm from the circulation and preserve the parent artery. We evaluated the safety and efficacy of stent angioplasty for intracranial arterial dissections.Ten patients with spontaneous dissections, nine vertebral artery and one internal carotid artery lesions underwent endovascular treatment using stent placement as primary treatment modality. One stent placement was attempted in five patients initially. Three patients were intentionally treated with two overlapping stents which completely covered the aneurysm orifice. Two tandem stents were used in one patient to allow spanning the entire length of the dissection. Stent-assisted coil embolization was performed in one patient.Of the 10 patients in whom stenting was tried, the overall success in reaching the target lesion with stents was 90%. Of the 9 patients treated with stents, stent release and positioning were considered optimal in 7 patients (77.8%) and suboptimal in two. Lesions of 8 patients were improved or stable in angiographic follow-up. However, one pseudo-aneurysm was enlarged, and subsequently, was treated by proximal occlusion using coils. There were no instances of postprocedural ischaemic attacks, new neurological deficits, and no new minor or major strokes prior to patient discharge. All parent arteries of the patient who underwent the successful procedure were preserved. On the modified Rankin scale used for the follow up, all patients were assessed as functionally improved or of stable clinical status.The success in reducing dissection-induced stenosis or pseudo-aneurysm, the patency rate obtained at follow-up, and the lack of strokes (ischaemic or haemorrhagic) suggest that stent placement offers a viable alternative to complex surgical procedures or deconstructive procedures. The long-term efficacy and durability of stent placement for arterial dissection remains to be determined in a large series.

Functional deficits after spinal cord injury have originated not only from the direct physical damage itself, but from the secondary biochemical and pathological changes. Apoptotic cell death has been seen around the periphery of an injured site and has been known to ultimately progress to necrosis and infarction. We have initiated the present study focusing on the role of apoptosis in the secondary injury of the brain after acute spinal cord injury (SCI), and conducted a series of experiments, the study examining the morphological changes in the brain following the spinal injury. Under pentobarbital anesthesia, male Sprague–Dawley rats were subjected to SCI model. Rats were laminectomized and SCI was induced using NYU spinal impactor at T9 segment. The behavioral test was performed. Electrophysiologically, motor evoked potentials (MEPs) were recorded. The animals were subjected to morphological study at 12, 24, 48, 72 h, and 1 week, postoperatively. Locomotor deficits were observed after SCI, and changes in the amplitudes and latencies of the MEPs were observed. The morphological changes were evidenced by terminal TUNEL staining and Calbindin-D 28K immunohistochemistry. The TUNEL-positive cells were located at the brain motor cortex after SCI. TUNEL-positive cells were seldom found 4 h after injury. In addition, Calbindin-D 28K immunoreactive neurons were observed in the motor cortex after injury. These results suggest that apoptosis may play an important role in the pathophysiology of the brain motor cortex following acute spinal cord injury and functions that were deteriorated after SCI may be related to these electrophysiological and morphological changes.

Object. The purpose of this study was to investigate the spontaneous behavioral changes and the alteration of neuronal activities in the pedunculopontine nucleus (PPN) after ipsilateral subthalamic nucleus (STN) lesioning by kainic acid in a rat parkinsonian model created by lesioning with 6-hydroxydopamine (6-OHDA). Methods. Assumptions about the mechanisms mediating the effects of lesioning of the nigrostriatal dopaminergic pathway by 6-OHDA and the effects of STN lesioning were examined behaviorally by means of apomorphine-induced rotational behavior and forepaw-adjusting steps. The authors subsequently investigated the alteration of neuronal activities in the PPN to compare them with the behavioral changes in rat parkinsonian models. Conclusions. The results demonstrated that STN lesioning induced behavioral improvement in rat parkinsonian models. This result, which confirms previously held assumptions, may account for the therapeutic effect of STN stimulation in Parkinson disease. The alteration of the neuronal activities in the PPN units also indicates that the PPN units are responsible for the improvement in motor symptoms observed after STN lesioning in rat parkinsonian models.

It has been well documented that there is opioid resistance in neuropathic pain. This indicates that the endogenous opioid system may not be involved effectively in modulating neuropathic pain. The present study sought to determine if activation of the descending pain inhibition system might produce analgesia in the animal neuropathic model we developed. Under ketamine anesthesia, male Sprague-Dawley rats were chronically implanted with stimulating electrodes in the ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of the sciatic nerve branches were severed. Pain sensitivity was measured with a von Frey filament and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain syndrome after transection of the tibial and sural nerves were tested as to the analgesic effects of ventral PAG stimulation for an additional two weeks. Electrical stimulation of the ventral PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed the antiallodynic effects of ventral PAG stimulation. These results suggest that activation of the descending pain inhibition system including the ventral PAG reduces neuropathic pain syndrome and that opiates are involved in this system.

We have previously demonstrated that electrical stimulation of the ventral periaqueductal gray matter (PAG) produced analgesia in neuropathic pain in rats. Opioids were also shown to be involved in analgesic effects. This study sought to determine whether opiates microinjected into the ventral PAG produce analgesia. Male Sprague-Dawley rats were chronically implanted with a guide cannula in the PAG under pentobarbital anesthesia and both the tibial and sural nerves were completely cut. Pain sensitivity was postoperatively measured with a von Frey filament and acetone applied to the sensitive area for I week. Opioids such as [D-Ala 2 ,N-MePhe 4 ,Gly(ol) 5 ]-enkephalin (DAMGO) and [D-Pen 2 ,D-Pen 5 ].-enkephalin (DPDPE) were injected into the PAG. DAMGO, a μ-opioid agonist, and DPDPE, a δ-opioid agonist, were highly effective in reducing neuropathic pain. These effects were reversed by naloxone. These results suggest that the neurons in the ventral PAG are activated by opioids to produce analgesia and that specific opioid receptors are involved in the descending pain inhibition system from the PAG.

The present study was conducted to develop a new animal model of neuropathic pain employing injury to the distal sciatic nerve branches. Under halothane anesthesia, the tibial, sural, and/or common peroneal nerves were injured and neuropathic pain behaviors were compared among different groups of rats. Different types of injury produced different levels of neuropathic pain. Rats with injury to the tibial and sural nerves showed the most vigorous mechanical allodynia, cold allodynia, and spontaneous pain. These neuropathic pain behaviors were not relieved by functional sympathectomy using guanethidine. The results suggested that injury to the tibial and sural nerves, while leaving the common peroneal nerve intact, can be used as a new animal model of neuropathic pain and that this model represents sympathetically independent pain (SIP). The present animal model is very simple to produce injury and can produce profound and reliable pain behaviors. These features enable the new animal model to be a useful tool in elucidating the mechanisms of neuropathic pain, especially SIP.

This study compared and contrasted the manifestation of neuropathic pain behaviors in several strains of rats. These included ACI, Brown-Norway, Fischer 344, Lewis, Long-Evans, Sprague-Dawley, and Wistar-Furth, all obtained from Harlan Sprague-Dawley Inc. Comparison was also made between two substrains of Sprague-Dawley rats: one from Harlan and the other from Sasco. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves with the animals under halothane anesthesia. Tests were conducted for 2 weeks to examine behavioral signs representing mechanical allodynia, cold allodynia, and spontaneous pain. There was no difference between strains in any of the tested behaviors before surgery. After neuropathic injury, rats in most groups developed high levels of behavioral signs of various components of neuropathic pain; however, some strains of rats showed weak behavioral signs of neuropathic pain. When a comparison was made between two substrains of Sprague-Dawley rats from two different sources, the ones from Sasco showed weaker behavioral signs than those from Harlan. When comparisons were made between different strains of rats from the same source (Harlan), Brown-Norway and Long-Evans rats showed the smallest magnitude of neuropathic pain behaviors. The data indicate that different strains and substrains of rats display different degrees of pain behaviors, suggesting that strains and substrains are important variables in the development of neuropathic pain after peripheral nerve injury.

Acupuncture is the process of stimulating skin regions called meridians or acupoints and has been used to treat pain-related symptoms. However, the pain-relieving effects of acupuncture may be different depending on acupoints. In the present study, the effects of acupuncture on behavioral responses and c-Fos expression were evaluated using a formalin test in male Sprague-Dawley rats in order to clarify the analgesic effects of three different acupoints. Each rat received manual acupuncture at the ST36 (Zusanli), SP9 (Yinlingquan) or BL60 (Kunlun) acupoint before formalin injection. Flinching and licking behaviors were counted by two blinded investigators. Fos-like immunoreactivity was examined by immunohistochemistry in the rat spinal cord. Manual acupuncture treatment at BL60 acupoint showed significant inhibition in flinching behavior but not in licking. Manual acupuncture at ST36 or SP9 tended to inhibit flinching and licking behaviors but the effects were not statistically significant. The acupuncture at ST36, SP9, or BL60 reduced c-Fos expression as compared with the control group. These results suggest that acupuncture especially at the BL60 acupoint is more effective in relieving inflammatory pain than other acupoints.

The extent of the sprouting of sympathetic postganglionic fibers in the dorsal root ganglion (DRG) and the peripheral nerves was examined in neuropathic rats at different postoperative times. After the L5 and L6 spinal nerves were ligated on one side, three different pain behavior tests (representing mechanical allodynia, cold allodynia, ongoing pain exacerbated by cold stress) were performed at various time intervals. The sympathetic postganglionic fibers were visualized by immunostaining with antibodies to tyrosine hydroxylase (TH). In the neuropathic rats, all three pain behaviors were fully developed within 3 days after the surgery, maintained up to 2 weeks, and then started to decline gradually afterward. At 20 weeks after neuropathic surgery, pain behaviors were reduced significantly compared to the peak response, but were still higher than the presurgery levels. Sympathectomy, performed 4 days after neuropathic surgery, almost completely abolished the signs of mechanical allodynia and ongoing pain behaviors, and it reduced the behaviors of cold allodynia to approximately half. The numerical density of sympathetic fibers in the DRG of an injured segment was significantly higher at 1, 4, and 20 weeks after neuropathic surgery as compared to the normal, suggesting that there is sprouting of sympathetic fibers in the DRG after peripheral nerve injury. Sprouting of sympathetic fibers in the DRG was extensive as early as 2 days after the spinal nerve ligation, and the sprouted fibers were almost completely eliminated after sympathectomy. The data suggest that sympathetic innervation of the DRG may play an important role in the development and maintenance of sympathetically maintained neuropathic pain.

Background The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. Methods Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. Results While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. Conclusion In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.

Acupuncture was used to treat symptoms of pain in the ancient orient. The present study was conducted to determine the effects of electroacupuncture (EA) at the BL60 acupoint on male Sprague-Dawley rats. Each rat received EA at BL60 acupoint before formalin injection. Behavioral responses were recorded using a video camera and c-Fos immunohistochemistry was performed thereafter. Treatment of EA at BL60 significantly inhibited flinching behavior and c-fos expression induced by formalin injection into the paw, compared to a control group. These results suggest that electroacupuncture at BL60 acupoint may be effective in relieving inflammatory pain.

The production of proinflammatory cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) plays a key role in chronic pain such as neuropathic pain. We investigated changes in cytokine expression in injured peripheral nerves and dorsal root ganglia (DRG) following electroacupuncture (EA) treatment. Neuropathic pain was induced by peripheral nerve injury to the left hind limb of Sprague-Dawley rats under pentobarbital anesthesia. Two weeks later, the nerve-injured rats were treated by EA for 10 minutes. The expression levels of IL-1β, IL-6, and TNF-αin peripheral nerves and DRG of neuropathic rats were significantly increased in nerve-injured rats. However, after EA, the cytokine expression levels were noticeably decreased in peripheral nerves and DRG. These results suggest that EA stimulation can reduce the levels of proinflamtory cytokines elevated after nerve injury.

OBJECTIVE It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a D(1) receptor agonist) and Quinpirole (a D(2) receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. RESULTS The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration ofQuinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. CONCLUSION This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of D(1) and D(2) agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D(1), D(2) selective antagonist.

The effects of acupuncture and electroacupuncture on an animal model of arthritic pain were examined. Under halothane anesthesia, arthritic pain was induced by the injection of carrageenan into the knee joint cavity of male Sprague-Dawley rats. Behavioral performance was tested before and after the termination of acupuncture or electroacupuncture. Electrophysiologically, the responses of afferents to a movement cycle were recorded before and after acupuncture or electroacupuncture. After the acupuncture procedure, the weight-bearing force of the rats was significantly improved and the neural responses to noxious movement stimulation were reduced. Electroacupuncture significantly improved weight-bearing behavior and inhibited neural responses of articular afferents to noxious stimulation. These results indicate that acupuncture and electroacupuncture may provide a potent strategy in relieving arthritic pain.

This study investigated the characteristics of the neuronal activities of the motor thalamus (Vim and Vop) in essential tremor (ET) patients, and compared the results with those of Parkinson’s disease (PD) patients. The kinetic (Ki) neurons were found mainly in the Vim, whereas the voluntary (Vo) neurons were found principally in the Vop of ET patients. The mean firing rates of the ET patients were higher than those of the PD patients. In addition, the mean firing rates of the Ki neurons of the ET patients were higher than those of the PD patients in the Vim nuclei. However, the mean firing rates of the ventralis caudalis (Vc) neurons, which respond to sensory stimulation, were similar in each group. An analysis of the incidence of bursting neurons revealed that the Vop nucleus of the ET patients had less bursting neurons than the PD patients. However, in the Vim nucleus, both groups possessed bursting neurons even though the incidence was slightly different. Tremor cells were observed less frequently in the Vim nucleus of ET patients than in the PD patients. This study demonstrated the characteristic features of the neuronal activities of ET patients compared to those of PD patients.

The aim of the present study was to investigate the alteration of neuronal activities in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), after ipsilateral STN lesioning by kainic acid in the rat hemi-parkinsonian 6-hydroxydopamine (6-OHDA) model. In various rat parkinson’s disease (PD) models, an increase in the SNpr firing rate was observed, despite the occurrence of bursting patterns, and subthalamic lesion was found to reduce the mean firing rates and the percentage of bursting neurons in the SNpr. However, the relative proportion of bursting neurons, among all GP neurons, was slightly increased as a result of the subthalamic lesion. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism behind parkinson’s disease.