1.Advances in mechanisms of treatment for spinal cord injury with lithium.
China Journal of Orthopaedics and Traumatology 2015;28(7):679-682
Spinal cord injury is a serious disabling disease caused by a series of internal and external factors in the field of orthopaedics and neuroscience, which is a big problem for doctors all over the world. Lithium has been used to treat dipolar disorder for over 100 years. It has been reported that lithium is benefit for brain neuron. The treatment effect for spinal cord injury gets more and more attention. Researches indicate that lithium is benefit for spinal cord injury by protecting neuron,reducing after-injury inflammation increasing the produce and release of neurotrophins, stimulating neurogenesis, enhancing autophagy and inhibiting apoptosis. This article summaries advances in mechanism of treatment for spinal cord injury with lithium by reviewing and analyzing researches. Therapy combined with lithium has a good application prospect.
Animals
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Apoptosis
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drug effects
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Humans
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Lithium
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therapeutic use
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Neurons
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cytology
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drug effects
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Spinal Cord Injuries
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drug therapy
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physiopathology
2.Effects of iontophoretically applied naloxone, picrotoxin and strychnine on dorsal horn neuron activities treated with high frequency conditioning stimulation in cats.
Yong JEONG ; Eun Joo BAIK ; Taick Sang NAM ; Kwang Se PAIK
Yonsei Medical Journal 1995;36(4):336-347
Transcutaneous electrical nerve stimulation(TENS), acupuncture-needling, and electroacupuncture are useful non-ablative methods in medical practice for relief of pain. These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. It is known that the mechanism of analagesic effect via these maneuvers are variable depending on the stimulating parameters. For example, the endogenous opioid system is profoundly related to the mechanism when a peripheral nerve stimulation is applied with parameters of low frequency and high intensity. However, when stimulated with parameters of high frequency and high intensity, the reduced activity of dorsal horn neurons is only slightly reversed by a systemic administration of naloxone, a specific opiate antagonist. Thus, the present study was performed to investigate the neurotransmitter that concerns the mechanism of peripheral nerve stimulation with parameters of high frequency and high intensity. We used an iontophoretic application of antagonists of possible related neurotransmitters. The dorsal horn neuron activity which was evoked by squeezing the peripheral cutaneous receptive field, was recorded as an index of pain with a microelectrode at the lumbo-sacral spinal cord. Naloxone, picrotoxin and strychnine were applied at 200nA during a period of conditioning nerve stimulation. We observed the effects of these drugs on the change of dorsal horn neuron activities. The main results of the experiment can be summarized as follows. The spontaneous activity of dorsal horn neurons increased in the presence of glutamate and decreased with GABA. It did not change with naloxone, picrotoxin or strychnine. When naloxone was applied iontophoretically during peripheral nerve stimulation, there was no statistically significant analgesic effect compared with that of the control group. When picrotoxin was applied iontophoretically during peripheral nerve stimulation, the analgesic effect was reduced. When strychnine was applied, the analgesic effect was reduced but did not show a statistically significant difference with the control group. These results suggested that the GABAergic system may have been partially related in the analgesic action of peripheral nerve stimulation with parameters of high frequency and high intensity.
Animal
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Cats
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*Conditioning (Psychology)
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Female
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Iontophoresis
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Male
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Naloxone/*pharmacology
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Neurons/drug effects
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Picrotoxin/*pharmacology
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Spinal Cord/cytology/*drug effects
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Strychnine/*pharmacology
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*Transcutaneous Electric Nerve Stimulation
3.Protective effect of glial cell line-derived neurotrophic factor infused into the tube setted into cavitas subarachnoidealis on spinal front corner motor neurons.
Shi-peng PAN ; Qiang LIU ; Dou WU
China Journal of Orthopaedics and Traumatology 2009;22(2):122-124
OBJECTIVETo investigate the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) infused into the cavitas subarachnoidealis on cornu anterius medullae spinalis motor neurons after sciatic nerve axotomy.
METHODSForty-eight healthy SD rats were divided into 2 groups randomly: GDNF group and NS group. The left sciatic nerve in rats were cut off. And then 0.9% saline (6 microl) and GDNF solution (6 microl) were injected into cavitas subarachnoidealis at L4-L6 in NS group and GDNF group,respectively. The rats were sacrificed on postoperative 1, 2, 4 and 8 weeks respectively. Their specimen of L4-L6 spinal cord were taken at different time and sectioned. The HE staining, Nissl staining and cholinesterase (ChE) staining in motor neurons were used for counting of motor neurons.
RESULTSIn GDNF group the number of motor neurons in cornu anterius medullae spinalis and the ChE activity were higher than that of NS group.
CONCLUSIONThe exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury.
Animals ; Axotomy ; Cholinesterases ; metabolism ; Glial Cell Line-Derived Neurotrophic Factor ; pharmacology ; Male ; Motor Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; cytology ; drug effects ; metabolism ; Spinal Cord ; cytology ; drug effects ; metabolism ; surgery
4.The relationship between the protection of ginsenoside for spinal cell and nitric oxide.
Shu-yi PAN ; Xiao-wen PAN ; Su-ping WANG
China Journal of Chinese Materia Medica 2003;28(9):851-853
OBJECTIVETo study the relationship between the protection of Ginsenoside(GS) for spinal cells and nitric oxide (NO).
METHODSpinal cells were cultured in vitro, the model of peripheral nerve was established by scarifying the cells, and NO was measured by Griess method.
RESULTNO in injury group was high than that in noninjury group and NO in group cultured by GS was less than that in group cultured by common medium.
CONCLUSIONNO increases when peripheral nerve is injuried, and the protective effect of GS on spinal cells may be through inhibiting NO release.
Animals ; Cells, Cultured ; Fetus ; Ginsenosides ; isolation & purification ; pharmacology ; Motor Neurons ; cytology ; drug effects ; metabolism ; Neurons, Afferent ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; metabolism ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; cytology ; metabolism
5.Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal cord neurons.
Li-ze XIONG ; Qiang WANG ; Mu-yun LIU ; Ye PENG ; Qing-bo LI ; Zhi-hong LU ; Chong LEI
Chinese Medical Journal 2007;120(22):1958-1962
BACKGROUNDOur previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model.
METHODSThe spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of beta-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine + Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay.
RESULTSThe viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P < 0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P < 0.05).
CONCLUSIONAlthough Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine-induced neurotoxicity in vitro.
Anesthetics, Local ; toxicity ; Animals ; Bupivacaine ; toxicity ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Injections ; Mice ; Neurons ; drug effects ; Spinal Cord ; cytology ; drug effects
6.Effect of shentong zhuyu decoction on pain behavior and spinal cord astrocytes model of osteocarcinoma pain.
Bing-xu REN ; Zheng-liang MA ; Yan-qing JIN
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(3):381-385
OBJECTIVETo study the analgesic effect of shentong zhuyu decoction (SZD) and its effect on the expression of the spinal cord glial fibrillary acidic protein (GFAP).
METHODSOne hundred C3H/HeNCrlVr male mice were randomly divided into the normal group (n=8), the sham operation group (n=30), the model group (n=30), the Chinese medicine (CM) group 1 (n=8), the CM group 2 (n=8), the CM group 3 (n=8), and the vehicle group (n=8). 0.1 g crude drug of SZD/0.4 mL, 0.3 g crude drug of SZD/0.4 mL, 0.9 g crude drug of SZD/0.4 mL, and 0.4 mL normal saline were respectively given by gastrogavage to mice in CM 1, 2, 3 groups and the vehicle group, once daily for seven days starting from Day 14. The paw withdrawal thermal latency (PWTL), as the behavior indicator, was assessed in mice using radiant thermal stimulator. The lumbar enlargement of the spinal cord was taken after the behavioral test on Day 21. GFAP mRNA and protein expressions were detected using real-time quantitative RT-PCR and Western blot.
RESULTSCompared with the normal group (Day 0) (PWTL: 15.91 +/- 1.65 s) and the sham operation group (PWTL: Day 4: 13.33 +/- 1.44 s; Day 7: 11.28 +/- 0.61 s; Day 10: 15.47 +/- 2.46 s; Day 14: 15.69 +/- 1.98 s; Day 21: 15.69 +/- 1.68 s), the PWTL value in the model group (Day 4: 13.24 +/- 1.02 s; Day 7: 11.30 +/- 1.09 s; Day 10: 9.12 +/- 0.54 s; Day 14: 7.79 +/- 0.77 s; Day 21: 6.36 +/- 0.59 s) progressively decreased (P < 0.05) as time went by, while the spinal cord GFAP mRNA and protein expressions gradually increased. Compared with the normal group (Day 0) and the sham operation group (Day 14), the PWTL value in the CM groups and the vehicle group obviously decreased on Day 14 (P < 0.05). The PWTL value was not significantly different among the model group, CM groups, and the vehicle group on Day 14 (P > 0.05). On Day 21 the PWTL value of CM group 2 and 3 increased and the spinal cord GFAP mRNA and protein expression levels decreased when compared with the model group and the vehicle group (P < 0.05). But no significant difference in the PWTL value or GFAP expression levels was shown among the CM 1 group, the vehicle group, and the model group (P > 0.05).
CONCLUSIONSZD had analgesic effect. Inhibition of the proliferation and activation of the spinal cord astrocytes might be one of its mechanisms.
Animals ; Astrocytes ; cytology ; drug effects ; metabolism ; Bone Neoplasms ; complications ; psychology ; Drugs, Chinese Herbal ; pharmacology ; Glial Fibrillary Acidic Protein ; metabolism ; Male ; Mice ; Mice, Inbred C3H ; Osteosarcoma ; complications ; psychology ; Pain ; etiology ; metabolism ; Spinal Cord ; cytology ; metabolism
7.Effects of mecobalamin on Bax and Bcl-2 in neurons after peripheral nerve injury.
Dongqiang WANG ; Pingping ZHANG ; Zhijun LI ; E-mail: DOCTORZHIJUN@ALIYUN.COM. ; Ying LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2015;33(11):841-843
OBJECTIVETo observe the effects of mecobalamin on the expression of apoptosis-related proteins, Bax and Bcl-2, in neurons after peripheral nerve injury, and to explore the role of neuron apoptosis in peripheral nerve regeneration after injury.
METHODSThirty healthy adult male wistar rats were randomly divided into sham-operation group, model group, and mecobalamin group, with 10 rats in each group. A rat model of left sciatic nerve semi-injury was established using forceps. Rats in the mecobalamin group were fed mecobalamin, while rats in the sham-operation group and model group were given the same dose of normal saline. The protein expression of Bax and Bcl-2 in neurons was measured at 14 days after operation. A semi-quantitative analysis of Bax and Bcl-2 proteins was performed by image analysis technology.
RESULTSThe model group had significantly increased Bax protein expression and significantly reduced Bcl-2 protein expression in spinal cord anterior horn motor neurons and ganglion sensory neurons compared with the sham-operation group (P<0.05). Compared with the model group and sham-operation group, the mecobalamin group had significantly reduced Bax protein expression and significantly increased Bcl-2 protein expression in spinal cord anterior horn motor neurons and ganglion sensory neurons (P<0.05).
CONCLUSIONMecobalamin has anti-apoptotic effect, and it contributes to neurological function recovery possibly by inhibiting the death of injured neurons.
Animals ; Apoptosis ; Male ; Neurons ; cytology ; drug effects ; Peripheral Nerve Injuries ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Wistar ; Sciatic Nerve ; pathology ; Spinal Cord ; cytology ; Vitamin B 12 ; analogs & derivatives ; pharmacology ; bcl-2-Associated X Protein ; metabolism
8.Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice.
Yingli JING ; Qingbin WU ; Xiaochen YUAN ; Bingwei LI ; Mingming LIU ; Xiaoyan ZHANG ; Shuying LIU ; Hongwei LI ; Ruijuan XIU
Chinese Medical Journal 2014;127(15):2808-2813
BACKGROUNDPericytes, located on microvessels, help to maintain vascular stability and blood-brain barrier integrity. The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear. Therefore, the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.
METHODSC57BL/6 mice were randomly divided into three groups: sham group, SCI group, and melatonin group (n = 27 per group). Functional recovery was evaluated using the Basso Mouse Scale. Motor neurons were observed using hematoxylin and eosin staining. Pericyte coverage was analyzed using immunofluorescence. Permeability of blood-spinal cord barrier (BSCB) was assessed by administration of Evan's Blue. Protein levels of occludin, aquaporin-4 (AQP4), angiopoietin-1 (Ang1), intercellular cell adhesion molecule-1 (ICAM-1), Bcl-2, and Bax were determined using Western blotting. Mimicking the pathological conditions of SCI, melatonin-treated primary pericytes were subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay, and the expression of ICAM-1 was detected by immunofluorescence.
RESULTSMelatonin treatment improved locomotor functional outcome and rescued motor neurons. Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury. The permeability of BSCB and loss of occludin were attenuated, and edema formation and upregulation of AQP4 were inhibited, after melatonin treatment. The expression of Ang1 and Bcl-2 was improved, while the expression of ICAM-1 and Bax was inhibited, in melatonin-treated SCI mice. Furthermore, the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.
CONCLUSIONSMelatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI, which might be mediated by increased pericyte coverage. The upregulation of Ang1 in pericytes could inhibit inflammation and apoptosis to protect the microvessels.
Angiopoietin-1 ; metabolism ; Animals ; Enzyme-Linked Immunosorbent Assay ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Melatonin ; pharmacology ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Microvessels ; cytology ; Occludin ; metabolism ; Pericytes ; drug effects ; metabolism ; Random Allocation ; Spinal Cord Injuries ; drug therapy ; metabolism
9.Depressant effect of Lithium on apoptosis of nerve cells of adult rats after spinal cord injury.
Fang WANG ; Chao ZHOU ; Zheng-Chao GAO ; Yu-Huan LI ; Wen-Long YANG ; Dong WANG ; Hao-Peng LI ; Xi-Jing HE
China Journal of Orthopaedics and Traumatology 2018;31(4):379-385
OBJECTIVETo study whether lithium agent produces neuroprotective effect by inhibiting the nerve cell apoptosis of rats after spinal cord injury.
METHODSForty-two male SD rats weighing 200 to 250 g were randomly divided into 3 groups: blank control group(=6) without surgery, normal saline(NS) group(=18) with intraperitoneal injection of NS (40 mg/kg); and Lithium chloride (Licl) group (=18) with intraperitoneal injection of Licl (40 mg/kg). After Allen method modeling, Licl group started intraperitoneal injection of Licl solution (40 mg·kg⁻¹·d⁻¹) within 15 min after operation to the second week. NS group, during the same interval, was injected with a same amount of NS. Postoperative 3, 7, 14 d, BBB scores in each group were measured;the expression of Bcl-2 and Bax protein were observed by immunohistochemisty staining;TUNEL staining was used to observe the nerve cell apoptosis.
RESULTSThe BBB scores in blank control group were 21. Postoperative 7, 14 d, BBB scores of Licl group were higher than that of NS group(<0.05). As for the Bcl-2 protein expression, black control group has a level of 0.081±0.003;7 d and 14 d postoperatively, the level in Licl group was 0.151±0.003, 0.163±0.003 and in NS group, 0.143±0.003, 0.154±0.002, respectively. Licl group showed significantly increased Bcl-2 protein expression(<0.05). As for the Bax protein expression, black control group showed a level of 0.071±0.003; 7 d and 14 d postoperatively, the level in Licl group was 0.121±0.002, 0.106±0.002 and in NS group was 0.126±0.001, 0.120±0.002, respectively. The Bax protein expression is significantly inhibited in the Licl group(<0.05). In nerve cell apoptosis by TUNEL staining, the positive cells were fewer in the black control group with apoptosis index (AI) of 1.98±0.19;while 7d and 14d postoperatively, the AI of Licl group was 13.12±0.69, 4.29±1.00 and of NS group, 18.26±0.87, 5.48±0.70, respectively. Licl group showed significant inhibition of the cell apoptosis(<0.05).
CONCLUSIONSLicl can promote the Bcl-2 protein expression and inhibit the Bax proteins expression in nerve cells of rat after SCI, thereby playing a role in the inhibition of nerve cell apoptosis. This may be one of the mechanisms that Licl can promote the recovery of motor function of rats after SCI.
Animals ; Apoptosis ; Lithium ; pharmacology ; Male ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; bcl-2-Associated X Protein ; metabolism
10.Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.
Rou-Gang XIE ; Yong-Jing GAO ; Chul-Kyu PARK ; Ning LU ; Ceng LUO ; Wen-Ting WANG ; Sheng-Xi WU ; Ru-Rong JI
Neuroscience Bulletin 2018;34(1):13-21
Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2) neurons. CCL2 increased NMDA-induced currents in CCR2/VGLUT2 neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.
Animals
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Benzoxazines
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pharmacology
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therapeutic use
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Chemokine CCL2
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antagonists & inhibitors
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genetics
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metabolism
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pharmacology
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Excitatory Amino Acid Agents
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pharmacology
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Excitatory Amino Acid Agonists
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pharmacology
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Female
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Freund's Adjuvant
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toxicity
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Hyperalgesia
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chemically induced
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metabolism
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prevention & control
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Long-Term Potentiation
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drug effects
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physiology
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Luminescent Proteins
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genetics
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metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Myelitis
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chemically induced
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drug therapy
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metabolism
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Neurons
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drug effects
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Pain Management
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Somatostatin
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genetics
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metabolism
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Spinal Cord
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cytology
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Spiro Compounds
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pharmacology
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therapeutic use
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Vesicular Glutamate Transport Protein 2
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genetics
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metabolism
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Vesicular Inhibitory Amino Acid Transport Proteins
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genetics
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metabolism