Objective:To observe the effects of electroacupuncture(EA)intervention on norepinephrine(NE)andα2A adrenergic receptors(α2A-R)in the dorsal root ganglion(DRG)of mice with spared nerve injury(SNI).Methods:Male C57BL/6 mice were randomly divided into sham surgery group(Sham),model group(SNI),negative control EA group(SNI+NC-EA),and EA group(SNI+EA).Mechanical and thermal stimuli were used to measure the paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL).Immunofluorescence staining was used to detect the sprouting of sympathetic nerve fibers and the co-localization of α2A-R with large-diameter sensory neurons in mouse DRG.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure NE levels in mouse serum and DRG,and Western Blot was used to detect tyrosine hydroxylase(TH)and α2A-R expression levels in DRG.Results:After SNI,the PWMT and PWTL were significantly decreased,and after electroacupuncture treatment,PWMT and PWTL were reversed and increased.Immune fluorescence staining showed that sympathetic ganglion sprouting increased in DRG after SNI,and significantly decreased after electroacupuncture;After SNI,NE,α2A-R,and TH in DRG all significantly increased,and their expression decreased after electroacupuncture intervention,but NE in the serum did not change significantly.Conclusion:In the SNI model,electroacupuncture may regulate the sympathetic-sensory coupling by inhibiting the release of NE and the expression of α2A-R in DRG,thereby producing analgesic effects.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

Decompression, Surgical ; Gout ; Humans ; Lumbar Vertebrae ; Spinal Stenosis

In order to adapt to the rapid development of brain science and cultivate high-level innovative brain science research talents, combined with the practical teaching experience in the Department of Neurobiology of Air Force Military Medical University in recent years, the article constructs a new system for fundamentals and frontiers of brain science curriculum, which integrates advanced teaching concepts, diverse teaching forms and flexible teaching modes, expecting this new curriculum system will lay a solid foundation for the cultivation of talents in brain science.

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 ; Benzoxazines ; pharmacology ; therapeutic use ; Chemokine CCL2 ; antagonists & inhibitors ; genetics ; metabolism ; pharmacology ; Excitatory Amino Acid Agents ; pharmacology ; Excitatory Amino Acid Agonists ; pharmacology ; Female ; Freund's Adjuvant ; toxicity ; Hyperalgesia ; chemically induced ; metabolism ; prevention & control ; Long-Term Potentiation ; drug effects ; physiology ; Luminescent Proteins ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelitis ; chemically induced ; drug therapy ; metabolism ; Neurons ; drug effects ; Pain Management ; Somatostatin ; genetics ; metabolism ; Spinal Cord ; cytology ; Spiro Compounds ; pharmacology ; therapeutic use ; Vesicular Glutamate Transport Protein 2 ; genetics ; metabolism ; Vesicular Inhibitory Amino Acid Transport Proteins ; genetics ; metabolism

The precise relationship between the degree of pain and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of an anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between-group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the injected paw (P< or =0.003), and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose tested (P< 0.05). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determining which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Bee Venoms ; Edema ; chemically induced ; complications ; Indomethacin ; pharmacology ; Inflammation ; chemically induced ; complications ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nociceptors ; physiology ; Pain ; etiology ; physiopathology ; Pain Measurement ; Rats ; Rats, Sprague-Dawley

By using blind spinal slice whole-cell patch-clamp technique, we observed the influence of etomidate (ET) on synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord. Male adult Sprague-Dawley rats (7~8 weeks old) were anaesthetized with urethane (1.2 g/kg, i.p.), and then lumbosacral laminectomy was performed. The lumbosacral spinal cord (L1~S3) was removed and placed in preoxygenated Krebs solution at 1~3 degrees C. After cutting all of the ventral and dorsal roots, the pia-arachnoid membrane was removed. The spinal cord was mounted on a vibrating microslicer and then a 500 microm thick transverse slice was cut. The slice was placed on a nylon mesh in the recording chamber, and then perfused at a rate of 15~20 ml/min with Krebs solution saturated with 95% O2 and 5% CO2, and maintained at 36+/-1 degrees C. Substantia gelatinosa neurons were identified by their location. Under a binocular microscope and with transmitted illumination, the substantia gelatinosa was clearly discernible as a relatively translucent band across the dorsal horn. The resistance of patch clamp electrodes was 8~12 Msigma. Signals were gained by using an Axopatch 200B amplifier with low-passfiltered at 5 kHz, and digitized at 333 kHz with an A/D converter. The results are as follows. (1) To see whether or not ET has any effects on the local miniature excitatory postsynaptic currents (mEPSC), the holding potential was set up at -70 mV. Under such a condition extracellular superfusion was made with 1 micromol/L TTX for 2 min first, which was followed by consistent application of 500 micromol/L ET and 1 micromol/L TTX for 1 min. It was shown that ET did not influence the decay time, frequency and amplitude of mEPSC, when compared to the control. (2) To see whether or not ET has any effects on the local miniature inhibitory postsynaptic currents (mIPSC) mediated by GABA(A) receptor, the holding potential was set up at 0 mV. Under this condition extracellular superfusion was made with 1 micromol/L TTX and 1 micromol/L strychnine, an antagonist of glycine receptor, for 2 min, and then with consistent application of 50 micromol/L ET, 1 micromol/L TTX and 1 micromol/L strychnine for 1 min. ET prolonged the decay time of GABAergic mIPSC by 45.57+/-12.46% (P<0.05), but did not influence the frequency and amplitude of GABAergic mIPSC, when compared with the control. (3) To see whether or not ET has any effects on the local mIPSC mediated by glycine receptor, the holding potential was also set up at 0 mV, and under this condition extracellular superfusion was made with 1 mmol/L TTX and 10 mmol/L bicuculline, an antagonist also set up at 0 mV, and under this condition extracellular superfusion was made with 1 micromol/L TTX and 10 micromol/L bicuculline, an antagonist of GABA(A) receptor, for 2 min, and then with consistent application of 50 micromol/L ET, 1 micromol/L TTX and 10 micromol/L bicuculline for 1 min. ET had no effects on decay time, frequency and amplitude of glycinergic mIPSC. The above-mentioned results show that ET plays anesthetic or analgesic roles by modulating the decay time of GABAergic mIPSC, i.e. by prolonging the mean open time of GABA(A) receptors, however, ET has no direct effect on local excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
Anesthetics, Intravenous ; pharmacology ; Animals ; Etomidate ; pharmacology ; Male ; Neurons ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA ; metabolism ; Spinal Cord ; physiology ; Substantia Gelatinosa ; physiology ; Synaptic Transmission ; drug effects