Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals ; Neuralgia/genetics* ; Rats ; Signal Transduction/drug effects* ; Male ; Rats, Sprague-Dawley ; Guanine Nucleotide Exchange Factors/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Habenula/drug effects* ; Ion Channels/genetics* ; Humans

Animals ; Blood Pressure ; drug effects ; Electric Stimulation ; Female ; Habenula ; physiology ; Lidocaine ; pharmacology ; Male ; Raphe Nuclei ; physiology ; Rats ; Rats, Wistar ; Respiration ; drug effects ; Serotonin ; physiology

AIMTo investigate the effects and the possible mechanism of cocaine on the neurons of lateral habenular nucleus (LHb).

METHODSWe observed the effects on c-Fos protein expression in lateral habenular nucleus and medial habenular nucleus after injecting cocaine into a belly cavity and spontaneous and evoked discharge of pain-correlative unit through iontophoresis of cocaine into LHb. The delayed rectifier K+ current was recorded in the acute isolated LHb neuron in whole-cell mode.

RESULTS(1) The c-Fos protein expression was increased by cocaine treatment in LHb, but little effect in MHb. (2) Iontophoresis of cocaine into LHb increased the discharges of pain excitation unit and enhanced excitation response to noxious stimulation, but it decreased the discharges of pain inhibition unit and its responses to noxious stimulation in LHb. Cocaine inhibited the delayed rectifier K+ current.

CONCLUSIONCocaine can excite the LHb and increase its sensitivity. The probable mechanism is that cocaine inhibits the delayed rectifier K+ channels.

Animals ; Cocaine ; pharmacology ; Habenula ; drug effects ; metabolism ; physiology ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar

Animals ; Cocaine ; pharmacology ; Habenula ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Pain Threshold ; drug effects ; Rats

AIMThe effect and possible mechanism of Melatonin (MEL) on firing rate of pain neurons in lateral habenular nucleus of rats were investigated in the experiment.

METHODSSingle extracellular firing were recorded to study the firing rate changes of pain neurons and sensitivity changes to pain stimulation induced by MEL in LHb of rats. Reverse effect of naloxone on the analgesia induced by melatonin was also observed.

RESULTSMelatonin showed the effects on the firing of pain neurons in the LHb and decreased the sensitivity of pain neurons to pain stimulation, which could be reversed by naloxone.

CONCLUSIONMelatonin can change the responses of pain neurons to pain stimulation via opioid receptor in the LHb, which might be one of analgesic mechanisms by MEL.

Analgesics ; pharmacology ; Animals ; Habenula ; drug effects ; physiology ; Male ; Melatonin ; pharmacology ; Neuralgia ; physiopathology ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

Animals ; Habenula ; cytology ; drug effects ; Male ; Microelectrodes ; Neurons ; drug effects ; physiology ; Pain ; Pregnanolone ; pharmacology ; Rats ; Rats, Wistar

AIMTo observe the responses of pain-related neurons in habenula to the nociceptive stimuli and classic analgesic morphine for inquiring into its characteristics of pain.

METHODSThe experiment was proceeded with adult rats under light anesthetized. Through the cannula inserted by operation or the multielectrode injecting the morphine, naloxone, CCK-8 and etc into lateral cerebro-ventricule or habenula, the unit firings from the neurons of habenula were recorded.

RESULTSThe unit firings were recorded from pain-related neurons distributed in MHb or LHb. The pain-related neurons could be differentiated into pain excitatory or pain inhibitory neurons. After the morphine iontophoresed, the main response of the pain excitatory neurons was inhibited, the pain inhibitory neurons were excited. The naloxone iontophoresed could antagonize the analgesic effect of morphine on neurons of habenula. After the morphine injected (10 mg/kg, i. p) into morphine-tolerated rats, the analgesic efficacy of pain-related neurons in LHb was more stronger than in MHb. It showed that the neurons in LHb were suffered from morphine was higher than MHb. After injection of antagonist of CCK-8 into lateral cerebro-ventricle, morphine injected peritoneally could weaken the tolerance level of morphine. Conversely, after injection of morphine (10 mg/kg, i. p.) 10 min, second time injection of CCK-8 (15 ng/10 microl) into lateral cerebro-ventricle could antagonize the analgesic action of morphine on the neurons in LHb, but in MHb the antagonized action was not obviously.

CONCLUSIONThe excitatory and inhibitory neurons in Hb were sensitive to the nociceptive stimuli and not easy to adapt to it. The sensitivity of the neurons in LHb to morphine was more higher than the neurons in MHb.

Animals ; Habenula ; cytology ; drug effects ; Morphine ; pharmacology ; Naloxone ; pharmacology ; Neurons ; drug effects ; physiology ; Pain Threshold ; drug effects ; Rats ; Rats, Wistar ; Sincalide ; pharmacology

AIM AND METHODSTo investigate the effect of 2 mg/kg and 10 mg/kg losartan intraperitoneally (i.p) on arterial blood pressure (AP) and heart rate (HR) in rat and the involvement in the activity of habenulas neurons. Glass micropipette was used to record any changes of unit discharging of neurons in LHb and MHb before and after losartan was intraperitoneally injected.

RESULTSAP and HR were not significantly changed by 2 mg/kg losartan (i.p). However, AP was apparently decreased by 10 mg/kg losartan (i.p), but HR was unchanged. After 10 mg/kg losartan (i.p), 66.66% (12/18) unit discharging of neurons in LHb were increased in frequency, and 61.90% (13/21) in MHb were decreased.

CONCLUSIONAP of rat was significantly decreased by 10 mg/kg losartan (i.p). Depressor effect of losartan (i.p) was involved in the excision of neurons in LHb and the inhibition in MHb.

Animals ; Blood Pressure ; drug effects ; Habenula ; drug effects ; physiology ; Losartan ; pharmacology ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar