Vascular endothelial growth factor B prevents the shift in the ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

A key model for examining the activity-dependent development of primary visual cortex (V1) involves the imbalance in activity between the two eyes induced by monocular deprivation (MD). MD early in life causes dramatic changes in the functional and structural organization of mammalian visual cortex. The molecular signals that mediate the effects of MD on the development of visual cortex are not well defined. Neurotrophic factors are important in regulating the plasticity of visual cortex, but the choice of an appropriate growth factor as well as its delivery has proven difficult. Although vascular endothelial growth factor-B (VEGF-B) is a homolog of the angiogenic factor VEGF-A, it has only minimal angiogenic activity, raising the question of whether this factor has other (more relevant) biological properties. Intrigued by the possibility that VEGF family members affect neuronal cells, we explored whether VEGF-B has a role in the nervous system. In rats, VEGF-B infusion during monocular deprivation (MD) counteracted the normally occurring ocular dominance (OD) shift toward the non-deprived eye so that the deprived eye dominated the VEGF-B-treated cortex after MD. In particular, VEGF-B counteracted the effects of MD without causing detectable alterations in spontaneous discharge or behavior. In conclusion, the simultaneous analysis of visual cortical cell discharge and ocular dominance plasticity suggests that VEGF-B has important effects on the functional architecture of the visual cortex. Therefore, VEGF-B is a new candidate trophic challenge molecule for the visual cortex.

Dopamine affects the change of pain-related electrical activity induced by morphine dependence.

Morphine is among the most effective analgesics. However, many evidences suggest that, besides the well-know analgesic activity, repeated opioids treatment can induce some side effects such as dependence, hyperalgesia and tolerance. The mechanism of noxious information transmission in the central nervous system after dependence is not clear. An important neurotransmitter, dopamine (DA) participates not only in the process of opioid dependence but also in pain modulation in the central nervous system. In the present study we observed changes of electrical activities of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the caudate nucleus (Cd) following the development of morphine dependence. We also observed the role of DA on these changes. Our results revealed that both the latency of PEN discharges and the inhibitory duration of PIN discharges decreased, and the net increased values of PEN and PIN discharges increased in the Cd of morphine dependent rats. Those demonstrated that electrical activities of both PENs and PINs increased in morphine dependent rats. DA inhibited the electrical activities of PENs and enhanced those of PINs in morphine dependent rats.

MK-801 changes the role of glutamic acid on modulation of algesia in nucleus accumbens.

Dizocilpine maleate (MK-801) causes the blockage of the glutamic acid (Glu) receptors in the central nervous system that are involved in pain transmission. However, the mechanism of action of MK-801 in pain-related neurons is not clear, and it is still unknown whether Glu is involved in the modulation of this processing. This study examines the effect of MK-801, Glu on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the nucleus accumbens (NAc) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in NAc were recorded by a glass microelectrode. Our results revealed that the lateral ventricle injection of Glu increased the discharged frequency and shortened the discharged latency of PEN, and decreased the discharged frequency and prolonged the discharged inhibitory duration (ID) of PIN in NAc of rats evoked by the noxious stimulation, while intra-NAc administration of MK-801 produced the opposite response. On the basis of above findings we can deduce that Glu, MK-801 and N-methyl-D-aspartate (NMDA) receptor are involved in the modulation of nociceptive information transmission in NAc.

Cholecystokinin-8 antagonizes electroacupuncture analgesia through its B receptor in the caudate nucleus.

OBJECTIVES: The analgesic effect of electroacupuncture (EA) stimulation has been proved. However, its mechanism of action is not clear. It has been well-known that cholecystokinin-8 (CCK-8) is a neuropeptide which is mainly related to the mediation of pain. The caudate nucleus was selected to determine if the release of CCK and the neural activity in this nucleus were involved in producing EA analgesia. MATERIALS AND METHODS: Radiant heat focused on the rat-tail was used as the noxious stimulus. The pain threshold of rats was measured by tail-flick latency (TFL). EA stimulation at the bilateral Zusanli (ST 36) acupoints of rats was used to investigate the effects of EA analgesia. The electrical activities of pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the caudate nucleus were recorded with a glass microelectrode. The present study examined the antagonistic effects of the intracerebral ventricular injection of CCK-8 on EA analgesia and reversing effects of CCK-B receptor antagonist (L-365,260) injection into the caudate nucleus on CCK-8. RESULTS: The radiant heat focused on the tail of rats caused an increase in the evoked discharge of PEN and a reduction in the evoked discharge of PIN. EA stimulation at the bilateral ST 36 acupoints of rats resulted in the inhibition of PEN, the potentiation of PIN, and prolongation of TFL. The analgesic effect of EA was antagonized when CCK-8 was injected into the intracerebral ventricle of rats. The antagonistic effect of CCK-8 on EA analgesia was reversed by injection of CCK-B receptor antagonist (L-365,260) into the caudate nucleus of rats. CONCLUSIONS: Our results suggest that CCK-8 antagonize EA analgesia through its B receptor.

Cholinergic mechanism involved in the nociceptive modulation of dentate gyrus.

Acetylcholine (ACh) causes a wide variety of anti-nociceptive effects. The dentate gyrus (DG) region of the hippocampal formation (HF) has been demonstrated to be involved in nociceptive perception. However, the mechanisms underlying this anti-nociceptive role have not yet been elucidated in the cholinergic pain-related neurons of DG. The electrical activities of pain-related neurons of DG were recorded by a glass microelectrode. Two kinds of pain-related neurons were found: pain-excited neurons (PEN) and pain-inhibited neurons (PIN). The experimental protocol involved intra-DG administration of muscarinic cholinergic receptor (mAChR) agonist or antagonist. Intra-DG microinjection of 1 microl of ACh (0.2 microg/microl) or 1 microl of pilocarpine (0.4 microg/microl) decreased the discharge frequency of PEN and prolonged firing latency, but increased the discharge frequency of PIN and shortened PIN inhibitory duration (ID). Intra-DG administration of 1 microl of atropine (1.0 microg/microl) showed exactly the opposite effects. According to the above experimental results, we can presume that cholinergic pain-related neurons in DG are involved in the modulation of the nociceptive response by affecting the discharge of PEN and PIN.

Morphine dependence changes the role of droperidol on pain-related electric activities in caudate nucleus.

Droperidol causes the blockage of the dopamine receptors in the central nervous system that are involved in pain transmission. However, the mechanism of action of droperidol in pain-related neurons is not clear, and it is still unknown whether opioids are involved in the modulation of this processing. The present study examines the effect of droperidol on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the caudate nucleus (Cd) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. Our results revealed that droperidol decreased the frequency of PEN discharge, and increased the frequency PIN discharge evoked by the noxious stimulation in the Cd of normal rats, while administration of droperidol to morphine-dependent rats produced the opposite response. Those demonstrated that droperidol is involved in the modulation of nociceptive information transmission in Cd, and there were completely opposite responses to painful stimulation between normal and morphine-dependent rats after administration of droperidol.

Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for Modulating Pain-evoked Activities of Neurons in the Hippocampal CA3 Region of Rats.

BACKGROUND: Metabotropic glutamate could contribute to the development of neuropathic pain-related behaviors. Previously, we have confirmed that the glutamic acid and dizocilpine maleate in the hippocampal CA3 region are involved in the modulation of noxious stimulation. However, whether the metabotropic glutamate receptor 7 (mGluR7) can modulate the pain-evoked electrical activities of pain-excited neurons and pain-inhibited neurons in the hippocampal CA3 region is not clear. OBJECTIVE: The study aimed to examine the effects of mGluR7 allosteric agonist N,N'-dibenzhydrylethane- 1,2-diamine dihydrochloride (AMN082) and antagonist 6-(4-methoxyphenyl)-5-methyl-3- pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) on the pain-evoked electrical activities of pain-excited neurons and pain-inhibited neurons in the CA3 region of rats. METHOD: A train of electric impulses applied to the sciatic nerve were used for noxious stimulation. The bio-electrical activities of pain-excited neuron or pain-inhibited neuron in the CA3 region were recorded by a glass microelectrode. RESULTS: Our results exhibited that intra-CA3 region administration of the glutamic acid or AMN082 increased the pain-evoked discharged frequency and shortened the latency of pain-excited neuron, while decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of paininhibited neuron in the CA3 region. The intra-CA3 region microinjection of MMPIP produced the opposite response. CONCLUSION: These findings demonstrated that the glutamic acid and mGluR7 in hippocampal CA3 region are involved in the modulation of nociceptive information transmission by regulating pain-evoked electric activities of pain-excited neurons and pain-inhibited neurons.

[Influence of glutamate and NMDA-receptor antagonist MK-801 on the electric activities of pain-excitation neurons in the nucleus accumbens of rats].

The experiment explored the influence of glutamic acid (Glu) and the NMDA-receptor antagonist dizocilpine maleate (MK-801) on the pain-evoked responses of pain-excitation neurons (PEN) in the nucleus accumbens (NAc) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN in NAc were recorded by glass microelectrode. We observed the influence of intracerebroventricular (icv) injection of Glu and microinjection of MK-801 into the NAc on the noxious stimulation-evoked activities of PEN in NAc. The results showed that the noxious stimulation potentiated the electric activities of PEN in NAc. Intracerebroventricular injection of Glu (10 nmol/10 microl) increased the frequency of the discharge of PEN evoked by the noxious stimulation in NAc, the Glu-induced response was blocked by the injection of MK-801 (1.0 nmol/0.5 microl) into NAc. MK-801 partly inhibited the response of PEN upon the noxious stimulation. It is therefore suggested that the facilitatory effect of Glu on PEN response in NAc to the noxious stimulation is mediated by NMDA receptors, and that Glu and NMDA receptors are involved in the modulation of nociceptive information transmission in the NAc.

The involvement of norepinephrine in pain modulation in the nucleus accumbens of morphine-dependent rats.

Opioids are effective analgesics used clinically for both acute and chronic pain management. However, repeated opioid treatment can induce serious side effects such as nausea, vomiting, drowsiness, respiratory depression, euphoria, dependence, hyperalgesia, and tolerance. The mechanism of noxious information transmission in the central nervous system following dependence is still not clear. Norepinephrine (NE), an important neurotransmitter, participates both in the process of opioid dependence and also pain modulation in the central nervous system. In this study, we examined the role of NE on the evoked discharges of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the nucleus accumbens (NAc) of rats, following the development of morphine dependence. Our results revealed that NE inhibited the evoked discharges of PENs and attenuated the inhibition of PINs, while phentolamine enhanced the evoked discharges of PENs and facilitated the inhibition of PINs. These results indicate that the inhibitory action of NE on pain modulation acts via alpha adrenoceptors in the NAc of morphine-dependent rats.

Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

Acetylcholine plays an antinociceptive role by modulating pain-induced discharges of pain-related neurons in the caudate putamen of rats.

The caudate putamen (CPu) has been suggested to be involved in nociceptive modulation. Some neurotransmitters, including acetylcholine (ACh), participate in pain modulation in the central nervous system. However, the active mechanism of ACh on the pain-related neurons in the CPu remains unclear. This study aimed to investigate the effects of the cholinergic agonists ACh and pilocarpine and the muscarinic ACh receptor antagonist atropine on the pain-induced response of pain-related neurons in the CPu of Wistar rats. Trains of electrical impulses applied to the sciatic nerve of rat were used as the noxious stimulus. The electrical activities of pain-excited neurons (PENs) or pain-inhibited neurons (PINs) in the CPu were recorded by a glass microelectrode. Our results showed that an intra-CPu injection of 4 µg/2 µl ACh or pilocarpine decreased and increased the pain-induced discharge frequency in the PENs and PINs, respectively. Intra-CPu administration of 1 µg/2 µl atropine produced the opposite effect on these neurons. These findings indicate that ACh may play an analgesic role by affecting the electric activities of PENs and PINs, and the muscarinic pathway may be involved in the modulation of pain perception in the CPu.

Modulatory role of glutamic acid on the electrical activities of pain-related neurons in the hippocampal CA3 region.

Glutamic acid (Glu) participates in pain modulation of the central nervous system. The CA3 region of the hippocampal formation has been suggested to be involved in nociceptive perception. However, it is unknown whether Glu could modulate the electrical activities of pain-related neurons in the hippocampal CA3 region. The present study aimed to determine the effects of Glu and its receptor antagonist MK-801 in the pain-evoked response of both pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of normal rats. We used a train of electric impulses applied to the sciatic nerve as noxious stimulation. The electrical activities of either PENs or PINs in the hippocampal CA3 region were recorded by a glass microelectrode. The results revealed that intra-CA3 region microinjection of Glu (0.5 µg/1 µl) increased the evoked firing frequency and shortened the firing latency of PEN, while decreased the evoked firing frequency and prolonged the inhibitory duration of PIN in the hippocampal CA3 region of rat evoked by the noxious stimulation. Intra-CA3 region administration of MK-801 (0.25 µg/1 µl) produced the opposite response. These results suggest that Glu and its receptors in hippocampal CA3 region are involved in the modulation of nociceptive information transmission by affecting the electric activities of PENs and PINs.

Effects of norepinephrine on the electrical activities of pain-related neurons in the rat nucleus accumbens.

This study examined the effects of norepinephrine (NE) and phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the nucleus accumbens (NAc) of Wistar rats. Trains of electric pulses applied to the right sciatic nerve were used to provide noxious stimulation, and the discharges of PENs and PINs were recorded using a glass microelectrode. Our results revealed that in response to noxious stimulation, NE decreases the evoked discharge frequency of PENs and increases the evoked discharge frequency of PINs in the NAc of healthy rats, whereas phentolamine produced opposite responses. These results demonstrate that NE is involved in the modulation of nociceptive information transmission in the NAc.

Microinjection of different doses of norepinephrine into the caudate putamen produces opposing effects in rats.

It has been proven that norepinephrine (NE) regulates antinociception through its action on alpha-adrenoceptors located in brain nuclei, spinal cord, and peripheral organs. However, the supraspinal mechanism of noradrenergic pain modulation is controversial. The present study was aimed at investigating the nociceptive effects induced by injecting different doses of NE and phentolamine into the caudate putamen (CPU) of rats. The thermal pain threshold of the rats was measured by performing a tail-flick test. The tail-flick latency (TFL) was measured at 2-60 min after microinjection of the drugs. Our results revealed that the thermal pain threshold increased (long TFL) after the administration of a low dose of NE (2 microg/2 microl) and decreased (short TFL) after injection of a high dose of NE (8 microg/2 microl). In contrast, the pain threshold decreased after the administration of a low dose of phentolamine (1 microg/2 microl), while it increased after injection of a high dose of phentolamine (4 microg/2 microl). These results indicated that the injection of different doses of NE in the CPU of the rats produced opposite effects on the pain threshold, as determined by the tail-flick tests.

Noradrenergic mechanism involved in the nociceptive modulation of nociceptive-related neurons in the caudate putamen.

Norepinephrine (NE) participates in pain modulation of the central nervous system. The caudate putamen (CPu) is one region of the basal ganglia that has been demonstrated to be involved in nociceptive perception. Our previous work has shown that microinjection of different doses of norepinephrine into the CPu produces opposing effects in the tail-flick latency (TFL) of rats. However, the mechanism of action of NE on the pain-related neurons in the CPu remains unclear. The present study examined the effects of NE and the alpha-adrenoceptor antagonist phentolamine on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the CPu of rats. Trains of electric impulses were used for noxious stimulation, and were applied to the sciatic nerve. The electrical activities of pain-related neurons in the CPu were recorded by a glass microelectrode. The results revealed that intra-CPu microinjection of NE (8microg/2microl) increased evoked firing frequency of PEN and shortened the firing latency, but decreased the evoked firing frequency of PIN and prolonged the inhibitory duration (ID). Intra-CPu administration of phentolamine (4microg/2microl) showed the opposite effects. The above results suggest that NE in the CPu modulates nociception by affecting the baseline firing rates of PENs and PINs.

Modulation of gamma-aminobutyric acid on painful sense in central nervous system of morphine-dependent rats.

OBJECTIVE: To observe the effects of gamma-aminobutyric acid (GABA) on the electric activities of pain-excited neurons (PEN) in nucleus accumbens (NAc) in central nervous system (CNS) of morphine-dependent rats. METHODS: After GABA or the GABA(A)-receptor antagonist, bicuculline (Bic), was injected into cerebral ventricles or NAc, right sciatic nerve was stimulated by electrical pulses, which was considered as traumatic pain stimulation. Extracellular recordings methods were used to record the electric activities of PEN in NAc. RESULTS: When GABA was injected into intracerebroventricle (ICV) as well as NAc, it could decrease the pain-evoked discharge frequency and prolong the latency of PEN. Bic could interdict the above effects of GABA on the electric activities of PEN. CONCLUSION: Exogenous GABA might have an inhibitory effect on the central pain adjustment. Furthermore, GABA and GABA(A) receptor participate and mediate the traumatic information transmission process in CNS.

[Phentolamine antagonizes the effects of norepinephrine on the activity of pain-related neurons in the parafascicular nucleus of morphine-dependent rats].

OBJECTIVE: To examine the antagonization of phentolamine against the effects of norepinephrine (NE) on the activity of pain-related neurons in the parafascicular nucleus of morphine-dependent rats. METHODS: Electric impulses were applied as nociceptive stimulus to the right sciatic nerve of morphine-dependent rats, and the discharges of the pain-related neurons in the parafascicular nucleus were recorded by extracellular recording method with glass microelectrodes. RESULTS: Intracerebroventricular injection of norepinephrine resulted in the inhibition of evoked response of the pain-excited neurons as well as the excitation of evoked response of the pain-inhibiting neurons. Both the inhibitory effect on the electric discharges of the pain-excited neurons and the excitatory effect on the pain-inhibiting neurons of norepinephrine were almost completely blocked by intracerebroventricular administration of phentolamine. CONCLUSION: Phentolamine antagonizes the inhibitory effect of norepinephrine on the activity of pain-related neurons in the parafascicular nucleus in morphine-dependent rats, and norepinephrine may play an important role in the integration of the pain signal through the alpha-receptors.

Differential effects of dopamine on pain-related electric activities in normal rats and morphinistic rats.

OBJECTIVE: To investigate the influence of dopamine (DA) and DA receptor's antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. METHODS: The influence of DA on the electric activity of the pain-excited neuron (PEN) in the caudate nucleus (Cd) of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. RESULTS: DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. CONCLUSION: The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.

Effect of acetylcholine on pain-related electric activities in hippocampal CA1 area of normal and morphinistic rats.

OBJECTIVE: To examine the effect of acetylcholine (ACh) on the electric activities of pain-excitation neurons (PEN) and pain-inhibitation neurons (PIN) in the hippocampal CA1 area of normal rats or morphinistic rats, and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction. METHODS: The trains of electric impulses applied to sciatic nerve were set as noxious stimulation. The discharges of PEN and PIN in the CA1 area were recorded extracellularly by glass microelectrode. We observed the influence of intracerebroventricular (i.c.v.) injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area. RESULTS: Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats. In normal rats, ACh decrease the pain-evoked discharge frequency of PEN, while increased the frequency of PIN. These effects reached the peak value at 4 min after injection of ACh. In morphinistic rats, ACh also inhibited the PEN electric activity and potentialized the PIN electric activity, but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine. CONCLUSION: Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation. Morphine addiction attenuated the sensitivity of pain-related neurons to the noxious information.

[The relation between amygdaloid nucleus in rats and pain modulation].

AIM: To research the influence of noxious stimuli on the electric activities of pain-related neurons in several subnuclei of Amygdaloid Nucleus in rats. METHODS: Trains of the electric impulses applied to the sciatic nerve were used as noxious stimuli. The discharges of neurons were channeled off by glass microelectrode. RESULTS: Pain-related neurons existed in several subnuclei of Amygdaloid Nucleus. When the noxious stimuli were administered the frequency of discharges of pain-excited neurons (PEN) was increased while the frequency of pain-inhibited neurons (PIN) was decreased to the lowest level. The electric activities of PEN and PIN were matched with each other. Intraperitoneal injection of morphine (10 mg/kg) antagonized the effects of noxious stimuli on the pain-related neurons. CONCLUSION: Several subnuclei of Amygdaloid Nucleus play an essential role in perceiving, integrating and transmitting the pain impulses. They are a part of the central nervous system in which pain information is controlled and managed.