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Activating primary afferent TRPV1-positive (TRPV1

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA(A) receptor (GABA(A)R) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Post-traumatic stress disorder (PTSD) has become epidemic following severely stressful incidents. Previous studies have shown that brain-derived neurotrophic factor (BDNF) has anxiolytic effects on various anxiety or depression disorders including PTSD. However, the detailed mechanisms of BDNF for treating PTSD were rarely investigated. In the current study, single-prolonged stress (SPS) was used as an animal model recapitulating specific aspects for a PTSD-like phenotype. The effects of BDNF on SPS-induced anxiety-like behaviors were investigated. We showed that the levels of BDNF in the cerebro-spinal fluid (CSF) were significantly reduced after the rats experienced SPS. The SPS-induced reductions of percentages of time spent in the central area to total time in the open field test, were dose-dependently mitigated after BDNF intracerebroventricular (i.c.v.) injections. BDNF i.c.v. administration also dose-dependently increased the preference of the light box in the light-dark box test. Both expressions of tyrosine kinase receptor B (TrkB) protein and mRNA in the prefrontal cortex (PFC) and amygdala were significantly increased after SPS challenges. BDNF i.c.v. administration attenuated these compensatory increases of TrkB. At last, the anxiolytic effects of BDNF on SPS model were also observed by using other two injection methods. These results inspired us to study that different administrations of BDNF were used in patients with PTSD in the future, in-depthly.

Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.

As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENTStudies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+pathway in a descending facilitatory mechanism underlying neuropathic pain.

Background/Aims: Spinal dorsal horn (SDH) is one of the most important regions for analgesia produced by endomorphin-2 (EM2), which has a higher affinity and specificity for the µ-opioid receptor (MOR) than morphine. Many studies have focused on substantia gelatinosa (SG, lamina II) neurons to elucidate the cellular basis for its antinociceptive effects. However, the complicated types and local circuits of interneurons in the SG make it difficult to understand the real effects of EM2. Therefore, in the present study, we examined the effects of EM2 on projection neurons (PNs) in lamina I. Methods: Tracing, immunofluoresence, and immunoelectron methods were used to examine the morphological connections between EM2-immunoreactive (-ir) terminals and PNs. By using in vitro whole cell patch clamp recording technique, we investigated the functional effects of EM2 on PNs. Results: EM2-ir afferent terminals directly contacted PNs projecting to the parabrachial nucleus in lamina I. Their synaptic connections were further confirmed by immunoelectron microscopy, most of which were asymmetric synapses. It was found that EM2 had a strong inhibitory effect on the frequency, but not amplitude, of the spontaneous excitatory postsynaptic current (sEPSC) of the spinoparabrachial PNs in lamina I, which could be reversed by MOR antagonist CTOP. However, their spontaneous inhibitory postsynaptic current (sIPSC) and intrinsic properties were not changed after EM2 application. Conclusion: Applying EM2 to the SDH could produce analgesia through inhibiting the activities of the spinoparabrachial PNs in lamina I by reducing presynaptic neurotransmitters release from the primary afferent terminals.

5-hydroxytryptamine (5-HT) transmission in the medial prefrontal cortex (mPFC) enhances or suppresses signal outflow to influence emotion-/cognition-based function performances and, putatively, the autonomic responses. The top-down cortical modulation of autonomic activities may be mediated in part through projections from mPFC to brain stem dorsal vagal complex (DVC). The abundant and heterogeneous densities of 5-HT fibers across laminae in mPFC suggest serotonergic innervation of mPFC-DVC projection neurons whereby endogenous 5-HT acts to regulate autonomic activities. The present study investigated the physical relationship between 5-HT fibers and the autonomic-related mPFC neurons by examining and quantitatively characterizing the 5-HT contacts upon retrogradely labeled mPFC-DVC projection neurons in pre- and infra-limbic cortices (PrL/IL) with light and electron microscopies combined with immunocytochemistry for 5-HT and presynaptic vesicle marker synaptophysin (Syn). 5-HT varicosities were observed, under confocal microscope, to form close appositions to or, at ultrastructural level, to form asymmetric axodendritic synapses and direct contacts upon the target neurons. About 16% of the entire 5-HTergic varicosities in lamina V of PrL/IL coexpressed Syn and about 24% of the peri-somatic 5-HTergic swellings demonstrated Syn-immunoreactivity (ir), suggesting a low frequency of putative synapses estimated at optical level. Ultrastructurally, examination of thirty-seven serially cut thin 5-HT boutons closely apposed to the labeled dendritic profiles demonstrated that only three contacts presented with identifiable asymmetric, synaptic membrane specializations. These data provide the first and direct morphological evidence supporting that endogenous 5-HT may be released mainly via direct contacts bearing no identifiable synaptic specializations as well as synapses, targeting autonomic-related mPFC neurons for autonomic regulation.

The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are strongly implicated in the sensory-discriminative and affective/emotional aspects of orofacial pain, respectively. These T-T and T-P projection fibers originate from the spinal trigeminal nucleus (Vsp). We previously determined that many vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were distributed in the Vsp of the adult rat, and most of these neurons sent their axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA-positive projection neurons exist that send their axons to both the thalamus and the parabrachial nucleus (PBN) has not been reported. Thus, in the present study, dual retrograde tract tracing was used in combination with fluorescence in situ hybridization (FISH) for VGLUT1 or VGLUT2 mRNA to identify the existence of VGLUT1 or VGLUT2 mRNA neurons that send collateral projections to both the thalamus and the PBN. Neurons in the Vsp that send collateral projections to both the thalamus and the PBN were mainly VGLUT2 mRNA-positive, with a proportion of 90.3%, 93.0% and 85.4% in the oral (Vo), interpolar (Vi) and caudal (Vc) subnucleus of the Vsp, respectively. Moreover, approximately 34.0% of the collateral projection neurons in the Vc showed Fos immunopositivity after injection of formalin into the lip, and parts of calcitonin gene-related peptide (CGRP)-immunopositive axonal varicosities were in direct contact with the Vc collateral projection neurons. These results indicate that most collateral projection neurons in the Vsp, particularly in the Vc, which express mainly VGLUT2, may relay orofacial nociceptive information directly to the thalamus and PBN via axon collaterals.

Aims The present study aims to test whether astrocytes contribute to glucocorticoid-mediated diabetic mechanical allodynia. Methods Streptozotocin (STZ)-induced diabetic rats were used in our study. The intrathecal operation was performed 21 days after the onset of diabetes. Diabetic mechanical allodynia was present 28 d after the onset of diabetes, and the mechanical threshold was tested using von Frey filaments. Immunohistochemistry, including immunofluorescent histochemical staining, was performed to observe the morphology of the spinal dorsal horn (SDH). Western blot analysis was employed as a semi-quantitative assay of the expression levels of GFAP and NDRG2 associated with diabetic mechanical allodynia. Results Diabetic rats displayed mechanical allodynia and activated astrocytes in the SDH 28 days after the onset of diabetes. This allodynia was attenuated by intrathecal administration of the astrocyte-specific inhibitor l -α-aminoadipate. In parallel, intrathecal injection of RU486, a glucocorticoid receptor antagonist, inhibited the activation of astrocytes in the SDH, alleviating the diabetes-induced mechanical allodynia. Furthermore, we found that dorsal horn astrocytes express abundant N-myc downstream-regulated gene 2 (NDRG2), which contributes to astrocyte reactivity. NDRG2 was over-expressed in activated astrocytes in diabetic rats with mechanical allodynia. Intrathecal injection of RU486 prevented the over-expression of NDRG2, which reversed the astrocyte reactivity and diabetic tactile allodynia. Conclusions These results suggest that glucocorticoid-mediated over-expression of NDRG2 may contribute to the activation of dorsal horn astrocytes, which play a crucial role in diabetic mechanical allodynia. Thus, inhibiting glucocorticoid receptors and/or astrocyte reactivity in the SDH may be a therapeutic strategy for treating diabetic tactile allodynia.

Motor impairment is one of the serious side-effects of morphine, which is an exogenous agonist of the μ opioid receptor (MOR) as well as a widely-used analgesic drug in clinical practice for chronic pain treatment. Endomorphins (EMs, including EM-1 and EM-2), the most effective and specific endogenous agonists of the MOR, exert more potent analgesia in acute and neuropathic pain than other opiates, such as morphine. Although EMs had fewer side-effects comparing to other opiates, motor impairment was still one unwanted reaction which limited its clinical application. In order to prevent and treat the motor impairment, it is critical to reveal the neural mechanisms underlying such locomotion disorder. The purpose of the present study was to reveal the neural mechanisms underlying the effects of endomorphin-2 (EM-2) on the activity of motoneurons in the spinal ventral horn. First, we examine the distribution of EM-2-immunoreactive (IR) primary afferent fibers and their synaptic connections with the motoneurons innervating the skeletal muscles of the lower limb revealed by sciatic nerve retrograde tracing. The results showed that EM-2-IR fibers and terminals were sparsely observed in lamina IX and they formed symmetric synaptic connections with the motoneurons within lamina IX of the spinal ventral horn. Then, whole-cell patch-clamp technique was used to observe the effects of EM-2 on the spontaneous excitatory postsynaptic current (sEPSC) of motoneurons in lamina IX. The results showed that EM-2 could decrease both the frequency and amplitude of the sEPSC of the motoneurons in lamina IX, which was reversed by the MOR antagonist CTOP. These results indicate that EM-2-IR fibers originated from primary afferent fibers form symmetric synaptic connections with motoneurons innervating skeletal muscles of the lower limbs in lamina IX of the spinal ventral horn and EM-2 might exert inhibitory effects on the activities of these motoneurons through both presynaptic and postsynaptic mechanisms.

Aims To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. Main methods We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20 mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Key findings Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA + poly(lactic-co-glycolic acid) (PLGA) + stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Significance Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response.

Stressful stimuli can exacerbate persistent pain disorder. However, the underlying mechanism is still unknown. Here, to reveal the underlying mechanism for stressful stimuli-induced hyperalgesia in chronic pain, we investigated the effect of extracellular signal-regulated kinase1/2 (ERK1/2) activation on pain hypersensitivity using single-prolonged stress (SPS) model, complete Freund's adjuvant (CFA) model and SPS + CFA model. The experimental results revealed significantly reduced paw withdrawal threshold in the SPS, CFA, and SPS + CFA group compared with the control group. However, the increased phosphorylation of ERK1/2 in the medial prefrontal cortex (mPFC) was observed in the SPS- or SPS + CFA-exposed group but not the CFA group compared with control group. There was also a significant increase in mPFC ERK1/2 phosphorylation and mechanical allodynia after SPS + CFA treatment compared to SPS or CFA treatment alone. Furthermore, inhibiting ERK1/2 phosphorylation by microinjection of U0126, a MAPK kinase (MEK) inhibitor, into the mPFC attenuated SPS + CFA- and SPS- but not CFA-induced mechanical allodynia, anxiety-like behavior, and cognitive impairments. These results suggest that the activation of ERK1/2 in the mPFC may contribute to the process of stress-induced cognitive and emotional disorders, leading to an increase in pain sensitivity.

The lateral capsular division of central nucleus of amygdala (CeC) contains neurons using γ-amino butyric acid (GABA) as the predominant neurotransmitter and expresses abundant calcitonin gene-related peptide (CGRP)-positive terminals. However, the relationship between them has not been revealed yet. Using GAD67-green fluorescent protein (GFP) knock-in mouse, we investigated the neurochemical features of synapses between CGRP-positive terminals and GABAergic neurons within CeC and the potential involvement of CGRP1 receptor by combining fluorescent in situ hybridization for CGRP1 receptor mRNA with immunofluorescent histochemistry for GFP and CGRP. The ultrastructures of these synapses were investigated with pre-embedding electron microscopy for GFP and CGRP. We found that some GABAergic neurons in the CeC received parabrachial nucleus (PBN) derived CGRP innervations and some of these GABAergic neurons can be activated by subcutaneous injection of formalin. Moreover, more than 90 % GABAergic neurons innervated by CGRP-positive terminal also express CGRP1 receptor mRNA. The CGRP-positive fibers made symmetric synapses onto the GABAergic somata, and asymmetric synapses onto the GABA-LI dendritic shafts and spines. This study provides direct ultrastructural evidences for the synaptic contacts between CGRP-positive terminals and GABAergic neurons within the CeC, which may underlie the pain-related neural pathway from PBN to CeC and be involved in the chronic pain modulation.

In order to reduce the iterative decoding delay of convolutional turbo codes, this paper presents a concurrent decoding algorithm for the hardware implementation of turbo convolutional decoders. Different than a general turbo code, the hardware turbo decoder based on the proposed algorithm can update the priori information of message for each component code in a bit-by-bit manner as soon as it is generated by the other component code. The two component codes in a turbo code can thus be decoded concurrently, by using a single MAP decoder, subsequently reducing the decoding latency by approximately half while maintaining the bit error rate performance and a comparable hardware complexity, as a general turbo decoder.

Introduction We employed a nanosilver-collagen scaffold and tested its effects on inhibiting bacteria and facilitating nerve regeneration. Methods Based on our previous research, we prepared bionic scaffolds with different concentrations of nanosilver and examined their internal structures by scanning electron microscopy and energy dispersive spectroscopy. We implanted these scaffolds or autologous nerve grafts into rats to repair a 10-mm injury of the sciatic nerve. Results The 2 mg/ml group showed a >10 mm bacterial inhibition zone in all 3 types of bacterial culture dishes. At day 60 postsurgery, the 2 mg/ml group also showed the highest amplitude of evoked potential (AMP) and nerve conduction velocity (NCV). The regenerating nerves in the 2 mg/ml group were denser and more mature, and with thicker and well-arrayed myelin sheath. Conclusions These results demonstrate that nanosilver scaffolds (2 mg/ml group) were effective in inhibiting bacteria both in vitro and in vivo, and reduced the contamination-caused immune responses, which in turn promoted nerve regeneration and functional recovery.

Opiates are commonly used analgesics that often cause clinical respiratory depression. However, their underlying mechanisms remain unclear. Endomorphin-2 (EM2) is a novel, endogenous tetrapeptide opioid with very high affinity and selectivity for the μ-opioid receptor (MOR). The pre-Botzinger complex (pre-BotC) is considered the center of respiratory rhythm generation, and the synaptic connections in this region are essential for respiratory rhythm. The present study identified EM2-like immunoreactive (LI) axonal terminals in the pre-BotC of adult rats. Some EM2-LI axonal terminals made principally symmetric synapses with neurokinin 1 receptor (NK1R)-LI or MOR-LI neuronal dendritic processes in the pre-BotC. Unilateral microinjection of EM2 into the pre-BotC decreased breathing frequency and amplitude. A prior microinjection of the selective MOR antagonist β-funaltrexamine (β-FNA) into the pre-BotC prevented the effects of EM2. The present results suggest that EM2-LI axonal terminals modulate NK1R-expressing neurons in the pre-BotC and that EM2 plays a role in respiratory depression through MORs in the pre-BotC.

This paper presents ringed bit-parallel systolic multipliers for computing AB+C over a class of finite fields GF(2^m), in which all elements are represented using a root of an all-one polynomial or an equally spaced polynomial. Compared to other related multipliers, the proposed multipliers reveal properties of lower hardware complexity, lower latency and free of global connection. Furthermore, we proposed a general rule to plan the multipliers. This rule makes the planning easy.

The periaqueductal gray (PAG) modulates nociception via a descending pathway that relays in the rostral ventromedial medulla (RVM) and terminates in the spinal cord. Previous behavioral pharmacology and electrophysiological evidence suggests that brain-derived neurotrophic factor (BDNF) plays an important role in descending pain modulation, likely through the PAG-RVM pathway. However, there still lacks detailed information on the distribution of BDNF, activation of BDNF-containing neurons projecting to RVM in the condition of pain, and neurochemical properties of these neurons within the PAG. Through fluorescent in situ hybridization (FISH) and immunofluorescent staining, the homogenous distributions of BDNF mRNA and protein were observed in the four subregions of PAG. Both neurons and astrocytes expressed BDNF, but not microglias. By combining retrograde tracing methods and formalin pain model, there were more BDNF-containing neurons projecting to RVM being activated in the ventrolateral PAG (vlPAG) than other subregions of PAG. The neurochemical properties of BDNF-containing projection neurons in the vlPAG were investigated. BDNF-containing projection neurons expressed auto receptor Tropomyosin-related kinase B (TrkB) in addition to serotonin (5-HT), neurotensin (NT), substance P (SP), calcitonin gene related peptide (CGRP), nitric oxide synthase (NOS), and parvalbumin (PV) but not tyrosine decarboxylase (TH). It is speculated that BDNF released from projection neurons in the vlPAG might participate in the descending pain modulation through enhancing the presynaptic release of other neuroactive substances (NSs) in the RVM.

Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the μ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III.

Aims To investigate the effect of locally slow-released rapamycin (RAPA) from the bionic peripheral nerve scaffold on rat sciatic nerve regeneration in the early phase of nerve injury. Main methods Slow-releasing RAPA-polyhydroxy alcohol (PLGA) microspheres were prepared and tested for microsphere diameter and slow-release effect in vitro after loading onto nerve scaffold. A total of 48 male SD rats were randomly divided into control group and 3 experimental groups as follows: group 1: RAPA-PLGA scaffold; group 2: RAPA scaffold; and group 3: scaffold alone. In the control group, a 15 mm sciatic nerve was excised and religated reversely. In the experimental groups, the scaffolds were used to bridge a defect of 15 mm sciatic nerve. The outcome of nerve regeneration was evaluated using neurophysiological and neuromuscular morphological techniques. Key findings The RAPA-PLGA microspheres displayed a smooth exterior. The slow-release of RAPA in group 1 lasted for 14 days. The sciatic nerve function index (SFI) and electrophysiological and morphological features were examined 12 weeks after the surgery in all groups to reveal various degrees of ipsilateral sciatic nerve regeneration. The SFI values at 12 weeks showed no significant difference between the RAPA-PLGA scaffold and control groups; morphological observations revealed that the outcomes of nerve regeneration in the above 2 groups were similar and significantly better than those in the RAPA scaffold and scaffold alone groups. Significance RAPA-PLGA microsphere-loaded bionic peripheral nerve scaffold gradually released RAPA locally in the early phase of sciatic nerve regeneration, reduced the secondary nerve injury, and evidently promoted the regeneration of peripheral nerve.

Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect in pain modulation. To investigate the potential interactions of EM2- and substance P (SP)-containing primary afferents and γ-amino butyric acid (GABA)-containing interneurons in lamina II in nociceptive transmission, connections between EM2- and SP-containing terminals and GABAergic neurons in the spinal dorsal horn were studied. Double-immunofluorescent labeling showed that approximately 62.3 % of EM2-immunoreactive neurons exhibited SP-immunostaining, and 76.9 % of SP-immunoreactive neurons demonstrated EM2-immunoreactivities in the dorsal root ganglion (DRG). Dense double-labeled EM2- and SP-immunoreactivities were mainly observed in lamina II of the lumbar dorsal horn. Furthermore, triple-immunofluorescent labeling results revealed that EM2 and SP double-labeled terminals overlapped with GABAergic neurons. Immuno-electron microscopy confirmed that the EM2- or SP-immunoreactive terminals formed synapses with GABA-immunoreactive dendrites in lamina II of the lumbar dorsal horn. During noxious information transmission induced by formalin plantar injection, GABAergic neurons expressing FOS in their nuclei were contacted with EM2- or SP-immunoreactive terminals. These results suggest that the interactions between EM2- and SP-containing terminals and GABAergic interneurons in the lamina II influence pain transmission and modulation in the spinal dorsal horn.

The urinary bladder is innervated by parasympathetic preganglionic neurons (PPNs) that express μ-opioid receptors (MOR) in the sacral parasympathetic nucleus (SPN) at lumbosacral segments L6-S1. The SPN also contains endomorphin 2 (EM2)-immunoreactive (IR) fibers and terminals. EM2 is the endogenous ligand of MOR. In the present study, retrograde tract-tracing with cholera toxin subunit b (CTb) or wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) via the pelvic nerve combined with immunohistochemical staining for EM2 and MOR to identify PPNs within the SPN as well as synaptic connections between the EM2-IR terminals and MOR-expressing PPNs in the SPN of the rat. After CTb was injected into the pelvic nerve, CTb retrogradely labeled neurons were almost exclusively located in the lateral part of the intermediolateral gray matter at L6-S1 of the lumbosacral spinal cord. All of the them also expressed MOR. EM2-IR terminals formed symmetric synapses with MOR-IR, WGA-HRP-labeled and WGA-HRP/MOR double-labeled neuronal cell bodies and dendrites within the SPN. These results provided morphological evidence that EM2-containing axon terminals formed symmetric synapses with MOR-expressing PPNs in the SPN. The present results also show that EM2 and MOR might be involved in both the homeostatic control and information transmission of micturition.

The vesicular glutamate transporters, VGLUT1 and VGLUT2, reportedly display complementary distribution in the rat brain. However, co-expression of them in single neurons has been reported in some brain areas. We previously found co-expression of VGLUT1 and VGLUT2 mRNAs in a number of single neurons in the principal sensory trigeminal nucleus (Vp) of the adult rat; the majority of these neurons sent their axons to the thalamic regions around the posteromedial ventral nucleus (VPM) and the posterior nuclei (Po). It is well known that trigeminothalamic (T-T) projection fibers arise not only from the Vp but also from the spinal trigeminal nucleus (Vsp), and that trigeminocerebellar (T-C) projection fibers take their origins from both of the Vp and Vsp. Thus, in the present study, we examined the expression of VGLUT1 and VGLUT2 in Vp and Vsp neurons that sent their axons to the VPM/Po regions or the cortical regions of the cerebellum. For this purpose, we combined fluorescence in situ hybridization (FISH) histochemistry with retrograde tract-tracing; immunofluorescence histochemistry was also combined with anterograde tract-tracing. The results indicate that glutamatergic Vsp neurons sending their axons to the cerebellar cortical regions mainly express VGLUT1, whereas glutamatergic Vsp neurons sending their axons to the thalamic regions express VGLUT2. The present data, in combination with those of our previous study, indicate that glutamatergic Vp neurons projecting to the cerebellar cortical regions express mainly VGLUT1, whereas the majority of glutamatergic Vp neurons projecting to the thalamus co-express VGLUT1 and VGLUT2.

The brainstem premotor neurons of the facial nucleus (VII) and hypoglossal (XII) nucleus can integrate orofacial nociceptive input from the caudal spinal trigeminal nucleus (Vc) and coordinate orofacial nociceptive reflex (ONR) responses. However, the synaptoarchitectures of the ONR pathways are still unknown. In the current study, we examined the distribution of GABAergic premotor neurons in the brainstem local ONR pathways, their connections with the Vc projections joining the brainstem ONR pathways and the neurochemical properties of these connections. Retrograde tracer fluoro-gold (FG) was injected into the VII or XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the Vc. Immunofluorescence histochemical labeling for inhibitory/excitatory neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor neurons were mainly distributed bilaterally in the ponto-medullary reticular formation with an ipsilateral dominance. Some GABAergic premotor neurons made close appositions to the BDA-labeled fibers coming from the Vc, and these appostions were mainly distributed in the parvicellular reticular formation (PCRt), dorsal medullary reticular formation (MdD), and supratrigeminal nucleus (Vsup). We further examined the synaptic relationships between the Vc projecting fibers and premotor neurons in the VII or XII under the confocal laser-scanning microscope and electron microscope, and found that the BDA-labeled axonal terminals that made asymmetric synapses on premotor neurons showed vesicular glutamate transporter 2 (VGluT2) like immunoreactivity. These results indicate that the GABAergic premotor neurons receive excitatory neurotransmission from the Vc and may contribute to modulating the generation of the tonic ONR.

Recently, there has been intensive focus on turbo codes which have low decoding latency. To reduce the iterative delay resulted from (de)interleaver; a new parallel algorithm for turbo decoder is proposed. Different than the previous approaches which use multiple units to process sub-block MAP decoding in parallel, the new parallel turbo decoder immediately passes the extrinsic information of one component decoder to the other decoders bit-by-bit. The decoding processes of component decoders perform concurrently and the (de)interleaver delay is eliminated. Simulation results demonstrate that with this parallel scheme, decoding latency is reduced while the performance in terms of BER is comparable, and in some cases superior, to a general turbo decoder. Furthermore, the proposed parallel algorithm can be used to cooperate with those parallel MAP decoding schemes to reduce more decoding latency.

To improve the performance of hybrid concatenated convolutional codes (HCCC); a modified Log-MAP algorithm and an enhanced HCCC are introduced and demonstrated to be efficient and practical by simulation results. The new coding scheme achieves about 1.0 dB additional coding gain, compared to the general turbo coding scheme at a BER = 10-6, with a frame length of 8192-bit. The system complexity and decoding latency of the new scheme is lower than the HCCC proposed by Divsalar and Pollara (1997) within acceptable performance degradation. Since the bit error-rate of the proposed HCCC can be dramatically reduced by slightly increasing signal-to-noise ratio, the new hybrid concatenated coding scheme is very suitable for those communication environments in which high reliability is important.

To reduce the iterative decoding time in turbo coding, a new parallel decoding algorithm for turbo decoders is proposed. Different than the previous approaches of using multiple SISO decoders to process sub-block MAP decoding in parallel, the new parallel turbo decoder immediately passes the extrinsic information of each message bit which is generated by one SISO decoder to the other SISO decoders bit by bit. Thus, the component decoders corresponding to different received sequence perform in parallel and the interleaver delay is eliminated. Simulation results show that with this parallel scheme, decoding time is halved while the performance in terms of BER is comparable, and in some cases superior, to the general turbo decoder.

This paper offers a new bit-parallel systolic multiplier for GF(2/sup m/) using the weakly dual basis. The multiplier is composed of two units $multiplication and transformation. The structure of the multiplication unit includes m/sup 2/ cells, each cell is composed of one 2-input AND gate, one 2-input XOR gate and three/four 1-bit latches. The structure of the transformation unit is established by the 2-input XOR-tree. The latency of the multiplier only requires m+[log/sub 2/m] clock cycles.