Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

BACKGROUND: Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown. METHODS: The partial infraorbital nerve transection (pIONT) was used to induce trigeminal neuropathic pain in mice. The expression of Ccl7, Ccr1, Ccr2, and Ccr3 was examined by real-time quantitative polymerase chain reaction. The distribution of CCL7, CCR2, and CCR3 was detected by immunofluorescence double-staining. The activation of extracellular signal-regulated kinase (ERK) was examined by Western blot and immunofluorescence. The effect of CCL7 on neuronal excitability was tested by whole-cell patch clamp recording. The effect of selective antagonists for CCR1, CCR2, and CCR3 on pain hypersensitivity was checked by behavioral testing. RESULTS: Ccl7 was persistently increased in neurons of TG after pIONT, and specific inhibition of CCL7 in the TG effectively relieved pIONT-induced orofacial mechanical allodynia. Intra-TG injection of recombinant CCL7 induced mechanical allodynia and increased the phosphorylation of ERK in the TG. Incubation of CCL7 with TG neurons also dose-dependently enhanced the neuronal excitability. Furthermore, pIONT increased the expression of CCL7 receptors Ccr1, Ccr2, and Ccr3. The intra-TG injection of the specific antagonist of CCR2 or CCR3 but not of CCR1 alleviated pIONT-induced orofacial mechanical allodynia and reduced ERK activation. Immunostaining showed that CCR2 and CCR3 are expressed in TG neurons, and CCL7-induced hyperexcitability of TG neurons was decreased by antagonists of CCR2 or CCR3. CONCLUSION: CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.

Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENT Itch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

An affective space view on depression and anxiety.

The circumplex model for core affect is among the most prominent characterizations of emotion and has received extensive empirical support. However, no prior study exists that connects the measurement of depression and anxiety with the core affect structure and the bipolar dimensions of arousal and valence it includes. OBJECTIVES: This study aims to investigate the reconcilability between a continuous model based on Russell's core affect system and a discrete entity view on depression and anxiety. METHODS: The data were drawn from the anxiety and depression short forms in the Patient-Reported Outcomes Measurement Information System (N = 763). It consists of 15 items with a 5-point Likert scale. Ratings of the items in terms of distress and arousal were obtained from experts in emotion research. An approach based on Russell's core affect theory was compared with the common type of factor models in which the items are lined up on clearly separated depression and anxiety dimensions with an empty space in between, as if they are separate and discrete entities. Our alternative model works with a continuous space instead. RESULTS: The core affect theory-based method exhibits a goodness of fit that is comparable with the conventional models. CONCLUSIONS: Depression and anxiety can be understood in terms of Russell's bipolar core affect model; the core affect-based model leaves room for symptoms in the space between dimensions.

New species of Cystolepiota from China.

In this paper, a new species, Cystolepiota pseudofumosifolia, is introduced. C. pseudofumosifolia is characterized by granulose or powdery pileus with an anatomic structure that is loosely globose, as well as ellipsoid cells in chains in the pileus covering the cheilocystidia. This new species is compared to the related and similar Cystolepiota species in morphology and molecular phylogeny based on Internal transcribed spacer sequences. Both types of data support our specimens as a new species in the genus Cystolepiota.

ATP synthesis is active on the cell surface of the shrimp Litopenaeus vannamei and is suppressed by WSSV infection.

BACKGROUND: Over the past a few years, evidences indicate that adenosine triphosphate (ATP) is an energy source for the binding, maturation, assembly, and budding process of many enveloped viruses. Our previous studies suggest that the F1-ATP synthase beta subunit (ATPsyn ß, BP53) of the shrimp Litopenaeus vannamei (L. vannamei) might serve as a potential receptor for white spot syndrome virus (WSSV)'s infection. METHODS: BP53 was localized on the surface of shrimp hemocytes and gill epithelial cells by immunofluorescence assay and immunogold labeling technique. Cell surface ATP synthesis was demonstrated by an in vitro bioluminescent luciferase assay. Furthermore, the expression of bp53 after WSSV infection was investigated by RT-PCR test. In addition, RNAi was developed to knock down endogenous bp53. RESULTS: BP53 is present on shrimp cell surface of hemocytes and gill epithelia. The synthesized ATP was detectable in the extracellular supernatant by using a bioluminescence assay, and the production declined post WSSV binding and infection. Knocking down endogenous bp53 resulted in a 50% mortality of L. vannamei. CONCLUSION: These results suggested that BP53, presenting on cell surface, likely served as one of the receptors for WSSV infection in shrimp. Correspondingly, WSSV appears to disturb the host energy metabolism through interacting with host ATPsyn ß during infection. This work firstly showed that host ATP production is required and consumed by the WSSV for binding and proceeds with infection process.