Background
Both early life stress and neuropathic pain induce morphological and functional abnormalities of the nervous system that are associated with emotional regulation. In our previous study, ...early life stress enhanced nerve injury‐induced hyperalgesia in adult male and female mice. In the present study, using phosphorylated extracellular signal‐regulated kinase (p‐ERK) as a marker of neuronal activation, we examined the effect of early life stress on neuronal function following partial sciatic nerve ligation (PSL).
Methods
Early life stress was induced by maternal separation from 2 to 3 weeks of age and by social isolation after weaning (MSSI). Neuropathic pain was induced by PSL at 9 weeks of age, and p‐ERK expression after light touch stimulation to the ipsilateral paw was measured using immunohistochemistry 1 week after nerve injury.
Results
Although MSSI increased p‐ERK expression in the paraventricular nucleus (PVN) and amygdala of male mice, PSL did not affect p‐ERK expression in control and MSSI mice. In female mice, increased p‐ERK expression was observed in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Furthermore, p‐ERK expression in the PVN and amygdala was increased in MSSI‐PSL mice.
Conclusions
The present data suggest that early life stress sex‐dependently and site‐specifically increases neuronal activity in the brain. In addition, increased neuronal activity in multiplebrain regions of mice subjected to early life stress may enhance hyperalgesia after nerve injury.
What does this study add?
Maternal separation and social isolation (MSSI) increased p‐ERK in the paraventricular nucleus (PVN) and amygdala of male mice. MSSI increased p‐ERK in the medial prefrontal cortex and nucleus accumbens of female mice. Neuropathic pain increased p‐ERK in the PVN and amygdala of female MSSI mice.
Background and Purpose
The ω‐3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic ...acid‐induced antinociception may be mediated by the orphan GPR40, now identified as the free fatty acid receptor 1 (FFA1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons.
Experimental Approach
Formalin‐induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5‐HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c‐Fos was estimated by immunohistochemistry, and the levels of noradrenaline and 5‐HT in the spinal cord were measured by LC‐MS/MS.
Key Results
FFA1 receptors colocalized with NeuN (a neuron marker) in the medulla oblongata and with tryptophan hydroxylase (TPH; a serotonergic neuron marker) and dopamine β‐hydroxylase (DBH; a noradrenergic neuron marker). A single i.c.v. injection of GW9508, a FFA1 receptor agonist, increased the number of c‐Fos‐positive cells and the number of neurons double‐labelled for c‐Fos and TPH and/or DBH. It decreased formalin‐induced pain behaviour. This effect was inhibited by pretreatment with 6‐hydroxydopamine, DL‐p‐chlorophenylalanine, yohimbine or WAY100635. Furthermore, GW9508 facilitated the release of noradrenaline and 5‐HT in the spinal cord. In addition, GW1100, a FFA1 receptor antagonist, significantly increased formalin‐induced pain‐related behaviour.
Conclusion and Implications
Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system.
No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination.
To identify a reliable marker for the clinical ...diagnosis of MM2-type sCJD.
CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses.
The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on 18F2-fluoro-2-deoxy-d-glucose PET.
For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or 18F2-fluoro-2-deoxy-d-glucose PET for the thalamic form.
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