Neurochemical research
-
Neurochemical research · May 2015
Activated microglia contribute to convergent nociceptive inputs to spinal dorsal horn neurons and the development of neuropathic pain.
The activation of microglia in the spinal dorsal horn following peripheral nerve injury has been reported previously, and this change has been proposed to contribute to the development of a neuropathic pain state. We recently demonstrated that peripheral nerve injury activated convergent nociceptive inputs to spinal dorsal horn neurons. The present study was designed to further examine the role of microglia in the activation of convergent nociceptive inputs as well as development of a neuropathic pain state after peripheral nerve injury. ⋯ The same minocycline treatment (day 0-7) also reduced the nerve injury-induced convergence of nociceptive inputs to spinal dorsal horn neurons, as revealed by double immunofluorescence labeling for c-Fos induced by noxious heat stimulation of the hindpaw and phosphorylated extracellular signal-regulated kinase induced by electrical stimulation of the injured tibial nerve. However, the administration of minocycline for 8 days starting 7 days after surgery did not prevent nerve injury-induced microglial activation, convergent nociceptive inputs, or tactile and thermal hypersensitivity. These results suggest that microglial activation in the early stage following peripheral nerve injury plays an important role in the anomalous convergence of nociceptive signals to spinal dorsal horn neurons and the development of neuropathic pain.
-
Neurochemical research · May 2015
S100B and Glial Fibrillary Acidic Protein as Indexes to Monitor Damage Severity in an In Vitro Model of Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading and rising cause of death and disability worldwide. There is great interest in S100B and Glial Fibrillary Acid Protein (GFAP) as candidate biomarkers of TBI for diagnosis, triage, prognostication and drug development. However, conflicting results especially on S100B hamper their routine application in clinical practice. ⋯ Consequently, the total amount of GFAP released showed a strong linear relationship with the severity of injury (R(2) = 0.7662; p < 0.001). Under these experimental conditions, S100B seems to be useful in diagnosing only moderate to severe TBI-like injuries. Differently, GFAP demonstrates adequate biomarker requisites since its cellular release is affected by all grades of injury severity.
-
Neurochemical research · Apr 2015
Nonvesicular release of ATP from rat retinal glial (Müller) cells is differentially mediated in response to osmotic stress and glutamate.
Retinal glial (Müller) cells release ATP upon osmotic stress or activation of metabotropic glutamate receptors. ATP inhibits the osmotic Müller cell swelling by activation of P2Y1 receptors. In the present study, we determined the molecular pathways of the ATP release from Müller cells in slices of the rat retina. ⋯ The p-glycoprotein blocker verapamil had no effect. As revealed by single-cell RT-PCR, subpopulations of Müller cells expressed mRNAs for pannexin-1 and -2, and connexins 30, 30.3, 32, 43, 45, and 46. The data may suggest that rat Müller cells release ATP by multidrug resistance channels, CFTR, and connexin hemichannels in response to osmotic stress, while glutamate induces a release of ATP via multidrug resistance channels, connexin hemichannels, and pannexin-1.
-
Neurochemical research · Apr 2015
IL-10 and IL-1β mediate neuropathic-pain like behavior in the ventrolateral orbital cortex.
Previous evidence has shown that the glial cells can be activated by peripheral nerve injury and release both pro-inflammatory and anti-inflammatory cytokines, which play crucial roles in the establishment and maintenance of neuropathic pain. The present study examined the roles of anti-inflammatory cytokine IL-10 and pro-inflammatory IL-1β on allodynia induced by spared nerve injury (SNI) in the ventrolateral orbital cortex (VLO) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. ⋯ Moreover, western blotting results showed expression levels of IL-10 and IL-1β significantly up-regulated in the contralateral VLO of SNI rats as compared with that of sham-operated rats. These results suggest that anti-inflammatory cytokine IL-10 and pro-inflammatory cytokine IL-1β mediate neuropathic-pain like behavior at the cerebral cortex level; IL-10 released from activated glial cells in the VLO can potentially attenuate allodynia while IL-1β released from activated glial cells in the VLO can potentially maintain or facilitate allodynia. These results provide new insights and site for therapy at the cerebral cortex level in neuropathic pain condition.
-
Neurochemical research · Mar 2015
Suppression of microRNA-155 attenuates neuropathic pain by regulating SOCS1 signalling pathway.
Chronic neuropathic pain is an unfavourable pathological pain characterised by allodynia and hyperalgesia which has brought considerable trouble to people's physical and mental health, but effective therapeutics are still lacking. MicroRNAs (miRNAs) have been widely studied in the development of neuropathic pain and neuronal inflammation. Among various miRNAs, miR-155 has been widely studied. ⋯ Furthermore, knockdown of SOCS1 abrogated the inhibitory effects of miR-155 inhibition on neuropathic development and neuronal inflammation. Finally, we demonstrated that inhibition of miR-155 resulted in the suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation by mediating SOCS1. Our data demonstrate the critical role of miR-155 in regulating neuropathic pain through SOCS1, and suggest that miR-155 may be an important and potential target in preventing neuropathic pain development.