The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters and receptors expression, and modification of neuronal function. Studies indicate the involvement of MicroRNA (miRNA)-mediated transcriptional deregulation in pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatally zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenge groups) or on P30 following a zymosan re-challenge on P29 (re-challenge groups). miRNA arrays and Real-time reverse transcription polymerase chain reaction revealed significant, but differential, upregulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline controls in both unchallenge and re-challenge groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABAA receptor subunit GABAAα−1 gene with a miRSVR score of −1.83. Increase in miR-181a concomitantly resulted in significant downregulation of GABAAα−1 receptor subunit gene and protein expression in adult spinal cords from neonatal cystitis rats. Intrathecal administration of GABAA receptor agonist muscimol failed to attenuate viscero-motor response (VMR) to colon distension in neonatal cystitis rats, whereas, in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of GABAergic system in neonatal cystitis-induced chronic pelvic pain.

Results document that in rats LGG can attenuate neonatally induced chronic visceral pain measured in adulthood. Prolonged intake of LGG alters some key brain neurotransmitters and biogenic amines that could be involved in pain modulation.

Background We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices. Methods In molecular study, we examined GluA1 and GluA2 expression and phosphorylation in membrane preparations and in the isolated postsynaptic densities (PSDs) from rats receiving acute esophageal exposure of either saline (control group) or 0.1 NHCl (experimental group). In electrophysiological study, the effect of selective AMPA receptor (Ca2+ permeable) antagonist IEM-1460 and CaMKII inhibitor KN-93 was tested on responses of cortical neurons during acid infusion to address the underlying molecular mechanism of acid-induced sensitization. Key Results The acid exposure significantly increased expression of GluA1, pGluA1Ser831, and phosphorylated CaMKIIThr286, in the cortical membrane preparations. In isolated PSDs, a significant increase in pGluA1Ser831 was observed in acid-treated rats compared with controls. Microinjection of IEM-1460 or KN-93 near the recording site significantly attenuated acid-induced sensitization of cortical neurons. Conclusions & Inferences The underlying mechanism of acid-induced cortical sensitization involves upregulation and CaMKII-mediated phosphorylation of GluA1. These molecular changes of AMPA receptors subunit GluA1 in the cortical neurons might play an important role in acid-induced esophageal hypersensitivity.

Parkinson's disease is a progressive neurodegenerative disease characterized by tremors and bradykinesia (slowing of movement and speed) all due to the loss of dopamine levels in the brain. The loss of dopamine containing neurons in the brain becomes progressive and affects different parts of the brain. Dopamine is essential to the brain as dopamine enables neurons to communicate and control movement, which is lacking with Parkinson’s Disease. In Parkinson’s, the neurons are vulnerable to degeneration because of its extensive amount of energy with its vast systems of neurons. As Parkinson’s currently has no cure, the vast majority of the Parkinson’s Population is experiencing death at quick rates as short term solutions are not able to become long term. This review article sheds light on the disease progress of Parkinson’s, possible therapies with visual and auditory cueing at the main focus, and the studies effects on the treatment and scientific research progression on Parkinson’s Disease.