MicroRNA-mediated downregulation of potassium-chloride-cotransporter and vesicular γ-aminobutyric acid transporter expression in spinal cord contributes to neonatal cystitis-induced visceral pain in rats.

Loss of GABAergic inhibition in pain pathways has been considered to be a key component in the development of chronic pain. In the present study, we intended to examine whether miR-92b-mediated posttranscriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid transporter (VGAT) plays a major role in the development and maintenance of long-term visceral hyperalgesia in neonatal zymosan-treated rats. Neonatal cystitis was induced by transurethral zymosan administration from postnatal (P) days 14 to 16 (protocol 1).

Analgesic effect of ADX71441, a positive allosteric modulator (PAM) of GABA receptor in a rat model of bladder pain.

Therapeutic use of GABA receptor agonists for conditions like chronic abdominal pain, overactive bladder (OAB) and gastroesophageal reflux disease (GERD) is severely affected by poor blood-brain barrier permeability and potential side effects. ADX71441 is a novel positive allosteric modulator (PAM) of the GABA receptor that has shown encouraging results in pre-clinical models of anxiety, pain, OAB and alcohol addiction. The present study investigates the analgesic effect of ADX71441 to noxious stimulation of the urinary bladder and colon in rats.

Percutaneous electrical nerve field stimulation modulates central pain pathways and attenuates post-inflammatory visceral and somatic hyperalgesia in rats.

A non-invasive, auricular percutaneous electrical nerve field stimulation (PENFS) has been suggested to modulate central pain pathways. We investigated the effects of BRIDGE® device on the responses of amygdala and lumbar spinal neurons and the development of post-colitis hyperalgesia. Male Sprague-Dawley rats received intracolonic trinitrobenzene sulfonic acid (TNBS) and PENFS on the same day.

Neonatal bladder inflammation induces long-term visceral pain and altered responses of spinal neurons in adult rats.

Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats.

Role of principal ionotropic and metabotropic receptors in visceral pain.

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life.

NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation.

NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.

Analgesic effect of minocycline in rat model of inflammation-induced visceral pain.

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment.

Visceral analgesic effect of 5-HT(4) receptor agonist in rats involves the rostroventral medulla (RVM).

The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate visceral pain. However, the underlying mechanism remains unknown. The objective of the present study was to examine the analgesic mechanism and site of action of TEG.

MicroRNA-mediated GABA Aα-1 receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats.

The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system.

Protective effect of hesperidin, a citrus flavanoglycone, against γ-radiation-induced tissue damage in Sprague-Dawley rats.

The present study was designed to evaluate the radioprotective effect of hesperidin, a citrus flavanoglycone, against γ-radiation-induced cellular damage in the liver, heart, and kidney of rats. Whole-body γ-radiation exposure (5 Gy) of healthy adult rats resulted in cellular damage and oxidative stress manifested as increased levels of serum marker enzymes, lipid peroxidation, and fibrosis in the tissues, accompanied by depletion of cellular glutathione and abnormal alteration in the levels of lysosomal enzymes. Treatment with hesperidin (50 and 100 mg/kg, p.

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats.

Diethylnitrosamine (DEN), found in many commonly consumed foods, is widely reported to induce cancer in animals and humans. The aim of the present study was to investigate the hepatoprotective and antioxidant activities of the leaf extract of the medicinal plant Cassia fistula Linn. against diethylnitrosamine induced liver injury in ethanol pretreated rats.

Absorption, distribution, excretion, and pharmacokinetics of 14C-pyronaridine tetraphosphate in male and female Sprague-Dawley rats.

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) of 14C-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.

Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats.

Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.

Silymarin modulates the oxidant-antioxidant imbalance during diethylnitrosamine induced oxidative stress in rats.

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence, there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of silymarin as a hepatoprotective and an antioxidant against diethylnitrosamine induced hepatocellular damage.

Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats.

The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.

Influence of silymarin administration on hepatic glutathione-conjugating enzyme system in rats treated with antitubercular drugs.

Objective: This study evaluated the influence of simultaneous administration of silymarin (SIL), a hepatoprotective and antioxidant agent, on the status of glutathione (GSH) and its metabolising enzymes in the liver tissue of rats treated with antitubercular drugs, i.e. isoniazid (INH), rifampicin (RIF) and pyrazinamide (PYR).