THE INFLUENCE OF MONTELUKAST ON THE ACTIVITY OF THE AUTONOMIC NERVOUS SYSTEM ESTIMATED BY HEART RATE VARIABILITY IN EXPERIMENTAL PARTIAL BLADDER OUTLET OBSTRUCTION IN RATS.

Due to their paracrine action, leukotrienes released from the urothelium are involved in control of the bladder function. Anti-leukotriene agents appear to exert an ameliorating effect in bladder overactivity. It is unknown, whether their possible, modulatory impact on the autonomic nervous system (ANS) activity may also contribute to the potentially beneficial effect of those compounds. Therefore, our aim was to indirectly estimate the ANS function using the heart rate variability (HRV) study in rats with experimental partial bladder outlet obstruction (PBOO), reflecting human benign prostatic hyperplasia (BPH), treated with leukotriene receptor antagonist - montelukast (MLKT). Twenty rats with surgically induced PBOO lasting for 14 days, divided into two groups: group 1 (10 control subjects) and group 2 (10 MLKT-treated rats; 2 mg/rat/day) were subjected to HRV recordings, preceded by daily urine collection and a subsequent cystectomy with histopathological evaluation of collected bladders. Standard HRV time and spectral parameters were calculated. MLKT-treated animals demonstrated an increase in power of non-normalized LF (low frequency) and HF (high frequency) components with no change of the total HRV power. Moreover, an increase and decrease in normalized nLF and nHF, respectively, were assessed in those animals compared to the control. Additionally, a decrease in daily diuresis measurement was demonstrated in MLKT-treated animals. Montelukast treatment resulted in the functional ANS status re-arrangement, with sympathetic overdrive and parasympathetic withdrawal. Those changes may contribute to alleviation of bladder overactivity symptoms, independently on leukotriene receptors blockade.

The influence of prostaglandin PGE1 and PGF2alpha analogues on autonomic nervous system activity, estimated with heart rate variability, in cyclophosphamide-induced hemorrhagic cystitis in rats.

UNLABELLED: The cyclophosphamide-induced hemorrhagic cystitis (CP-HC) is a common consequence of cyclophosphamide treatment with complex pathophysiology involving several inflammatory mechanisms and autonomic nervous system dysregulation. THE AIM OF THIS STUDY: To determine effects of prostaglandin PGE1 and PGF2alpha analogues on the activity of the autonomic nervous system (ANS), estimatedindirectly on the basis of heart rate variability (HRV), in an experimental model of cyclophosphamide-induced hemorrhagic cystitis (CP-HC). Moreover we verified if potential changes in autonomic regulation can contribute to uroprotective role of prostaglandins. MATERIAL AND METHODS: The study included three groups of rats with experimentally induced CP-HC. The animals from group 2 and 3 were administered PGE1 and PGF2a analogues, respectively, and the rats from group 1 (controls) did not receive any treatment. The HRV of animals from all the groups was analyzed after seven days of the experiment. RESULTS: Administration of both PGF2alpha and PGE1 was associated with an increase in the power of VLF component and total power on frequency-domain analysis. Moreover, a significant increase in the power of non-normalized components, LH and HF, and two parameters of time-domain analysis, SDN-N and rMSSD, was documented in PGF2alpha-administered animals. Both prostaglandin-treated groups did not differ significantly from the controls in terms of the values of normalized parameters, nLF and nHF. CONCLUSIONS: The analyzed prostaglandin analogues increased total autonomic activity but did not induced preferential changes in sympathetic or parasympathetic activity. Nevertheless, the VLF changes documented on HRV analysis may reflect a decrease in the level of certain pro-inflammatory mediators, thus pointing to, previously postulated in literature, potential beneficial uroprotective effect of prostaglandins in CP-HC.

Effects of vagus nerve stimulation in visceral pain model.

Visceral pain is an important therapeutic problem. A number of studies have established that abdominal vagal afferents modulate somatic pain behavior. Although it is not clear if vagal afferents transmit nociceptive information, a change in their activity can increase or decrease nociceptive transmission in visceral pain. Aims of the present study were to determine whether the subdiaphragmatic vagus nerves play a role in the endogenous pain inhibitory mechanisms in visceral pain model and whether it involves opioidergic pathways. Data obtained in our studies show that vagus nerve plays the direct role in conveying the nociceptive information in the peritonitis model of visceral pain. We have shown, that vagal afferents exhibit an increase in excitability and subdiaphragmatic vagotomy decrease nociceptive behavior in visceral pain in rats. We have also tested two different stimulation parameters of chronic subdiaphragmatic vagal nerve stimulation: VNS1 (high-intensity) and VNS2 (low-intensity) in visceral pain model in rats. Both stimulation parameters increased pain threshold but VNS1 was more effective than VNS2. Naloxone inhibited the antinociceptive effects of VNS, reversing partially increase in the pain threshold in rats and increases number of writhes in visceral pain model. Therefore, our data indicate that this analgesic effect of the VNS is mediated, at least in part, by descending opioidergic pathways. The present study has confirmed the importance of vagal afferents for nociception in general and proven that this role is not limited to somatic pain but also extends to visceral pain.

Pentoxifylline modifies central and peripheral vagal mechanism in acute and chronic pain models.

The inflammatory process gives the way to hyperalgesia that is documented by the animal experimental studies. Pentoxifylline (PTX) has strong antyinflamatory effects, decreases TNF-alpha and other proinflammatory cytokines production. Therefore, the aim of present investigation was to evaluate the effectiveness of PTX in nociception processes, especially in aspects of vagal activity, in experimental pain models: visceral pain (VP), neuropathy (CCI) and neurogenic inflammation (NI). In VP and CCI models we observed significant increase in the pain threshold after blocking proinflammatory cytokines whereas in NI there was no such effect. In our studies we also observed the increase of vagal afferents activity in VP and CCI, on the contrary to NI model. In summary, our study demonstrates that preemptive inhibition of proinflammatory cytokine synthesis by treatment with PTX is useful in antagonizing hyperalgesia in inflammatory pain. Pentoxifylline reduces central and peripheral sensitization processes depend on the vagal component in both acute and chronic pain models but in a different manner and mechanisms. Our results establish the participation of inflammatory and vagal component in nociception. The modulation of the vagal system offers the new possibilities of the pain treatment in patients resistant to the classical analgesic therapy.

[Vagal modulation of nociception in experimental model of viscreal pain]. / Rola nerwu blednego w doswiadczalnym modelu bólu trzewnego.

Systemic control mechanisms of pain are based on interplay between nervous autonomic and immune systems. The aim of this study was to examine a possible role of the vagus nerve in regulation of nocyception. Peritoneal inflammation increased vagal activity. Pretreatment of PTX had an analgesic effect confirmed by amount of WT and decreased vagal activity. The vagotomy decreased nociceptive threshold.

[Role of pendoxifiline (PTX) in different and cute and chronic models of pain in rats]. / Rola pentoksyfiliny (PTX) w wybranych ostrych i przewleklych modelach bólowych u szczurów.

Pentoxifilne (PTX) is a non specific inhibitor of cytokines release, which suppress mainly TNF production. The aim of this study was to evaluate behavioural activity changes in response to acute and chronic nociceptive stimulus. PTX was more effective in neuropathic pain than acute pain model. Use of cytokine inhibitors might offer new strategies of drug-resistant chronic pain treatment.

[Effects of melatonin on nociception processes in experimentally model of neurophatic pain]. / Wplyw melatoniny na procesy nocycepcji w doswiadczalnym modelu bólu neuropatycznego.

Melatonin (MT) plays an important role in the regulation of physiological and neuroendocrine functions, such as control of circadian rhythms and synchronization of seasonal reproductive rhythms in mammals. Melatonin shows its antinocieeptive effects in a dose - dependent manner. Melatonin is influencing the mechanical allodynia but not thermal hyperalogia. Antinociceptive effects of melatonin are having the significant connection with the MT2 receptor stimulation and activation of the opioid system.

[The role of vagal afferents in visceral hyperalgesia]. / Udzial nerwów blednych w hiperalgezji trzewnej.

The visceral sensation from the abdomen are delivered continuously to the brain by the vagus nerve, the largest visceral sensory nerve in the body. Although it is commonly assumed that vagal afferents are not involved in nociception and pain, there is growing evidence that they play a complex role in these processes. Vagal afferents may contribute to the effective-emotional rather than to the sensory-disciminative aspect of pain.

Myoelectrical activity of small intestine in rats with experimental Parkinson's disease.

Gastrointestinal (GI) motility is governed by enteric nervous system being under surveillance of central and autonomic representation. In Parkinson's disease (PD) GI dysmotility has been attributed in part to peripheral action of neurotoxines. We evaluated the effect of chronic salsolinol administration on intestinal myoelectrical activity (IMA) during fasting and in response to gastric distension (GD) in rats. Fasting IMA recordings didn't reveal differences in frequency of migrating myoelectrical complexes (MMC) (p = 0.06) and dominant frequency (DF) of slow waves (p = 0.1) between salsolinol and saline group. However in response to gastrointestinal stimulation with GD in the salsolinol group DF of IMA remained unchanged whereas in the controls increased (p = 0.04). The results suggest the direct effect of salsolinol on gastro-duodenal reflexes in PD rats.

Gastric stimulation is effective in reversing vasopressin induced gastroparesis.

UNLABELLED: The aim of this study was to determine the most effective current parameters reversing vasopressin (VP) induced gastroparesis by gastric electrical stimulation IGES). METHODS: Twenty male healthy Wistar rats were included into the study (weight 227 +/- 24 g). Animals were subjected to gastric fistula placement and implantation of two monopolar electrodes for EGG-studies and GES. After 5 days of recovery VP was applied (terlipressin 0.1 mg/kg i.p.) The gastric motility was measured by means of balloon introduced into the stomach through the fistula. The gastric electrical and motor activity were recorded by the PowerLab/8SP system and software. Electrical signals were cleared by 3000 AC/DC differential amplifier A-M System Inc. Gastric electrical stimulation (GES) was generated by Zimmer stimulator SINUS5. The following currents: S01 (monopolar): ampl 2.2 mA, freq 29 Hz, on/off 1 s / 10 s; S02 (bipolar): ampl 2.2 mA, freq 29 Hz, on/off 1s/10s: S03 (monopolar): ampl 2.2 mA, freq 0.5 Hz: S04 (monopolar): ampl 2.2 mA, freq 34 Hz, on/off 5.5 s/15 s were used. RESULTS: The phasic contractions almost disappeared and amplitude decreased from 12 +/- 5 to 2.9 +/- 1.5 cm H20. The motility index decreased from 276,3 +/- 76.4 to 154.6 +/- 63 cm H2O x s/min. GES S01-S04 increased motility index to: 167.6 +/- 60.8: 155.1 +/- 89.3; 170.3 +/- 92.3: 301.9 +/- 70.5 cm H2O x s/min respectively. The frequency of gastric slow wave increased from 0.04 +/- 0.02 to 0.07 +/- 0.02 Hz after VP administration. GES S01-S04 reversed VP induced increase of slow wave frequency to 0.06 +/- 0.02, 0.055 +/- 0.02, 0.06 +/- 0.01 and 0.04 +/- 0.02 Hz, respectively. CONCLUSIONS: This effectiveness of local GES and the pressure pattern of induced gastroparesis suggest peripheral complex inhibitory-excitatory action of vasopressin on gastric smooth muscles. The mechanism of this action may involve the enteric nervous system, gastric and vasal smooth muscles. The most effective in reversing VP induced functional gastroparesis is high frequency current applied in timing of the natural slow wave.

Effect of bowel decontamination with metronidazole and vancomycin on gastroduodenal myoelectric activity.

UNLABELLED: It is well recognized that prolonged antibiotic therapy leading to gut decontamination often results in side effects and may lead to colonization of gut with pathologic bacteria. Changes of a gut microflora could play a role in dysmotility of gastrointestinal tract. The aim of the study was to evaluate influence of intraluminal colon anaerobic and aerobic bacterial flora on myoelectric activity of duodenum and stomach. A myoelectric activity recordings using electrodes implanted on small bowel of the conscious rats were performed. Group I was scheduled for control recording, group II for recordings in 4th day after metronidazole (M) administration (30 mg/kg) and group III for recordings after vancomycin (V) administration (15 mg/kg) respectively. Rat's stools were cultured for confirmation of changes in colon flora composition. Recordings were previously filtered digitally with bandwidth filter 0.01-0.1 Hz and 0.1-1.0 Hz to extract gastric and duodenal slow wave respectively and than analyzed with Fast Fourier Transformation. Baseline duodenal slow wave frequency in control group revealed 0.60 +/- 0.05 Hz. M increased slow waves frequency to 0.64 +/- 0.13 Hz and V did not 0.58 +/- 0.09 Hz (p > 0.05). Slow wave dominant frequency of the stomach showed decrease of frequency from control 0.035 +/- 0.04 to 0.025 +/- 0.06 Hz after M (p < 0.05). Pretreatment with V also did not influence slow wave dominant frequency in comparison to control group (0.036 +/- 0.07 Hz, p > 0.05). CONCLUSION: Only pretreatment with M significantly decreased gastric slow wave frequency. One can speculate that M effects are related not only to gut decontamination but also directly affects ENS. We propose hypothesis that M influence on slow wave frequency may be related not only to its antimicrobial activity but to its potential neurotoxic action on intramural ENS neurons.