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PubMed1997

Effects of hypergravic fields on serotonergic neuromodulation in the rat hippocampus.

The effects of 7 day exposure to 2G fields on serotonergic modulation at two synapses on a hippocampal pathway were examined by recording dentate gyrus and CA1 pyramidal cell layer electrical activity. Serotonin decreased the amplitude of the population spike (synchronous action potentials in hundreds of neurons) in both the dentate gyrus and CA1 regions of rats exposed to 2G fields for 7 days. The inhibition, averaging 26 +/- 4% (mean +/- SEM) in the dentate gyrus and 80 +/- 5% in the CA1 region, was not significantly different from inhibitory responses observed in 1G controls. The 5-HT1A agonist 8-OH-DPAT mimicked this inhibition in the dentate and CA1 regions of 1G rats. 8-OH-DPAT responses were not affected by exposure to 2G fields. We conclude that the hippocampus contains surplus 5-HT receptors so that decreases in receptor density reported in receptor binding studies do not result in a decrease in modulatory capability. A model to account for the physiological pathway that relates gravitational field strength to 5-HT receptor density without changing the effectiveness of 5-HT neuromodulation is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

[Neuromodulation as an alternative method in the treatment of refractory angina pectoris].

Epidural stimulation of the spinal cord affects the activation of afferent nerve fibres. Patients refractory to conventional therapy of angina pectoris can be treated with epidural stimulation since 1985. The stimulation electrode is inserted by a small incision to the skin at Th4-Th5 and positioned to the epidural space at Th1-C7. The impulse generator is implanted to the lateral abdominal wall and connected to the stimulation electrode. This treatment should be restricted to patients refractory to--or not suited for--surgical and catheter-based coronary revascularisation. Clinical trials demonstrated increased exercise tolerance, reduction in severity of exertional angina and ST-depression and reduction of nitrate dosage. No impairment of overall prognosis by neuromodulation has been shown in several clinical studies. Epidural spinal cord stimulation represents an alternative therapy for the treatment of selected patients with angina pectoris refractory to conventional therapy.

Angina Pectoris↗
PubMedDate not supplied

[Temporary sacral and tibial neuromodulation in treating patients with overactive urinary bladder].

The effects of temporary sacral (S3) stimulation and posterior tibial nerve stimulation were studied in patients with the overactive urinary bladder. Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were used to treat this abnormality. There was a decrease in the average frequency of voiding, in the number of leakage episodes and used pads per day after both stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32 patients and after temporary sacral (S3) stimulation and in 14 of the patients following posterior tibial nerve stimulation. Neuromodulation is an effective treatment in patients with the overactive bladder.

Electric Stimulation↗
PubMed2001

[Zinc ions: an endogenous neuromodulator].

Zinc ions are widely distributed in the central nervous system. Zinc ions are released from neurons in a calcium-dependent manner. In recent years abundant evidence indicates that zinc ions modulate not only the release of transmitters, but also the voltage- and ligand (excitatory and inhibitory amino acids)-gated channels, suggesting that these ions may serve as an important endogenous neuromodulator.

Animals↗
PubMed2003

[The role of electrical neuromodulation in the therapy of chronic lower urinary tract dysfunction].

The electrostimulation techniques may be used as a supplement or an alternative to standard therapy. Electrical therapy for chronic lower tract dysfunction comprises of non-invasive pudendal nerve neuromodulation and invasive sacral nerve stimulation. Short-term functional electrical stimulation seems favourable in selected patients with detrusor hyperreflexia. Sacral nerve stimulation may be a successful treatment option for patients with refractory detrusor overactivity and some forms of urinary retention.

Anal Canal↗
PubMed2003

Effects of vagal neuromodulation and vagotomy on control of food intake and body weight in rats.

Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.

Afferent Pathways↗
PubMed2004

Neuromodulation paired with learning dependent practice to enhance post stroke recovery?

Over the past two decades, experimental studies following brain injury have shown that the central nervous system is dynamic and malleable to internal and external inputs. Neuromodulation and/or direct manipulation of motor and sensory experience can modify brain plasticity and functional outcome after experimental lesions. Specifically, pharmacologic modulation has been found to facilitate recovery of various behavioral deficits following occlusive injury. Additionally, the behavioral experience that induces long-term plasticity in motor and sensory maps after injury appears to be limited to those that entail the development of new skills. These data have strong application to human rehabilitation. This review will: (1) overview critical experimental studies that show that pharmacologic manipulation and/or specific behavioral experience may modify the functional organization of the injured brain and (2) review beginning studies which are exploring the application of this knowledge clinically.

Animals↗
PubMed1997

The role of the neuromodulator adenosine in alcohol's actions.

The interaction between the neuromodulator adenosine and adenosine receptors on the surface of neurons modifies the neurons' responses to neurotransmitters. The activated adenosine receptors alter the levels of small signaling molecules (i.e., second messengers) in the cells. Depending on the receptors and cells involved, these changes can make it easier or more difficult for neurotransmitters to excite the cell. Adenosine's activity is regulated by proteins called nucleoside transporters, which carry adenosine into and out of the cell. Alcohol interferes with the function of the adenosine system. For example, both acute and chronic alcohol exposure affect the function of the adenosine-carrying nucleoside transporters, thereby indirectly altering the second-messenger levels in the cells. Through this mechanism, adenosine may mediate some of alcohol's effects, such as intoxication, motor incoordination, and sedation.

Adenosine↗
PubMedDate not supplied

[Neurostimulation and neuromodulation in urinary incontinence].

Electric stimulation in Urology has undergone considerable development since the 1970s. The implantation methods for urinary system stimulation are used for bladder emptying in neurogenic bladders (Neurostimulation) or the modulation of the electrical transmission of the voiding cycle caused by chronic detrusor-sphincter dysfunction (Neuromodulation). Both techniques have in common the direct stimulation of the sacral roots, responsible for the urinary reflex arc. The first of them works via external stimulation over an implanted antenna, and the second via permanent stimulation through an implanted pacemaker. We review in this article the indications, technique and results of both therapies, specially focused on the Spanish experience.

Algorithms↗
PubMed2005

Sacral-neuromodulation CT-guided.

PURPOSE: Sacral neuromodulation is a new treatment for refractory voiding disorders such as urge incontinence, urinary retention, frequency-urgency syndromes and faecal incontinence. The current approach to sacral nerve stimulation consists of a two-stage procedure. The first is a PNE test (Percutaneous Nerve Evaluation) by a provisional electrically stimulated spinal needle, placed percutaneously in the S3 foramina for four to ten days. If successful, the second stage, permanent implantation, is carried out. The PNE test is performed under fluoroscopic control using the palpable bony sacral foramina as referral points. This technique can show some limitations, such as operator Rx exposure, poor visualization of sacral foramina because of bowel gas artefacts or sacral malformation. In order to reduce these inconveniences and to improve efficiency of the test we tried an alternative technique. The purpose of our study was to test the use of CT as an alternative technique in order to evaluate its advantages and possible routine use. MATERIALS AND METHODS: We tested 30 patients with the PNE test under CT guidance (16 males and 14 females) suffering from serious pelvic disorders and not responding to the normal therapeutic regime. Twenty-seven patients showed relative anatomical integrity of the pelvis and the sacrum, the remaining 3 patients presented morphological anomalies of the sacral foramina. With the patient in the prone position the sacral foramina were identified with CT volumetric scanning using a spiral CT scanner equipped with a second console for the three-dimensional reconstructions. Having identified the location of the S3 foramina, a sterile field was prepared and the spinal needle introduced checking correct positioning with a CT control scan. An electrode was then inserted after having checked correct muscular contractile response and the precise position with a further CT scan. RESULTS: Thirty patients were subjected to PNE under CT guidance for a total of 38 centerings. Eight patients underwent the PNE procedure on both the S3 foramina. The sacral foramen was centred at the first attempt in 36 out of 38 cases. Two cases required several attempts to centre correctly the foramen. In 4 patients out of 30 a second electrode was implanted. In one patient who had a nonconsolidated sacral fracture, CT guidance enabled insertion of the electrode inside the only practicable foramen, a manoeuvre that would have been impossible with fluoroscopical guidance. Only once was the electrode placed in a wrong location but promptly repositioned after a CT control. During the whole trial period we had a positive response to the PNE test in 18 out of 30 patients (60%), a partial response in 4 out of 30 patients and a negative response in the remaining 8 patients. None of the patients who underwent the PNE test had infectious complications and the procedure was well tolerated by all. The procedure lasted about 45 minutes.

Adult↗
PubMed2005

[Cystomanometric study of bladder sensation during sacral neuromodulation test].

PURPOSE: Prospective clinical and urodynamic study evaluating modification of bladder sensation during sacral neuromodulation (SNM). MATERIALS AND METHODS: 24 consecutive patients with non-neurological hyperactive bladder underwent an SNM test. Questioned about their symptoms before and during the test by the urinary handicap assessment scale, patients were divided into two groups: A (improved) and B (not improved). Group A consisted of patients obtaining 50% improvement of their symptoms with SNM followed by return of symptoms at the end of the test, while the other patients constituted group B. We then compared the cystomanometric results according to their clinical response. RESULTS: The mean age was 53 years: 10 patients with a good response constituted group A (n=10, i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e. 58%). Clinically, in patients with a good response, SNM decreased urge incontinence by 100%, day-time frequency by 89% and protections by 55%. Urodynamic assessment in group A during the test demonstrated a significant increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the first unstable contraction (p<0.004), +83% of bladder volume to the first urge to urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in 100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3 in 58% of non-improved subjects. No significant difference of intensity of unstable contractions was observed between the 2 groups during SNM (p=0.31). CONCLUSION: A significant correlation was observed between the two methods of clinical and urodynamic assessment. Our results suggest the use of the cystomanometric increase of bladder volume at B1 and B3 as selection criterion for candidates for SNM with non-neurological hyperactive bladder.

Aged↗
PubMedDate not supplied

[The role of somatosensory evoked potentials in prognosis of efficacy of tibial neuromodulation in patients with hyperactive urinary bladder].

Registration of evoked brain potentials was used as a non-invasive and an objective method of diagnosis of the CNS diseases. Somatosensory evoked potentials (SSEP) in response to stimulation of the tibial nerve were studied in patients with hyperactive urinary bladder (HUB) to clarify SSEP role in prognosis of tibial neuromodulation (TNM) efficacy. Urodynamic parameters and SSEP were examined in 13 patients with symptoms of urinary accumulation disorders. Neurogenic HUB was diagnosed in 6 patients, idiopathic one--in 7 patients. TNM was delivered in 30-min weekly sessions (n = 12). Six of seven patients with a cortical potential responded to TNM. Of six cortical nonresponders a positive result was achieved only in two. Thus, patients with the cortical potential demonstrate better effect of TNM than those without the potential. It is suggested that TNM influences both sacral and supraspinal center of urination.

Adult↗
PubMed2002

Neuromodulation for the treatment of refractory interstitial cystitis.

Interstitial cystitis (IC) is a symptom complex of urinary urgency, frequency and pelvic pain. Multimodality behavioral and phamacologic treatment is often effective in treating IC. Unfortunately, some patients with IC are refractory to standard treatments. Neuromodulation has been shown to be effective in treating voiding dysfunction. Small studies have demonstrated improvement in pelvic pain and IC symptoms during temporary sacral nerve stimulation. This current study demonstrates that patients refractory to traditional therapies for IC can respond well to sacral nerve stimulation and maintain improvement in symptoms after permanent implantation of a neurogenerator. The technique used to place the neurostimulator can impact on the degree of the response and the complication rate. Sacral neurostimulation continues to evolve and should be in the armamentarium available to treat voiding dysfunction.

Journal Article↗
PubMed1992

[Initial experiences with neuromodulation as treatment for incontinence and micturition disorders in The Netherlands].

Neuromodulation is a new treatment modality for disturbances of bladder function. By stimulation of a sacral nerve the pelvic floor is activated, thus affecting the reflex arcs which control micturition and continence. Along with 2 case histories the methods of the preoperative percutaneous test stimulation and the implantation of stimulator and electrode are described.

Adult↗
PubMedDate not supplied

Neuromodulative actions of cytokines.

Interleukin 1, interferon alpha 2, and tumor necrosis factor alpha are cytokines that centrally mediate various reactions typical of the host defense responses to infection. The preoptic-anterior hypothalamus is an important, but not exclusive, integrative and controlling region for several of these effects. Although these cytokines display some common functional activities (e.g., pyrogenicity, somnogenicity), the characteristics of the responses they induce are different. Their effects, moreover, can be evoked or suppressed selectively, indicating that the neuronal substrates and/or neuromodulators used are distinct, each possessing discrete but partially overlapping sensory combinations. Nevertheless, it is not yet obvious how these systems are organized and integrated in host defense. It is also unclear whether these cytokines are elaborated peripherally and gain access to the brain or whether they are induced centrally. The available data suggest that circulating cytokines probably do not penetrate the brain but may activate elements in the organum vasculosum laminae terminalis. This site appears to be critically important for the production of the centrally mediated effects of blood-borne cytokines; it is speculated that the cytokines evoke there local signals that transduce their message; serotonin may be linked to these signals.

Animals↗
PubMed1990

Neuromodulation of the crab pyloric central pattern generator by serotonergic/cholinergic proprioceptive afferents.

In the stomatogastric nervous system of the crab, Cancer borealis, a set of 4 serotonergic/cholinergic proprioceptive neurons, called gastropyloric receptor (GPR) cells, have effects on the pyloric motor pattern. In a semi-intact foregut preparation, the GPR cells are not activated by movements of the pyloric filter; instead they respond to the slower movements of the gastric mill (Katz et al., 1989). Thus, their activity is not synchronized to the pyloric motor pattern. However, when the GPR cells are stimulated in an in vitro preparation in a manner that resembles their normal firing pattern, they produce dramatic effects on the pyloric motor pattern. These effects include: (1) a prolonged increase in the pyloric cycle frequency, (2) a momentary pause in the motor pattern, (3) transient inhibition of some motor neurons, (4) strong excitation of other motor neurons, and (5) altered phase relationships of the different components of the motor pattern. These changes in the motor pattern are due to direct effects of the GPR cells on neurons in the pyloric central pattern generator (CPG). All of the cells in the pyloric circuit appear to receive GPR input. However, only 2 neurons receive detectable rapid nicotinic synaptic potentials. The other neurons receive only slower neuromodulatory input from GPR stimulation. The neuromodulatory effects include burst enhancement, plateau potential enhancement, excitation, and inhibition. These modulatory effects are largely mimicked by bath-applied serotonin (5-HT). Thus, primary sensory neurons can alter the production of motor patterns by a CPG through a phase-independent mechanism; these proprioceptors do not need to fire at a precise time in the cycle to be effective because their effects are mediated through the slower actions of the neuromodulator 5-HT.

Animals↗
PubMed1989

Vasopressin neuromodulation in the hippocampus.

This study explored an effector mechanism associated with the arginine vasopressin (AVP) recognition site in the hippocampus, namely, potentiation of norepinephrine (NE)-induced cAMP accumulation in the surviving hippocampal slice. The biochemical mechanisms that underlie the AVP potentiation were investigated as follows: First, the actions of AVP upon NE-induced accumulation of cAMP in hippocampal slices from rat brain were specific to AVP and not shared by other closely related peptides, namely, oxytocin and AVP4-9. Second, the AVP-induced neuromodulation involved beta-adrenergic receptors, with AVP having no effect on cAMP levels in the absence of NE. Third, the potentiation by AVP was biphasic, with lower AVP concentrations potentiating NE-induced cAMP accumulation, while higher concentrations did not potentiate. Fourth, an antagonist of V1-type AVP receptors blocked AVP potentiation. Fifth, AVP potentiation was dependent upon extracellular calcium concentrations. Sixth, AVP potentiation was blocked by 50 microM trifluoperazine, which is consistent with a calcium-calmodulin involvement but which might also implicate protein kinase C. These alternatives and the nature of the calcium involvement are discussed. AVP actions thus appear to involve interactions between several second-messenger systems and suggest a biochemical mechanism by which AVP exerts its centrally mediated behavioral effects.

Adrenergic beta-Agonists↗