Long-lasting Electrical Stimulation Research Articles

Effects of different stimulus locations on inhibitory responses in human jaw-closing muscles

The aim of this study was to examine the inhibitory responses in bilateral masseter and temporalis muscle activity when electrical stimulation with short or long duration was applied to six oro-facial locations. The exteroceptive suppression period (ES2) and inhibitory responses were recorded in the surface electromyogram (EMG) of bilateral masseter and temporalis muscles in 16 healthy subjects. Two stimulus durations (1 ms single pulse and 450 ms pulse train) adjusted to a perceived intensity of 7 (distinct painful) on a 0-10 Numerical Rating Scale (NRS) were applied to the following six oro-facial locations on the right side while the subject was biting at 50% of the maximal voluntary contraction: masseter muscle, temporalis muscle, temporomandibular joint, infraorbital nerve, supraorbital nerve, and mental nerve. The stimulus intensity required to reach an NRS score of 7 was significantly lower for 450 ms train stimuli than for 1 ms single stimuli (P<0·001). There were no significant differences in the magnitude of ES2 suppression among the six different locations (P>0·876) for the 1 ms single stimuli. There were significant decreases in Root-Mean-Square-EMG values in the 400-500 ms post-stimulus epoch compared with the pre-stimulus epoch (P<0·023) for 450 ms train stimuli, but there were no significant differences in the magnitude of inhibition among the six different locations (P<0·893). Short- and long-lasting electrical stimulation of various oro-facial locations induces similar bilateral inhibitory effects in the jaw-closing muscles but with different propensity which may reflect the somatotopic organisation of these responses.

How Epilesy Changes Sodium Channels.

Induction of Neonatal Sodium Channel II and III α-Isoform mRNAs in Neurons and Microglia After Status Epilepticus in the Rat Hippocampus Aronica E, Yankaya B, Troost D, van Vliet EA, Lopes da Silva FH, Gorter JA Eur J Neurosci 2001;13(6):1261 Sodium channels (NaChs) regulate neuronal excitability in both physiologic and pathological conditions, including epilepsy, and are therefore an important target for antiepileptic drugs (AEDs). In the present study, we examined the distribution of messenger RNAs (mRNAs) encoding neonatal NaChs II and III α-isoforms in control rat hippocampus and after electrically induced status epilepticus (SE), with nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus. By contrast, increased expression of neonatal NaCh II and III mRNAs was observed 4 hours after the induction of SE in neurons of CA1–CA3 and the dentate granule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intensely, for up to 3 months, when rats display spontaneous seizures. Strong expression of neonatal NaCh α-isoforms was observed 1 week after SE in microglial cells, as confirmed by double labeling, combining ISH with immunocytochemistry for microglia markers. The increased expression of neonatal isoforms of the NaCh in both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function, and pharmacologic response to AEDs in the course of epileptogenesis. Sodium Currents in Isolated Rat Ca1 Pyramidal and Dentate Granule Neurones in the Post-Status Epilepticus Model of Epilepsy Ketelaars SOM, Gorter JA, van Vliet EA, Lopes da Silva FH, Wadman WJ Neuroscience 2001;105:109–120 Status epilepticus (SE) was induced in the rat by long-lasting electrical stimulation of the hippocampus. After a latent period of 1 week, spontaneous seizures increased in frequency and severity in the following weeks, finally culminating after 3 months in a chronic epileptic state. In these animals, we determined the properties of voltage-dependent sodium currents in short-term isolated CA1 pyramidal neurons and dentate granule (DG) cells by using the whole-cell voltage-clamp technique. The conductance of the fast transient sodium current was larger in SE rats (84 ± 7 nS vs 56 ± 6 nS) but related to a difference in cell size, so that the neurons had a similar specific sodium conductance (control, 7.8 ± 0.8 nS/pF; SE, 6.7 ± 0.8 nS/pF). Current activation and inactivation were characterized by a Boltzmann function. After SE, the voltage dependence of activation was shifted to more negative potentials (control, −45.1 ± 1.4 mV; SE, −51.5 ± 2.9 mV; P &lt; 0.05). In combination with a small shift in the voltage dependence of inactivation to more depolarized potentials (control, −68.8 ± 2.3 mV; SE, −66.3 ± 2.3 mV), it resulted in a window current that was much increased in the SE neurons (median, 64 pA in control; 217 pA in SE; P &lt; 0.05). The peak of this window current shifted to more hyperpolarized potentials (control, −44 mV; SE, −50 mV; P &lt; 0.05). No differences were found in the sodium currents analyzed in DG cells of control and SE animals. The changes observed in CA1 neurons after SE contribute to enhanced excitability, in particular, when membrane potential is near firing threshold. They can, at least partly, explain the lower threshold for epileptic activity in SE animals. The comparison of CA1 with DG neurons in the same rats demonstrates a differential response in the two cell types that participated in very similar seizure activity.

Sodium currents in isolated rat CA1 pyramidal and dentate granule neurones in the post-status epilepticus model of epilepsy

Status epilepticus (SE) was induced in the rat by long-lasting electrical stimulation of the hippocampus. After a latent period of 1 week, spontaneous seizures occurred which increased in frequency and severity in the following weeks, finally culminating after 3 months in a chronic epileptic state. In these animals we determined the properties of voltage-dependent sodium currents in acutely isolated CA1 pyramidal neurones and dentate granule cells using the whole-cell voltage-clamp technique. The conductance of the fast transient sodium current was larger in SE rats (84±7 nS versus 56±6 nS) but related to a difference in cell size so that the neurones had a similar specific sodium conductance (control: 7.8±0.8 nS/pF, SE: 6.7±0.8 nS/pF). Current activation and inactivation were characterised by a Boltzmann function. After SE the voltage dependence of activation was shifted to more negative potentials (control: −45.1±1.4 mV, SE: −51.5±2.9 mV, P<0.05). In combination with a small shift in the voltage dependence of inactivation to more depolarised potentials (control: −68.8±2.3 mV, SE: −66.3±2.3 mV), it resulted in a window current that was much increased in the SE neurones (median: 64 pA in control, 217 pA in SE, P<0.05). The peak of this window current shifted to more hyperpolarised potentials (control: −44 mV, SE: −50 mV, P<0.05). No differences were found in the sodium currents analysed in dentate granule cells of control and SE animals. The changes observed in CA1 neurones after SE contribute to enhanced excitability in particular when membrane potential is near firing threshold. They can, at least partly, explain the lower threshold for epileptic activity in SE animals. The comparison of CA1 with DG neurones in the same rats demonstrates a differential response in the two cell types that participated in very similar seizure activity.

Pattern of nonadrenergic, noncholinergic responses during short- or long-lasting electrical stimulation in guinea-pig ileum

1. 1. The pattern of responses of longitudinally oriented guinea pig ileum organ bath preparations was studied during short- (1–5 sec) or long-lasting (20 sec) electrical field stimulation (EFS, 0.8 msec, 40 V, 1–20 Hz). 2. 2. In the presence of phentolamine (5 μM), propranolol (5 μM), and atropine (3 μM), the EFS elicited nonadrenergic, noncholinergic (NANC), tetrodotoxin (0.3 μM)-sensitive responses. 3. 3. The 1-sec EFS evoked relaxation. The response to 5-sec EFS consisted of relaxation followed by twitch, whereas relaxation, twitch and tonic contraction characterized the NANC response to 20-sec EFS. The maximum relaxation was observed at 10-Hz short- or long-lasting EFS. 4. 4. Both N-G-nitro- l-arginine ( l-NNA, 0.1-0.5 mM) and apamin (1–5 μM) concentration dependently inhibited the relaxation of the NANC response to 10-Hz 20-sec EFS. During L-NNA treatment, the twitch and the tonic contractions were increased. The inhibitory effect of L-NNA was reversed by L-arginine (0.1-0.5 mM) but not by D-arginine. Sodium nitroprusside (1–10 μM) was without effect. 5. 5. AP 13.2 ACOH (0.1 μM), a blocker of Substance P receptors, inhibited the twitch and the tonic contractions. The contractions were decreased after desensitization of purinoceptors by ATP and in the presence of the GABA A receptor antagonist bicuculline (30 μM). 6. 6. Depending on the EFS duration, a subsequent occurrence of relaxation and contractions characterized the NANC responses. It seems that relaxation is mediated by nitric oxide whereas Substance P and ATP are involved in the maintenance of the twitch and the tonic contractions. Nitric oxide appears to exert an inhibitory effect on the excitatory transmitters, whereas purinergic mechanism(s) could modulate the nitric oxide-dependent relaxation.

Neuropeptide Y in salivary glands of the rat: origin, release and secretory effects

In the parotid gland, double immunostaining showed the perivascular and most of the periductal neuropeptide Y (NPY)-immunoreactive nerve fibres to contain dopamine β-hydroxylase, while the majority of periacinar NPY-fibres contained vasoactive intestinal peptide. Sympathectomy caused a marked depletion of perivascular and periductal NPY-fibres, leaving periacinar NPY-fibres less affected. Following combined sympathectomy and parasympathectomy, only a few NPY-fibres persisted. The parasympathetic auriculo-temporal nerve contributed most (75%) and the cervical sympathetic nerve least (15%) to the parotid gland content of NPY as judged by radioimmunoassay. The sensory neurotoxin capsaicin was without effect on the occurrence and gland content of NPY. Upon long-lasting electrical stimulation of the auriculo-temporal nerve at a high frequency, the gland content of NPY was reduced (by 55%), a depletion thought to indicate release of the peptide from parasympathetic nerve terminals. In vitro, tissues of parotid, submandibular and sublingual glands released concentration-dependently protein (and as to the parotid gland amylase also) in response to NPY; the protein response was largest from sublingual tissue (per unit weight). A concentration-dependent in vitro release of potassium from tissues of parotid and submandibular glands in response to NPY occurred and here, submandibular gland tissue was the most sensitive. Comparisons between the action of some secretagogues (at 10 −6 M) showed NPY to be less effective than vasoactive intestinal peptide and adrenaline, but as effective as bethanechol and substance P, in releasing protein (and amylase) in parotid and submandibular gland tissues; in sublingual gland tissue NPY was less effective than vasoactive intestinal peptide, in the range of adrenaline and more effective than bethanechol and substance P. As to potassium release (at agonist concentration of 10 −6 M) from tissues of parotid and submandibular glands NPY was less effective than substance P and vasoactive intestinal peptide. The fluid response to NPY upon i.v. administration was scanty from parotid and submandibular glands. NPY is likely to play a complementary role in mediating parasympathetic secretory responses in salivary glands of the rat. It seems preferentially involved in the control of protein secretion.

Electrical stimulation of the Gasserian ganglion induces structural alterations of calcitonin gene-related peptide-immunoreactive perivascular sensory nerve terminals in the rat cerebral dura mater: a possible model of migraine headache

Calcitonin gene-related peptide (CGRP)- positive sensory nerve fibers in the rat supratentorial cerebral dura mater are equipped with varicosities and club-like nerve terminals, often attached to the walls of blood vessels. Brief electrical stimulation of the Gasserian ganglion results in significant swelling and increased immunohistochemical staining of ipsilateral perivascular club-like terminals, while long-lasting electrical stimulation induces their disintegration or bursting, resulting in irregular, corroded outlines of terminals and en passant beads. Stimulation-induced morphological alterations of perivascular terminals may represent a structural basis of increased CGRP content in jugular blood which follows electrical stimulation of the Gasserian ganglion and accompanies migraine attacks.

Calcitonin gene-related peptide in rat salivary glands: Neuronal localization, depletion upon nerve stimulation and effects on salivation in relation to substance P

Calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres occurred predominantly around blood vessels and large ducts and, to a minor extent, around acini and small ducts in the parotid, sublingual and submaxillary glands of the rat. Double immunostaining showed most of the CGRP-containing nerve fibres to contain substance P. However, the vast majority of substance P-immunoreactive periacinar nerve fibres in the parotid and submandibular glands lacked CORP. After parasympathetic denervation of the parotid gland by section of the auriculotemporal nerve these periacinar substance P-immunoreactive nerve fibres disappeared almost completely, whereas the number of substance P/CGRP-immunoreactive nerve fibres seemed unchanged. After this operation the total amount of substance P in the parotid gland was reduced by about 90% as judged by radioimmunoassay; in denervation experiments the facial nerve was found to contribute to the residual substance P content. In contrast, the contribution of the auriculotemporal nerve to the CGRP content of the gland was small; the reduction in CGRP after section of the nerve was 20%. The facial nerve and the dorsal root nerves (C3 and C4) contributed to the CGRP content with about 50%. The source of the remaining 30% of the parotid gland CGRP is unknown. It is not the sympathetic nerve: sympathetic denervation resulted in a marked increase in CGRP, regardless of whether the auriculotemporal nerve was intact or not. Upon long-lasting electrical stimulation of the auriculotemporal nerve at a high frequency the parotid gland content of CGRP was gradually reduced, indicating depletion of this peptide in response to nerve stimulation. Intravenous injections of CGRP evoked no salivary flow; however, a release of amylase was revealed. Also, when CGRP was tested on isolated parotid gland lobules amylase was released into the medium. When, in vivo, CGRP was injected in combination with substance P, the substance P-evoked flow of parotid and submaxillary saliva was markedly enhanced. In addition, CGRP enhanced the in vivo secretory response to parasympathomimetics and to vasoactive intestinal peptide. The localization of CGRP-containing nerve fibres suggests that CGRP is involved in the regulation of secretion and blood flow of salivary glands. CGRP may interact positively with acetylcholine and certain nonclassical transmitters and it may be involved (together with other neuropeptides) in the atropine-resistant parasympathetic secretion occurring in the glands under study.

Pharmacological characteristics of the postsynaptically mediated contractile responses of guinea-pig ileum to long-lasting electrical field stimulation

The contractile responses of the longitudinal smooth muscle layer of the isolated guinea-pig ileum which were elicited by long-lasting (40 sec train duration) electrical field stimulation (0.8 msec, 20 V), applied at a frequency of either 5 or 30 Hz, comprised an initial phasic component followed by a secondary tonic contraction, were studied against the background of postsynaptically-acting receptor antagonists. Atropine and apamin reduced both components of the responses while prazosin produced no change. Propranolol induced a slight reduction, decreasing mainly the responses evoked by stimulation at a frequency of 5 Hz. The simultaneous application of cholinoceptor and adrenoceptor Mockers revealed a non-cholinergic, non-adrenergic component of the responses. The putative prostaglandin antagonist, SC 19220 was found to reduce mainly the tonic component of the non-cholinergic, non-adrenergic contractions evoked by stimulation at both frequencies used. These results demonstrated that the two-component contractile responses of the guinea pig ileum to long-lasting electrical stimulation were due to the release of more than one neurotransmitter and/or spasmogenic substance. It is concluded that the initial phasic component was evoked by acetylcholine and by a non-cholinergic, non-adrenergic neurotransmitter, while the tonic component was maintained predominantly by prostaglandins released during stimulation.

Reduction of the monoamine stores in the terminals of bulbospinal neurones following stimulation in the medulla oblongata

Long-lasting electrical stimulation in the medulla oblongata of anaesthetized rats caused a marked reduction of the NA and 5-HT stores of varicose nerve terminals in the spinal cord as analyzed by histochemical and biochemical (for NA) methods.