Changes In Compound Action Potential Research Articles

Modulation of sensory input to the spinal cord: Contribution of focal epidural polarization and of GABA released by interneurons and glial cells.

Modulation of input from primary afferent fibres has long been examined at the level of the first relays of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated at the level of the very entry of afferent fibres to the spinal grey matter before action potentials in intraspinal collaterals of afferent fibres reach their target neurons. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only GABAergic interneurons but also glial cells. We present evidence, primo, that GABA released from both these sources contributes to a long-lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferent fibres and, secondo, that effects of epidural polarization on the release of GABA are more critical for these changes than direct effects of DC on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions.

Electrocochleography in Round Window Vibrant Soundbridge Implantation

To determine the role of intraoperative electrocochleography to optimize the fitting of the floating mass transducer of the Vibrant Soundbridge on the round window membrane in patients with conductive and mixed hearing loss. Prospective cohort study. Tertiary referral center, Otolaryngology Department, University of Verona, Verona, Italy. Twenty-six adult patients suffering from chronic otitis media with moderate to severe conductive and mixed hearing loss, all with previous unsuccessful functional surgery, underwent round window vibroplasty. Thirteen subjects had intraoperative compound cochlear action potentials measured to assess vibroplasty coupling during and after surgery. In these patients, surgery was modified according to electrocochleographic feedback. The other 13 had vibroplasty without electrocochleography monitoring. The average preoperative air conduction and bone conduction thresholds (0.5-4 kHz) were not statistically significantly different between the 2 cohorts (P > .05). Compound action potential recordings indicated specific surgical modalities to optimize coupling of the floating mass transducer with the round window membrane. The average postoperative Vibrant Soundbridge-aided air conduction threshold improvements (0.5-4 kHz) were 54.6 ± 8.9 and 41.7 ± 11.1 dB HL, respectively, in the monitored and unmonitored cohorts (P = .0032). Improved round window vibroplasty outcomes are observed when the surgeon is promptly informed of the compound action potential changes induced by the floating mass transducer round window membrane vibroplasty and alters surgery accordingly. The key point for optimal coupling is a floating mass transducer in full contact with the round window membrane, free to vibrate without any contact with the surrounding bony structures and mobile footplate.

Effects of a Nitric Oxide Synthase Type II Inhibitor on Compound Action Potential Thresholds in Experimental Endolymphatic Hydrops

Nitric oxide (NO) is likely to be synthesized by nitric oxide synthase Type II (NOS II) action and may partake in the origin of changes of compound action potential (CAP) threshold observed in guinea pigs with induced endolymphatic hydrops. This study aimed to assess the action of a NOS II inhibitor on CAP thresholds in these experimental samples. In guinea pigs with experimental endolymphatic hydrops, there are lesions on the cochlea and progressive increase of CAP threshold. NOS II was found in the cochlea of this animal model, and it was inferred that NO can contribute by such alterations. The animals were divided into two groups, in which eight received an intake of a NOS II inhibitor, aminoguanidine, and another eight served as a control group. During 16 weeks, CAP thresholds at 1,000, 2,000, 4,000 and 6,000 on electrocochleography were compared between the groups. The group that had an intake of aminoguanidine showed a lower increase on CAP thresholds at 2,000 (p < 0.05) and 6,000 Hz (p < 0.05) at the 12th postoperative week, and at 1,000 (p < 0.05), 2,000 (p < 0.001), 4,000 (p < 0.001), > and 6,000 Hz (p < 0.001) at the 16th week. We conclude that NOS II inhibitor reduced the elevation of CAP thresholds in experimentally induced endolymphatic hydrops.

Functional evidence for P2X receptors in isolated human vagus nerve.

Functional evidence for P2X receptors in isolated human vagus nerve.

Sensitivity of sensory axons to lidocaine nerve block in rats.

The aim of the present study was to test the sensitivity of different classes of sensory axons to lidocaine 2 and 4% nerve block. The basic approach was to examine changes in compound action potential (CAP) of A and C axons of the rat sural nerve induced by 2 or 4% lidocaine nerve block in vitro. CAP in control sural nerves (n = 6 for each experimental group) before nerve block was induced, consisted of the early component (A axons: 0.3 +/- 0.02 ms) and the late component (C axons: 12.2 +/- 1.14 ms) with peak voltage amplitudes 4.4 +/- 1.4 mV and 0.04 +/- 0.02 mV, respectively. Lidocaine 2% nerve block completely abolished the amplitude of CAP of C axons and depressed the amplitude of CAP of A axons to about 20 % of control level. Doubled concentration of lidocaine significantly decreased time taken to develop maximal depression of CAP and significantly increased excitation threshold of sensory A axons, but not of sensory C axons. However, 4% lidocaine did not affect the maximal depression of CAP of sensory A axons. These results support the view, that C axons are more sensitive to lidocaine nerve block than A axons. In addition, our results suggest a population of sensory A axons which is non-sensitive to 2% and 4% lidocaine.

Recovery from adaptation in human compound action potential following forward masking

Recovery from adaptation was studied as changes in compound action potential (CAP) in response to clicks after broadband noise masking in volunteers with normal hearing. CAP was transtympanically elicited from the promontory using a needle electrode. Preceding masking noise and subsequent click stimuli were delivered separately from 2 loud speakers 80 cm from the tested ear. We evaluated the effect of masking noise duration and intensity on CAP recovery from adaptation as a function of delta t, defined as the interval between masking noise offset and click stimulus onset. Results were as follows: At delta t shorter than 200 ms or less, recovery from latency prolongation and amplitude decrease slowed with increasing masking noise duration and intensity. At delta t longer than 200 ms, no significant difference was seen in CAP recovery based on changes in masking noise duration or intensity. Recovery from adaptation, which depended on click intensity, took about 700 ms at a 40 dBnHL click and about 300 ms at a 60 dBnHL click. The influence of the middle ear muscle reflex on CAP recovery patterns is neglected when considering the intensity both masking noise and click stimulus. In CAP recovery, accumulated effects of the relative auditory-nerve refractory period may adversely affect recovery at very short delta t, while recovery from short-term adaptation, assumed involved in cochlear-hair cell synapse function, may be an important factor at delta t longer than 30-40 ms. Based on animal experiments showing different recovery times dependent on different auditory nerve spontaneous rates(SR), we concluded that at delta t of 200 ms or less, CAP recovery reflects high SR neuron activity, while at delta t longer than 200 ms, it mainly reflects that of low SR neurons.

Sensitivity of peripheral nerve fibres to sodium pentobarbital anaesthesia in rat.

The sensitivity of different classes of peripheral nerve fibres to anaesthesia with sodium pentobarbital in rat was tested. The basic approach was to examine changes in compound action potential (CAP) in a rat sural nerve induced by sodium pentobarbital. Rats were either sacrificed by cervical dislocation (control) or anaesthetized with sodium pentobarbital (100 mg/kg, i.p.), and a 30 mm long sural nerve segment excised and placed on electrodes in a thermostatically controlled recording chamber. CAPs were evoked by electrically stimulating the sural nerve segment with supra-threshold stimuli. CAP in control sural nerves consisted of the early component (A axons: 32.73 ± 2.91 m/s) and the late component (C axons: 0.92 ± 0.05 m/s) with peak voltage amplitudes 4.9 ± 1.0 mV and 0.1 ± 0.03 mV, respectively. Anaesthesia with sodium pentobarbital had no effect on CAP latency. However, the amplitude of CAP of both A and C axons was reduced by approximately 40 % and 50 %, respectively. The depressant effect of pentobarbital on CAPs was statistically significant for both groups of axons (p<0.01). Non-selective sensitivity of A and C axons to pentobarbital suggests even distribution of receptors for GABA in these two populations of axons in the rat peripheral nerve.

Do click-evoked otoacoustic emissions have frequency specificity?

Whether click-evoked otoacoustic emissions (CEOAEs) have frequency specificity is an issue still subject to debate. In order to resolve this issue, changes in the frequency components of the CEOAE power spectrum, together with changes in compound action potential (CAP) thresholds before and after pure-tone exposure in guinea pigs, were examined. Changes in CAP thresholds immediately before and 1 h after exposure were compared with changes in the frequency components in the CEOAE power spectrum before and 1 h after exposure. The ILO 88 was used for measurement of CEOAEs. Total echo energy in the CEOAE power spectrum was converted into frequency bands of 1000 Hz. Shifts in filtered echo power (FEP) levels correlated maximally with those in CAP thresholds at 0.5 kHz above the same frequency. Stepwise regression indicated that only one step could be entered in a linear regression model using the variable of CAP threshold shifts at 0.5 kHz above the same frequency for all FEP shifts except FEP4.5. The remaining variables played a negligible role, since variance no longer changed when they were included in the regression equation. From these results, it was concluded that CEOAEs display frequency specificity. Influence on CEOAEs from higher frequencies is negligible.

Effect of cortisporin otic suspension on cochlear function and efferent activity in the guinea pig.

To predict cochlear receptor cell insult from therapeutic aminoglycoside antibiotics, we sought to determine whether the presence of subtoxic concentrations of Cortisporin otic suspension in the cochlea can be detected by measuring changes in efferent suppression of compound action potentials recorded from the round window. Olivocochlear efferent suppression in an earlier study was reversibly inhibited by injections of gentamicin in guinea pigs. Using that same technique, we found that 2.0 microliter of Cortisporin otic suspension (neomycin, polymyxin B, hydrocortisone) placed on the round window of guinea pigs in varying concentrations causes a rapid, permanent alteration in thresholds. Solutions of Cortisporin otic suspension diluted to a concentration of 1:20 yield a reversible loss of efferent suppression without measurable changes in compound action potential. These data suggest that the presence of Cortisporin otic suspension can be detected functionally in the cochlea at very low concentrations prior to the development of a threshold shift.

Improvement in Auditory Function Following Pentazocine Suggests a Role for Dynorphins in Auditory Sensitivity

The pharmacologic specificity of potentially beneficial drug effects on the auditory system were investigated. Changes in auditory sensitivity were evaluated in chinchillas following the infusion of an opioid narcotic. This drug (pentazocine) mimics endogenous opioid peptides (dynorphins), postulated to be chemical neurotransmitters (or neuromodulators) within the mammalian cochlea. In this study, two pentazocine enantiomers were investigated over a range of stimulus intensities. Significant baseline-relative changes in compound action potential (CAP) amplitudes were observed following intravenous administration of the kappa-opioid agonist (-)pentazocine (8 mg/kg). The sigma-receptor drug agonist (+)pentazocine (8 mg/kg) produced no measurable auditory effects. The magnitude of the (-)pentazocine effects were inversely related to stimulus intensity, up to 10 dB above threshold (i.e., 10 dB SL). Consistent with the observed amplitude doubling, auditory sensitivity was also improved an average 5-7 dB sound pressure level (SPL) following the administration of (-)pentazocine, while CAP response latencies and cochlear microphonic (CM) amplitudes remained unchanged. Results indicate stereospecific kappa-receptor mediated actions of pentazocine at the auditory nerve, and suggest an auditory role for neuroactive dynorphin peptides contained within the lateral efferent olivocochlear neurons.

Application of a neuroprotective ACTH(4-9) analog to affect cisplatin ototoxicity: an electrocochleographic study in guinea pigs.

Ototoxicity and neurotoxicity are among the most serious side-effects of cisplatin therapy. Previous experiments have shown that neurotoxicity can be delayed or prevented by treatment with the melanocortin-derived peptide ORG 2766, and ACTH4-9 analog. A remedy against ototoxicity is not available. In this study we describe cisplatin-induced abnormalities in cochlear potentials in guinea pigs. These included changes in compound action potential (CAP), cochlear microphonics (CM) and summating potential (SP) at frequencies from 500 Hz to 16 kHz. Cisplatin (2 mg/kg for 8 days) reduced CAP amplitude with the effect becoming more pronounced at higher frequencies. Cisplatin also reduced CM and SP. Concurrent treatment with ORG 2766 prevented cisplatin ototoxicity partially or completely in four out of ten animals. In the other six animals the effects were comparable to those seen in control animals not treated with the peptide. The protective effects found with this neurotrophic peptide warrant further experimentation.

Acute Progesterone Treatment Has No Effect on Bupivacaine-Induced Conduction Blockade in the Isolated Rabbit Vagus Nerve

Pregnancy decreases anesthetic requirements during regional anesthesia. Using an in vitro animal model, this study attempts to elucidate the mechanism of hormonal effects on nerve conduction in desheathed rabbit vagus nerve. The acute effects of progesterone administration on neural blockade induced by bupivacaine were investigated in terms of changes in compound action potentials of A, B, and C fibers. No change in baseline compound action potential was found after 30 min of perfusion of the nerve with progesterone. Exposure of the nerve to progesterone before exposure to bupivacaine did not significantly increase the degree of conduction blockade produced by bupivacaine, and a radioactive assay demonstrated that progesterone was taken up acutely by neural tissue over a 45-min measurement period. These results indicate that although progesterone was taken up in significant amounts by neural tissue, an acute exposure does not increase the sensitivity of the nerves to bupivacaine. Hence, the increased sensitivity of nerves to local anesthetics seen with pregnancy or with chronic progesterone treatment requires some period of time to occur. The mechanism is therefore unlikely to be a direct effect of progesterone on the cell membrane but may involve hormonal effects on protein synthesis.

The effects of temperature on human compound action potentials.

The upper limbs of 10 healthy subjects were cooled and then warmed over physiological temperature ranges. The compound action potentials of median digital nerves, median sensory nerve at the wrist, radial sensory nerve at the wrist, and median thenar muscle, all showed progressive reduction in latency, amplitude, duration and area during rising temperature. Our studies suggest that the sensory compound action potential changes occur predominantly because of the summated effects of reduction in the duration of the action potentials of single myelinated fibres, although disproportionate increase in the conduction velocity of larger myelinated fibres also plays a role.