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Chronic electrical stimulation of the auditory nerve using non-charge-balanced stimuli.

This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1 microA. Four normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods up to 2200 h. Stimuli consisted of 50 micros monophasic current pulses presented at 2000 pulses per second (pps) per channel, and resulted in DC levels of 0.4-2.8 microA. Both acoustic and electrical (EABR) evoked potentials were periodically recorded during the stimulation program. Frequency-specific stimuli indicated that an extensive and widespread hearing loss occurred over the 4-24 KHz region in all stimulated cochleae, although the 2 KHz region exhibited thresholds close to normal in some animals, despite long-term implantation and chronic stimulation. Longitudinal EABRs showed a statistically significant increase in threshold for three of the four animals. Histopathological evaluation of the cochleae revealed a highly significant reduction in ganglion cell density in stimulated cochleae compared with their controls. Spiral ganglion cell loss was significantly correlated with the degree of inflammation, duration of electrical stimulation, and the level of DC. In conclusion, the present study highlights the potential for neural damage following stimulation using poorly charge-balanced stimuli.

Action Potentials↗

Input-output organization in the hand area of the human motor cortex.

The primate motor cortex consists of efferent zones which receive sensory information from a portion of limb in close anatomical relation to the muscle to which they project. To investigate a similar input-output relation in humans, we studied the effect of tactile stimuli on the size of motor evoked potentials (MEPs) elicited by transcranial magnetic and electrical stimulation. For tactile stimuli we applied air to the skin. The sizes of MEP of 3 finger muscles (flexor pollicis brevis, first dorsal interosseous, and abductor digiti minimi) with and without air stimuli were compared. Air stimuli applied to the tip of one finger facilitated mainly the magnetically evoked MEP of a muscle attached to that finger. A less obvious facilitatory effect was observed when giving stimuli on the dorsal aspect of the hand. Air stimuli had no facilitatory effect on electrically evoked MEPs. In one subject, there was no facilitatory effect even to magnetically evoked MEPs. In this subject, D-waves had the lowest threshold for magnetic and electrical stimulation. These results suggested that the effect was produced at the cortical level. This effect may correspond to the input-output relation found in the primate motor cortex.

Electric Stimulation↗

A personal computer-based visual evoked potential stimulus and recording system.

A system for recording electroretinograms and visual evoked cortical potentials has been constructed with the use of a personal computer and a digital signal processing card. The system is based on widely available commercial hardware. It has been designed to be capable of performing routine visual electrophysiology as well as allowing the development of novel visual stimuli and signal detection techniques. The system enables both transient and steady-state stimulation rates. Pattern stimuli can be presented in pattern-reversal, pattern-onset, pattern-offset or motion-onset modes. In addition to conventional signal averaging, the digital signal processing card can also provide on-line Fourier analysis and is facilitating the development of adaptive filtering techniques for the detection of steady-state visual evoked cortical potentials. This versatile system is in regular clinical use for the measurement of electroretinograms and visual evoked cortical potentials.

Electrophysiology↗

Somatosensory cortex: a comparison of the response to noxious thermal, mechanical, and electrical stimuli using functional magnetic resonance imaging.

In the present study, functional magnetic resonance imaging (fMRI) was used to examine pain perception in humans. Three types of noxious stimuli were presented: electric shock (20.8 mA, 2 Hz), heat (48 degrees C), and mechanical, as well as a control tactile stimulus. The significance of activation at the level of the voxel was determined using correlation analysis. Significant region of interest (ROI) activation was determined by comparing the percentage of active voxels in each ROI to activation in a control ROI in the visual cortex. In response to tactile and shock stimuli, consistent activation was seen in the postcentral gyrus, parietal operculum, and ipsilateral cerebellar cortex. No significant cortical activation was detected in response to noxious heat or mechanical stimulation when compared to nonpainful intensity levels. The data did not indicate adaptation, although further study in this area is necessary. Stationary noxious thermal and mechanical stimulation are "pure" noxious stimuli, while electrical stimulation influenced nociceptive and nonnociceptive receptors. Lack of detectable activation in response to pure noxious stimuli supports the idea that nociceptive and nonnociceptive fibers are interspersed in the somatosensory cortex. Conflicting results from recent functional imaging studies of pain perception regarding cortical activation indicate that it is essential to consider both the tactile and nociceptive components of the stimuli used, the spatial extent of stimulation, and the possibility of adaptation to the response. Furthermore, these results suggest that subtractive or correlative methods may not be sufficiently sensitive to image the activity of nociceptive cells, which are sparsely distributed throughout the somatosensory cortex.

Adolescent↗

Responses of single cells in cat visual cortex to prolonged stimulus movement: neural correlates of visual aftereffects.

1. The activity of single cortical cells in area 17 of anesthetized and unanesthetized cats was recorded in response to prolonged stimulation with moving stimuli. 2. Under the appropriate conditions, all cells observed showed a progressive response decrement during the stimulation period, regardless of cell classification, i.e., simple, complex, or hypercomplex. 3. The observed response decrement was shown to be largely cortical in origin and could be adequately described with an exponential function of the form R = Rf +(R1-Rf)e-t/T. Time constants derived from such calculations yielded values ranging from 1.92 to 12.45 s under conditions of optimal-stimulation. 4. Most cells showed poststimulation effects, usually a brief period of reduced responsiveness that recovered exponentially. Recovery was essentially complete in about 5-35 s. 5. The degree to which stimuli were effective at inducing response was shown to have significant effects on the magnitude of the response decrement. 6. Several cells showed neural patterns of response and recovery that suggested the operation of intracortical inhibitory mechanisms. 7. A simple two-process model that adequately describes the behavior of all the studied cells is presented. 8. Because the properties of the cells studied correlate well with human psychophysical measures of contour and movement adaptation and recovery, a causal relationship to similar neural mechanisms in humans is suggested.

Anesthesia, General↗

Interactions between perinatal and neonatal associative learning defined by contiguous olfactory and tactile stimulation.

Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre- and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.

Administration, Inhalation↗

Pocket Monster incident and low luminance visual stimuli: special reference to deep red flicker stimulation.

On the evening of 16 December 1997 approximately 700 people around the nation (mostly children) were rushed to hospitals and treated for seizure symptoms. The youngsters had been watching the vastly popular TV animated cartoon series Pocket Monsters (Pokemon). We designated those individuals as a main group, who presumably had simultaneous occurrence of visually induced seizures. Follow-up studies revealed that 5-10.4% of Pokemon viewers had various minor symptoms not requiring hospital treatment. We designated those as a subgroup. Due to an official report regarding the problematic TV scene as a low luminance, 12 Hz alternating red/blue stimulus, we attempted an accounting of the Pokemon incident, with regard to the main group in particular, on the basis of electroencephalographic activation by use of low luminance 15 Hz deep red flicker stimulation. In order to explain the entire Pokemon incident, including symptoms experienced by individuals of the subgroup, we considered the possibility that some healthy youngsters may have latent photosensitivity and we thought that such a sensitivity might be disclosed by use of low luminance deep red flicker stimulation which is more provocative of photoparoxysmal response than ordinary high luminance stroboscopic intermittent photic stimulation. For prevention of visually induced seizures by TV viewing, we stress that care should be taken to test not only red flicker but also flickering geometric pattern stimuli.

Cartoons as Topic↗

Transcranial magnetic stimulation to the parietal lobes reduces detection of contralateral somatosensory stimuli.

OBJECTIVES: Neglect has been described in patients with lesions of the parietal cortex and has been interpreted as a disorder of the allocation of spatial attention. The persistence of neglect has been linked to poor rehabilitation outcome in patients suffering from acute stroke. Transcranial magnetic stimulation (TMS) applied to the parietal cortex has been shown to induce changes in the perception of stimuli including tactile stimulation of the fingers contra- and ipsilateral to the stimulated hemisphere. MATERIAL AND METHODS: In the current study, eleven normal young subjects performed a detection task for cutaneous electrical stimuli to the left or right forearm that had been precued by a preceding visual warning stimulus. To investigate the role of the parietal cortical areas for attentional processes TMS was applied to frontal and parietal scalp sites of each hemisphere in the cue-target interval before the somatosensory stimulus. RESULTS: Right and left parietal stimulation led to reduced detection sensitivity for near threshold stimuli to the forearm contralateral to the stimulated hemisphere without hemispheric differences. Ipsilateral tactile perception was not influenced by parietal TMS and there was no change in perception after frontal stimulation to left or right scalp sites. CONCLUSION: This pattern of results is consistent with a role of the right and left parietal lobe in the distribution of spatial attention and provides an experimental basis for possible therapeutical application of TMS to improve attentional deficits in stroke patients.

Adult↗

Effects of continuous conditioning noise and light on the auditory- and visual-evoked potentials of the guinea pig.

Neurophysiological studies aiming to explore how the brain integrates information from different brain regions are increasing in the literature. The aim of the present study is to explore intramodal (binaural, binocular) and intermodal (audio-visual) interactions in the guinea pig brain through the observation of changes in evoked potentials by generalized continuous background activity. Seven chronically prepared animals were used in the study and the recordings were made as they were awake. Epidural electrodes were implanted to the skulls by using stereotaxic methods. Continuous light for retinal or continuous white noise for cochlear receptors were used as continuous conditioning stimuli for generalized stimulation. To evoke auditory or visual potentials, click or flash were used as transient imperative stimuli. The study data suggest that (a) white noise applied to one ear modifies the response to click in the contralateral ear which is a binaural interaction; (b) continuous light applied to one eye modifies the response to flash applied to the contralateral eye which is interpreted as a binocular interaction; (c) regardless of the application side, white noise similarly modified the response to flash applied to the either eye connoting a nonspecific effect of white noise on vision, independent from spatial hearing mechanisms; (d) on the other hand, continuous light, in either eye, did not affect the response to click applied to any ear, reminding a 'one-way' interaction that continuous aural stimulation affects visual response.

Acoustic Stimulation↗

Anterior pretectal nucleus facilitation of superficial dorsal horn neurones and modulation of deafferentation pain in the rat.

1. Functional relationships between the anterior pretectal nucleus (APTN) and nociceptive dorsal horn neurones were investigated electrophysiologically in the anaesthetized rat. The effects of APTN lesions were assessed behaviourally in a model of deafferentation pain. 2. Cells in the dorsal and rostral parts of the APTN were excited orthodromically by electrical stimulation of the ipsilateral dorsolateral funiculus or the contralateral dorsal columns, and by noxious and innocuous cutaneous stimuli. 3. Electrical stimulation of the APTN excited nociceptive lamina I spinal neurones. These cells all projected rostrally in the contralateral dorsolateral funiculus. Identical APTN stimulation also inhibited multireceptive spinal neurones which lay deep in the dorsal horn. These particular cells were shown to project to the brain in the ventrolateral funiculus. 4. It is proposed that noxious stimuli excite spinal lamina I projection neurones which send excitatory axons to the brain, including the APTN. The APTN inhibits deep multireceptive neurones, to reduce the perception of noxious stimuli. The discharge of spinal lamina I neurones, however, will be sustained by the noxious stimulus and by facilitation from the APTN. A sustained descending inhibition of this nature would reduce responses to prolonged injury. 5. The involvement of the APTN in responses to a chronic pain state was examined by comparing the behaviour of animals with bilateral lesions of the APTN with normal controls. Lesions of the APTN strongly enhanced the autotomy behaviour triggered by sectioning of the dorsal roots. 6. These observations support the suggestion that the APTN reduces the debilitating effects of prolonged injury.

Afferent Pathways↗

Illusory persistence of touch after right parietal damage: neural correlates of tactile awareness.

We studied a patient who experienced 'palinaesthesia', an illusion of persistent touch following tactile stimulation on the left hand, subsequent to a right parietal meningioma affecting primary somatosensory regions in the postcentral gyrus (SI) and superior parietal gyrus (Brodmann area 7), but preserving the secondary somatosensory cortex (SII) in the upper lateral sulcus. This subjective sensation was accompanied by transient increases in objective measures of tactile threshold. The patient had mild deficits in superficial tactile perception, but showed severe left-sided extinction for offsets of tactile stimuli during bilateral stimulation, but not for onsets of stimuli. Functional MRI revealed increased neural activity during palinaesthesia selectively arising within the ipsilesional-right SI cortex, but no abnormality within left SI and bilateral SII. Right SI responded to the onset of new tactile stimuli on the left hand but not to their offset. By contrast, any tactile events on either hand modulated activity in contralateral SII regions, even undetected left-sided offsets. These data demonstrate that illusory persistence of touch following stimulation on the hand may result from sustained neural activity in a restricted region of the SI cortex outlasting the offset of the actual tactile stimuli. These findings also provide direct evidence for a critical role of SI in mediating conscious somatosensory experience on contralateral parts of the body.

Aged↗

Monitoring of neuromuscular function.

Clinical monitoring of neuromuscular function can be accomplished by either measuring the evoked mechanical or EMG response of a skeletal muscle via an accessible motor nerve. The pattern of motor nerve stimulation varies from supramaximal single repeated stimuli at a specified frequency to tetanic stimulation, posttetanic single stimuli at the pretetanic frequency, and train-of-four stimuli at 2 Hz. The response to relaxants is unpredictable in the population at large and more so in pathologic states. This makes monitoring of the muscle response to motor nerve stimulation extremely valuable and helpful. The train-of-four technique of measurement has proved to be valuable not only as a reliable clinical tool to measure the response to relaxants and monitoring recovery, but also as a research tool for studies of old and new neuromuscular blocking drugs. Evoked responses and clinical criteria for adequate recovery from muscle relaxants should complement each other. The more criteria fulfilled, the better and safer the conclusion that the patient has recovered from clinical neuromuscular blockade.

Anesthesia Recovery Period↗

The interval-strength relationship in mammalian atrium: a calcium exchange model. I. Theory.

A model is developed for predicting the interval-strength relationship in mammalian atrium. The postulates underlying the model relate the intracellular and transmembrane calcium fluxes to changes in contractility. The predictions of the model agree qualitatively with the behavior of atrium for the following patterns of stimulation: (a) constant interval between stimuli, (b) a rest, or period with no stimuli, after the attainment of a steady-state force level, (c) a sudden change in the interval between stimuli, and (d) paired pulse stimulation. The effects of varying several parameters of the model on both the contraction staircases, after a rested-state contraction, and the steady-state interval-strength relationship are examined. Additional considerations are made: (a) estimates are made of the tissue calcium content available for contraction; (b) the physical meaning of the rested-state contraction is discussed; and (c) estimates are made of the proportionality constant between the maximum value of the contractile tension and the amount of calcium released before a contraction.

Action Potentials↗

Effects of hippocampal manipulations on the classically conditioned nictitating membrane response: simulations by an attentional-associative model.

The effects of various hippocampal manipulations on the classically conditioned nictitating membrane (NM) response were simulated by a real-time attentional-associative model. The model incorporates: (a) a mechanism capable of establishing associations between conditioned (CS) and unconditioned stimuli (US) and between two CSs, (b) a mechanism that combines CS-CS and CS-US associations and builds 'computational cognitive maps', (c) an attentional rule that 'tunes in' relevant CSs and 'tunes out' irrelevant CSs, (d) performance rules that convert learning variables into topography of the rabbit NM response, and (e) rules that convert learning variables into neuronal firing. The present study explored three hypotheses regarding hippocampal function: (a) hippocampal lesions (HL) impair the 'tuning out' of irrelevant stimuli, (b) hippocampal stimulation (HS) and hippocampal long-term potentiation (LTP) facilitate the 'tuning in' of relevant stimuli, and (c) hippocampal unit activity is proportional to the instantaneous value of associative variables that participate in the 'tuning' mechanisms. Computer simulations for the HL case were carried out for conditioning under different interstimulus intervals (ISI) with different types of US, discrimination reversal, and sensory preconditioning. Computer simulations for the HS and LTP case were carried out for acquisition of delay conditioning and of classical discrimination. In addition, simulations of hippocampal unit activity during acquisition and extinction are presented. Under the 'tuning out' hypothesis for the HL case, the model proved capable of simulating a large portion of the experimental data, showing discrepancies with relevant literature only when describing HL effects on trace conditioning with shock US under short and long ISIs, trace conditioning with air puff US under long ISIs, discrimination reversal and sensory preconditioning. Under the 'tuning in' hypothesis regarding the HS and LTP case, the model proved capable of simulating acquisition of delay conditioning but not acquisition of classical discrimination. Under the assumption that neuronal activity is proportional to the instantaneous value of associative variables, the model is able to simulate hippocampal unit activity.

Animals↗

Neuronal responses in cat primary auditory cortex to electrical cochlear stimulation. II. Repetition rate coding.

1. Responses of neurons in primary auditory cortex (AI) of the barbiturate-anesthetized adult cat were studied using cochlear stimulation with electrical and acoustic stimuli. Neuronal responses to acoustic stimulation with brief biphasic clicks of the ear ipsilateral to the studied cortical hemisphere were compared with those evoked by electrical stimulation of the contralateral cochlea with brief biphasic electrical pulses delivered via a feline cochlear prosthesis. The contralateral ear was deafened immediately before implantation of the cochlear prosthesis. The feline cochlear prosthesis consisted of four bipolar electrode pairs and was placed in the scala tympani. Two bipolar electrode conditions were used for stimulation: one near radial pair with electrode spacing of 0.25-0.5 mm, and one longitudinal pair with electrode spacing of approximately 6 mm. 2. The firing rates obtained from single- and multiple-neuron recordings were measured as a function of stimulus repetition rate of electrical and acoustic pulses. From period histograms over a recording interval of 1,000 ms, the driven firing rate to repetition rates from 2 to 38 Hz was obtained and repetition rate transfer functions (RRTFs) were constructed. The RRTFs were characterized as low-pass or band-pass filters and several descriptors were obtained, such as the repetition rate producing the highest driven activity, high and low cutoff frequencies 6 dB below maximum firing rate, and maximum firing rate. 3. For a given neuron, the main characteristics of cortical RRTFs obtained with electrical and acoustic cochlear stimulation were quite similar. However, some small but statistically significant differences in the best repetition rate, cutoff frequencies, and maximum firing rate could be observed between the different stimulation modes. The proportion of band-pass RRTFs was larger for electrical stimulation (57%) than for acoustic stimulation (41%). The high cutoff frequencies for electrical stimulation were slightly but consistently higher than for acoustic RRTFs of the same neuron and the maximum firing rate for electrical stimulation was significantly higher than that evoked by ipsilateral acoustic stimulation. 4. The entrainment of cortical neurons to electrical and acoustic pulses was determined and entrainment profiles were constructed. For a given neuron, electrical entrainment profiles showed higher cutoff frequencies than with acoustic stimulation when judged with a fixed entrainment criterion of 0.25 spikes per event. The maximum entrainment seen for electrical stimulation was approximately 20% higher than seen for the same neuron with acoustic stimulation. 5. Correlation analysis of repetition coding and latency parameters revealed several relationships between these response aspects. Most prominent among them was a significant correlation between measures of the response latency and estimates of the ability to follow temporal repetitions for acoustic as well as electrical conditions. 6. Parametric and comparative evaluations of cortical responses to acoustic and electrical cochlear stimulation support the conclusion that the temporal resolution seen in cortical neurons is largely a consequence of central processing mechanisms based on cell and circuit properties and to a lesser degree a consequence of particular spatial and temporal peripheral excitation patterns. The slightly higher temporal resolution found for the electrical stimulation modes suggests that the temporally highly coherent electrical stimulation appears to engage, in a more effective manner, the excitatory/inhibitory mechanisms contributing to the response in AI than acoustic click stimulation with less temporal coherence. (ABSTRACT TRUNCATED)

Acoustic Stimulation↗

Effect of a serotonergic extrinsic modulatory neuron (MCC) on radula mechanoafferent function in Aplysia.

The serotonergic metacerebral cells (MCCs) and homologous neurons in related mollusks have been extensively investigated within the context of feeding. Although previous work has indicated that the MCCs exert widespread actions, MCC modulation of sensory neurons has not been identified. We characterized interactions between the MCCs and a cell that is part of a recently described group of buccal radula mechanoafferents. The cell, B21, has a peripheral process in the tissue underlying the chitinous radula [the subradula tissue (SRT)]. Previous studies have shown that B21 can fire phasically during ingestive motor programs and provide excitatory drive to the circuitry active during radula closing/retraction. We now show that activity of B21 can be modulated by serotonin (5-HT) and the MCCs. Centrally, although a slow depolarization is typically recorded in B21 as a result of MCC stimulation, this depolarization does not cause B21 to spike. It can, however, increase B21 excitability enabling a pulse that was previously subthreshold to elicit an action potential in B21. B21 is in fact rhythmically depolarized during the radula closing/retraction phase of ingestive motor programs. Thus central effects of the MCCs on radula mechanoafferent activity are only likely to be apparent while B21 is receiving input from the feeding central pattern generator. Peripherally, radula mechanoafferent neurons can be activated 1) when a mechanical stimulus is applied to the biting surface of the SRT and 2) when the SRT contracts. MCC stimulation and 5-HT modulate B21 responses to both types of stimuli. For example, MCC stimulation and low concentrations of 5-HT cause subthreshold mechanical stimuli applied to the SRT to become suprathreshold. 5-HT and MCC stimulation also enhance SRT contractility. Peripheral effects of MCC activity are also likely to be phase dependent. For example, MCC stimulation does not cause B21 to respond to peripheral stimuli with an afterdischarge. Consequently, radula mechanoafferents are likely to be activated when food is present between the radula halves during radula closing/retraction but are not likely to continue to fire as opening/protraction is initiated. In a similar vein, MCC effects on the contractility of the SRT will only be apparent when contractions are elicited by motor neuron activity. SRT motor neurons are rhythmically activated during ingestive motor programs. Thus we have shown that radula mechanoafferent activity can be modulated by the MCCs and that this modulation is likely to occur in a phase-dependent manner.

Animals↗

Immediate-early genes in the nervous system-are they involved in mechanisms of chronic pain?

Evidence suggests that long-term changes in the nervous system may represent a cause of chronic pain. Recent processes became accessible at the cellular level of the nervous system by analyzing immediate-early genes (IEG). The nuclear proteins encoded by these genes function as transcription factors, i.e. they control the expression of other genes. Many conditions of physiological and pathological stimulation can activate IEGs in the nervous system, and these findings have led to the concept of "stimulation-transcription-coupling". Noxious stimuli such as electrical C-fibre stimulation, noxious skin heating or subcutaneous formalin injection result in the transsynaptic induction of the IEG encoded proteins c-Fos, C-Jun and Krox-24, in the dorsal horn of the spinal cord. Non-noxious stimuli usually fail to induce the expression of IEGs. Nerve lesions result in a selective expression of C-Jun protein in the axotomized nerve cells, both in the peripheral and central nervous systems. Expression of IEGs after noxious stimuli and nerve lesions last for days or weeks, indicating profound alterations in the biochemistry and function of nerve cells. These changes could be involved in central nervous mechanisms of chronic pain.

Chronic Disease↗