Brief, prolonged and repeated stimuli applied to hyperalgesic skin areas: a psychophysical study

In this experimental study brief/prolonged and single/repeated, nociceptive stimuli (laser, thermode and electrical) were used to investigate sensory changes in capsaicin-induced primary and secondary hyperalgesia. The pain threshold to prolonged thermode stimulation was reduced in the primary area and remained constant in the secondary area. The pain thresholds to brief laser and electrical stimuli remained constant in the primary but reduced in the secondary area. The summation pain threshold to repeated (five stimuli delivered at 0.5, 1, 2 and 3 Hz) laser and electrical stimuli was reduced in the secondary area. The stimulus response functions to single laser and electrical stimuli were increased in the secondary area.     

Neuroethological studies of reflex plasticity in intact Aplysia..

Multi-unit recording of siphon nerve activity in intact Aplysia californica (a marine gastropod) with chronically implanted cuff electrodes provided a monitor of activity in a central pattern generator, the Interneuron II (Int II) network, which produces large siphon and gill contractions both spontaneously and after tactile stimulation of the siphon. The phase–response curve of the Int II oscillator for single stimuli at different phases of the cycle showed a "refractory" period early in the cycle, after which most stimuli phase advanced the oscillator and caused a short-latency Int II burst and a large contraction. The amplitude of gill withdrawal and the duration of siphon withdrawal in response to different stimulus intensities depended on whether an Int II burst was triggered. Activation of the Int II oscillator transformed the reflex from one that was graded smoothly with stimulus intensity to one in which nearly maximal responses were elicited even by weak stimuli. Entrainment and habituation training both involved monotonous repetition of a stimulus at specific intervals. With repeated siphon stimuli, nearly maximal reflex responses were maintained in intact Ss as long as the Int II oscillator was entrained, whereas habituation was associated primarily with failure to entrain the oscillator. Sensitized Ss showed significantly more triggered Int II burst than did controls. Digital spike-train analysis indicated that individual siphon motoneurons showed significantly increased background activity that often persisted for several minutes. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of multidrug resistance (mdr) gene(s) in primary lymphoid organs of chicken immune system during embryonic development

The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans.     

Mechanical response properties of nociceptors innervating feline hairy skin

1. The responses of feline cutaneous nociceptors were examined in vivo by systematically manipulating the intensive and spatial dimensions of mechanical stimulation. A computer-controlled motor was used to apply prescribed forces (5-90 g) to a nociceptor's receptive field, with flat-tipped, cylindrical probes of various sizes (contact areas: 0.1-5.0 mm2). The stimulating device and protocols were similar to those previously used to evaluate human perception, thus allowing for comparisons of the two data sets. 2. With a ramp-and-hold stimulus of controlled force, most nociceptors showed a slowly adapting (SA) response throughout the stimulus. In this way, nociceptors resembled low-threshold SA mechanoreceptors. However, in contrast to SA mechanoreceptors, nociceptors failed to exhibit an onset burst of activity associated with the stimulus ramp. Nineteen percent (6 of 31) of the nociceptors often showed the opposite trend during the stimulus, e.g., a gradually increasing firing rate. Most of these nociceptors (5 of 6) had particularly high mechanical thresholds. 3. With 30 stimuli repeated at short intervals (6-8 s), response rates tended to decrease across trials. This phenomenon was most evident with more intense stimuli. When two series of stimuli were separated by 4-5 min, there was no apparent trend of reduced responsiveness between series. 4. Overall, nociceptors responded in an orderly way to variations in force and probe size. For a given probe size, larger forces produced greater responses; for a given force, smaller probes produced greater responses. The relationship between probe size and force was best described as an even tradeoff between force and a linear dimension of the probe (i.e., probe perimeter), rather than the area of the probe. Thus a given pressure (force/area) did not evoke the same response from nociceptors as probe size was varied. 5. There were two significant differences in the mechanical responsiveness between A fiber and C fiber nociceptors. First, for a given set of stimuli, A fiber nociceptors exhibited a greater response rate than the C fiber nociceptors. Second, the A fiber nociceptors exhibited a greater differential response related to probe size than the C fiber nociceptors. On the basis of these two features, the A fiber nociceptors' response profiles showed a closer parallel with previously reported human pain thresholds than the C fiber nociceptors did. 6. When the nociceptors were subdivided as to their mechanical threshold, those with lower thresholds [mechanically sensitive afferents (MSAs)] showed a response saturation with the more intense stimuli. On average, the stimulus levels at which saturation occurred were close to human pain threshold. Those nociceptors with higher thresholds [mechanically insensitive afferents (MIAs)] did not show such saturation. Thus only the MIAs appeared to have the capacity to unambiguously encode mechanical stimulus intensities above pain threshold. The MSAs, on the other hand, exhibited their greatest dynamic response range near the threshold for nonpainful sharpness. Thus the group of afferents commonly defined as nociceptors exhibit a heterogeneity of mechanical response properties, which may serve functionally different roles for perception.     

Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities

BACKGROUND: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. METHODS: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. RESULTS: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. CONCLUSIONS: Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.     

The organ involvement and treatment in SLE

The motor effects of stimuli delivered through four-channel, quadripolar macroelectrodes chronically implanted in the ventrolateral thalamus were studied in 20 awake cooperating human subjects. Single stimuli could inhibit voluntary contraction of the contralateral first dorsal interosseous muscle (FDI) for up to 200 ms. The inhibition was often followed by a rebound facilitation or by oscillatory activity. This inhibition appeared to arise from the ventrolateral thalamus and could not be obtained in other patients by stimulation of the periventricular grey matter (PVG), the globus pallidus internus (GPI), or the subthalamic nucleus (STN). The neural elements activated by the stimulus had a short chronaxie and a short refractory period, implying that they were large-diameter axons. Similar effects were obtained from each of the four electrodes in the row, suggesting that this fiber system lay parallel rather than perpendicular to the implanted macroelectrode. The inhibition resulting from a single stimulus was diminished by a prior stimulus or train of stimuli. A continuous train of stimuli produced inhibition for only the first 200 ms. We propose that the thalamic stimulus activates a neural network which includes thalamic relay cells and neurons of the thalamic reticular nucleus and that the inhibition of thalamic relay cells habituates with repeated stimuli. It has been suggested that parkinsonian rest tremor results from synchronization of the oscillatory activity of this network. If this is the case, continuous thalamic stimulation might disrupt this oscillation by diminishing the inhibitory phase.     

Application of focused ultrasound for research on pain

Exteroceptive silent periods (ESPs) of masseter muscle activity evoked by electrical stimulation of the mental nerve were studied over a large range of prepain intensities and at pain threshold in 44 normal subjects. Seven levels of stimulus intensity, based on individual sensory and pain thresholds, were applied and the relationship between ESPs, stimulus intensity and perception, as manifested by the subjective verbal response, was investigated. The analysis revealed that the occurrence of ESPs was not related to the stimulus intensity at the pain threshold. There were individually different patterns of progressive response to increasing current intensities within the pre-pain range in many cases. On the other hand, almost half of all the subjects investigated showed no or only occasional ESPs. In view of this variability the concept of ESPs being a nociceptive behavioural response has to be questioned.     

Taking a bright view of negative priming in the light of dim stimuli: Further evidence for memory confusion during episodic retrieval.

A same–different letter-matching task was used to examine the effects of stimulus intensity on negative priming, which is poorer performance when target letters have been presented as distractor letters on the immediately preceding trial. In Exp 1, with 68 college students, stimulus intensity was manipulated between-participants, whereas in Exp 2, with 32 college students, it varied randomly from trial-to-trial within-participants. In Exp 1, negative priming was equivalent for both stimulus intensities. In Exp 2, negative priming effects were larger for repeated intensity stimuli than for nonrepeated intensity stimuli, when stimulus intensity was dim. Furthermore, for repeated intensity stimuli, negative priming effects were enhanced when the overt response required to the stimulus was repeated from prime to probe trial. These results are consistent with the hypothesis that negative priming may be due to memory confusion, rather than to inhibition of the distractor stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Responses of cutaneous A-fiber nociceptors to noxious cold

Responses of cutaneous nociceptors to natural stimuli, particularly mechanical and heat stimuli, have been well documented. Although nociceptors are excited by noxious cold stimuli, there have been few studies of their stimulus-response functions for cold stimuli over a wide range of stimulus temperatures. Furthermore, the proportion of nociceptors excited by noxious cold is not clear. In the present study, we examined responses of mechanosensitive A delta-nociceptors and low-threshold mechanoreceptors to a wide range of cold stimuli that included stimulus temperatures <0 degrees C. Electrophysiological recordings were made from single primary afferent fibers in the saphenous nerves of anesthetized rats. Cutaneous sensory receptors were classed according to their conduction velocity and subgrouped functionally according to their responses evoked by mechanical, heat, and cold stimuli (0 degrees C). Responses evoked by a wide range of cold stimulus intensities that included stimuli considered innocuous and noxious (painful) were then assessed. Stimuli of 20 to -20 degrees C were delivered to the receptive field via a 1-cm2 contact thermode from a base temperature of 32 degrees C. Stimuli were applied in descending order of 2 degrees C decrements. Stimulus ramp rate was 5 degrees C/s, and stimulus temperatures were applied for a duration of 10 s. A total of 90 A fibers was studied, of which 61 were nociceptors and had conduction velocity in the A delta-range (2-30 m/s). Nociceptors were classed initially as mechanical, mechanoheat, and mechanocold nociceptors. The remaining 29 fibers were low-threshold mechanoreceptors with conduction velocity in the A delta- or A beta-range (>30 m/s). These were subgrouped according to their adaptive properties as slowly or rapidly adapting, and according to whether they were excited by hair movement (hair follicle afferent fibers). All nociceptors were excited by noxious cold. Only 30% of nociceptors were considered sensitive to cold on initial classification with the use of a cold stimulus of 0 degrees C. However, all nociceptors were excited by stimulus intensities <0 degreesC. Response thresholds for cold ranged from 14 to -18 degrees C (-4.6 +/- 1.07 degrees C, mean +/- SE). The total number of impulses, discharge rate, and peak discharge increased monotonically as intensity of cold stimuli increased. Power functions were used to determine the rate at which the number of impulses increased as stimulus intensity increased. The slopes of power funcions ranged from 0.12 to 2.28 (mean 1.07 +/- 0.13). Most mechanoreceptors were not excited by cold stimuli. The only types of mechanoreceptors that responded reliably to cold stimuli were the slowly adapting mechanoreceptors. Responses usually occurred during the temperature ramp when the skin temperature was decreasing. There was no evidence that mechanoreceptors encoded the intensity of cold stimuli at intensities above or below 0 degrees C, because evoked responses did not increase with intensity of cold stimuli. It is concluded that the proportion of cutaneous A delta-nociceptors excited by noxious cold stimuli has been underestimated in previous studies. All nociceptors were excited by stimulus temperatures <0 degrees C and encoded the intensity of cold stimuli. It is therefore likely that cutaneous A delta-nociceptors contribute to the sensation of cold pain, particularly pain produced by stimulus temperatures <0 degrees C.     

Attempts at saving severely ischaemic limbs

The relative efficacy of (1) repeated auditory and somesthetic stimulation for the habituation of cardiac acceleration responses and (2) intramodal and cross-modal stimulation for the dishabituation of cardiac responses was studied in 45 full-term 2-day-old infants. Although the stimuli were equally effective initially, repeated presentation of the somesthetic stimulus had a greater decremental effect than repeated presentation of the auditory stimulus. The stimuli were equally effective in producing dishabituation when in a different modality from that of the habituating stimulus (cross-modal) but not when in the same modality (intramodal). Changes in the locus of stimulation without a change in modality were ineffective for producing dishabituation. The findings indicate the human newborn discriminates auditory and somesthetic inputs effectively and equally but does not discriminate contralateral from ipsilateral stimulation in either modality.     

Cytogenetic and molecular analysis of dynamic mutation associated with fragile X syndrome

The gate control theory of pain (Melzack and Wall, 1965) suggests that tactile stimuli can decrease the perception of pain. We have found the reverse effect: Heat at levels that induce pain can substantially suppress tactile sensitivity, independently of shifts in attention or arousal. Ten human observers were stimulated by a tonic, pain-producing heat stimulus and vibrotactile stimuli (1, 10, and 100 Hz) coincidentally presented to the right thenar eminence. Vibrotactile thresholds were assessed with the skin at a normative temperature of 31 degrees C and at higher temperatures producing pain. Increases in vibrotactile thresholds (mean change = 7.3 dB) occurred at skin temperatures just below and above those that induced pain. Furthermore, absolute-magnitude estimates of suprathreshold vibrotactile stimuli determined during the same experiments showed decreased sensitivity and psychophysical recruitment. The changes are not attributable to attentional or arousal shifts, since they were not associated with changes in auditory thresholds. Furthermore, the changes occurred just below the subjects' pain thresholds (where nociceptors are presumably activated). This over-twofold diminution of vibrotactile sensitivity suggests that heat stimuli capable of inducing pain can significantly diminish taction, perhaps through a "touch gate" in a manner similar to the gate control theory proposed for pain.     

Signal detection and threshold measures for chronic back pain patients, chronic illness patients, and cohort controls to radiant heat stimuli.

15 chronic low back pain patients, 11 chronic respiratory patients, and 11 nonpatient controls (mean ages 47–56 yrs) were studied using a standard radiant heat signal detection methodology. Following determination by ascending limits of each S's stimulus detection and faint pain thresholds, 26 randomized trials at each of 5 stimulus levels were administered. Ss rated each stimulus on a 6-point subjective rating scale ranging from no pain to severe pain. Results indicate that the back pain Ss and respiratory Ss had higher radiant heat pain thresholds than the controls, and the back pain Ss had a discrimination deficit for mildly painful stimuli. Results fit the predictions of an adaptation model of pain perception in chronic pain patients as opposed to a hypochondriasis model. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Myelinated mechanically insensitive afferents from monkey hairy skin: heat-response properties

To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 A beta-fibers, 79 A delta-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors (n = 91) or low-threshold cold receptors (n = 11). Nine A beta-fibers and 41 A delta-fibers were cutaneous nociceptors, and four A delta-fibers innervated subcutaneous tissue. The majority of cutaneous A-fiber nociceptors were heat sensitive (43/50 = 86%). Heat-insensitive cutaneous A-fiber nociceptors consisted of one cold nociceptor, three silent nociceptors, and three high-threshold mechanoreceptors. Two types of response were observed to an intense heat stimulus (53 degrees C, 30 s). Type I (n = 26) was characterized by a long latency (mean: 5 s) and a late peak discharge (16 s). Type II (n = 17) was characterized by a short latency (0.2 s) and an early peak discharge (0.5 s). Type I fibers exhibited faster conduction velocities (25 vs. 14 m/s) and higher heat thresholds (> 53 vs. 47 degrees C, 1-s duration) than type II fibers. The possibility that the type I heat response was a result of sensitization was tested in three fibers by determining the heat threshold to 30-s duration stimuli (42-46 degrees C). For this long stimulus duration heat thresholds were reproducible across multiple runs, and the threshold to the 1-s duration stimulus was not altered by these tests. Thus fibers with a type I heat response were not high-threshold mechanoreceptors that developed a heat response through sensitization. Fibers with a type II heat response had significantly higher mechanical thresholds (median: 15 bar) than fibers with a type I heat response (5 bar). This finding accounts for the observation that type II heat responses were infrequently observed in earlier studies wherein the search technique depended on mechanical responsiveness. Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.     

Numerical analysis of a model of ligand-induced B-cell antigen-receptor clustering. Implications for simple models of B-cell activation in an immune network

Experimental measures of responsiveness to painful and non-painful stimuli as well as measures of typical and present clinical pain were assessed in 26 female patients with fibromyalgia and in an equal number of age-matched healthy women. Pressure pain thresholds, determined by means of a dolorimeter, were lower in the patients compared to the control subjects both at a tender point (trapezius) and at a non-tender control point (inner forearm). The same was true for the heat pain thresholds, measured using a contact thermode. In contrast, the pain thresholds for electrocutaneous stimuli were decreased only at the tender point. The detection thresholds for non-painful stimuli (warmth, cold and electrical stimuli) seemed to be less affected in the fibromyalgia patients, with only the detection threshold for cold being lower at both sites. Tender points were more sensitive than control points for mechanical pressure. The reverse was found for the other modalities which were tested. Although the 3 experimental pain thresholds showed patterns of either generalized or site-specific pain hyperresponsiveness, the between-methods correlations were not very high. While the correlations between the experimental pain thresholds and the various measures of clinical pain (Localized Pain Rating, McGill Pain Questionnaire) in the patients were generally low, there were significant negative correlations between pressure pain thresholds at the two sites and the level of present pain assessed by the Localized Pain Rating. We conclude that a pattern of pain hyperresponsiveness, generalized across the site of noxious stimulation and across the physical nature of the stressor, is associated with fibromyalgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lateral hypothalamus: site involved in pain modulation

The present study is an attempt to examine the neuronal circuitry of a supraspinal site engaged in pain modulation. Five physiological measures were postulated as the criteria for defining a central nervous system site engaged in the circuitry of pain modulation. The lateral hypothalamus met these five measures: (i) 81% of the lateral hypothalamus neurons (247/304) responded to noxious stimuli using a single cell recording procedure; (ii) stimulation of the periaqueductal gray-dorsal raphe area or the habenula modulated 98% and 87% of the lateral hypothalamus noxious-evoked activity; (iii) microiontophoretically applied morphine modulated 77% of the lateral hypothalamus noxious evoked activity; (iv) electrical stimulation of the lateral hypothalamus produced behavioral analgesia proportional to the stimulus intensity as assessed by the tail flick assay; and (v) morphine application into the lateral hypothalamus produced behavioral analgesia in a dose-response manner using the tail flick assay. In conclusion, the lateral hypothalamus can be considered one of the pain modulation sites.     

Shock-induced hyperalgesia: IV. Generality.

Brief-moderate shock (3, 0.75 s, 1.0 mA) has opposite effects on different measures of pain, inducing antinociception on the tail-flick test while lowering vocalization thresholds to shock and heat (hyperalgesia) and enhancing fear conditioned by a gridshock unconditioned stimulus (US). This study examined the generality of shock-induced hyperalgesia under a range of conditions and explored parallels to sensitized startle. Reduced vocalization thresholds to shock and antinociception emerged at a similar shock intensity. Severe shocks (3, 25 s, 1.0 mA or 3, 2 s, 3.0 mA) lowered vocalization threshold to shock but increased vocalization and motor thresholds to heat and undermined fear conditioned by a gridshock or a startling tone US. All shock schedules facilitated startle, but only brief-moderate shock inflated fear conditioning. The findings suggest that brief-moderate shock enhances the affective impact of aversive stimuli, whereas severe shocks attenuate pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Somatovisceral interactions in visceral perception: abdominal masking of colonic stimuli

Clinical and experimental evidence on referred pain and spinal-afferent convergence demonstrates a close relationship between visceral and somatosensory perception, which is important for current models of symptom perception and central body representation. The study uses a psychophysical approach to quantify these interactions at the perceptual level, taking into account problems of comparable intermodal scaling and the role of awareness. An experiment on somatosensory masking of distension stimuli in the colon is reported in which a multiple staircase method of forced choice discrimination with concurrent sensation ratings was employed. Results showed perceptual masking of visceral by abdominal stimuli but not vice versa. The masking effect was not enhanced by intratomal placement of the abdominal stimulus in the lower left quadrant. This contradicts the spinal sensory convergence model and points to perceptual interactions at higher brain levels. Loglinear analysis of relations between discrimination and subjective sensation revealed qualitative differences of somatovisceral perception at the preconscious as compared to the conscious level. This argues for a two-process model of integrative body perception.     

Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys

1. Myocardial ischemia activates vagal and sympathetic cardiac afferent fibers. The purpose of this study was to determine a neuro physiological basis for cardiac pain referred to C1-C3 somatic dermatomes. We hypothesized that afferent fibers traveling in vagal or sympathetic nerves transmit nociceptive information to C1-C3 spinothalamic tract (STT) neurons. 2. Electrical stimulation of the left stellate ganglion to excite cardiopulmonary sympathetic afferent fibers increased extracellular activity of 44 of 77 C1-C3 STT neurons examined in 33 anesthetized male monkeys (Macaca fascicularis); responses increased as stimulus strength increased. Additionally, this stimulus inhibited 5 cells, increased/decreased activity of 2 cells, and did not affect 26 cells. 3. Electrical stimulation of the left (ipsilateral) thoracic vagus nerve excited 41 of 78 C1-C3 STT neurons, inhibited 4 neurons, increased/decreased activity of 2 neurons, and did not affect 31 neurons. Responses increased with increasing stimulus strength Contralateral vagal stimulation excited 7 of 39 cells tested, inhibited 4 cells and did not affect 28 cells. 4. Effects of stimulating one or more vagal branches were examined on 22 C1-C3 STT neurons excited by input from left thoracic vagus nerve. Stimulation of the cardiac branch excited 11 of 16 cells tested; stimulation of the recurrent laryngeal nerve excited 11 of 18 cells; stimulation of vagal fibers just rostral to the diaphragm excited 8 of 19 cells. 5. Excitatory somatic receptive fields ranged from small ipsilateral fields to large, sometimes bilateral or noncontinuous fields. Many fields included the ipsilateral neck and/or inferior jaw. Thirty-nine of 74 neurons examined were wide dynamic range (WDR), 21 were high threshold (HT), 6 were low threshold (LT), and 8 did not respond to brushing or noxious pinching of somatic tissues. Most (38 of 39) WDR cells responded to stimulation of the stellate ganglion or vagal fibers, as did 18 of 21 HT cells, 3 of 6 LT cells, and 2 of 8 cells unresponsive to brush or pinch stimuli. 6. Results of this study supported the concept that vagal and/ or sympathetic afferent activation of C1-C3 STT neurons might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. Additionally, C1-C3 STT neurons processed sensory information from widespread regions of the body.     

Modulatory effects of regional cortical activation on the onset responses of the cat medial geniculate neurons

Corticofugal modulation on activity of the medial geniculate body (MGB) was examined by locally activating the primary auditory cortex (AI) and looking for effects on the onset responses of MGB neurons to acoustic stimuli. Of 103 MGB neurons recorded from 13 hemispheres of 11 animals, 91 neurons (88%) showed either a facilitatory or inhibitory effect or both; of these neurons, 72 showed facilitatory effects and 25 inhibitory effects. The average facilitatory effect was large, with a mean increase of 62.4%. Small inhibitory effects (mean: -16.2%) were obtained from a few neurons (6 of 103) when a pure tone stimulus was used, whereas the effect became larger and more frequent when a noise burst stimulus was used (mean: -27.3%, n = 22 of 27 neurons). Activation of an AI site having the same best frequency (BF) as the MGB neuron being recorded from produced mainly a facilitatory effect on MGB neuronal responses to pure tones. Activation of AI at a site neighboring the BF site produced inhibitory effects on the MGB response when noise burst stimuli were used. We found that the effective stimulation sites in AI that could modulate MGB activity formed patchlike maps with a diameter of 1.13 +/- 0.09 (SE) mm (range 0.6-1.9 mm, n = 15) being larger than the patches of thalamocortical terminal fields. Examining the effects of sound intensities, of 18 neurons tested 9 neurons showed a larger effect for low-sound-intensity stimuli and small or no effects for high-sound-intensity stimuli. These were named low-sound-intensity effective neurons. Five neurons showed high sound intensity effectiveness and four were non-intensity specific. Most low-sound-intensity effective neurons were monotonic rate-intensity function neurons. The AI cortical modulatory effect was frequency specific, because 15 of 27 neurons showed a larger facilitatory effect when a BF stimulus was used rather than a stimulus of any other frequency. The corticothalamic connection between the recording site in MGB and the most effective stimulation site in AI was confirmed by injecting wheat germ agglutinin-horseradish peroxidase tracer at the stimulation site and producing a small lesion in the recording site. The results suggest that 1) the large facilitation effects obtained by AI activation at the region that directly projected to the MGB could be the result mainly of the direct projection terminals to the MGB relay neurons; 2) the large size patches of the effective stimulation site in AI could be due to widely ramifying corticothalamic projections; and 3) the corticofugal projection selectively gates auditory information mainly by a facilitatory effect, although there is also an inhibitory effect that depends on the sound stimulus used.     

Analgesic effects induced by TENS and electroacupuncture with different types of stimulating electrodes on deep tissues in human subjects

Effects of conditioning peripheral nerve stimulation with different types of stimulating electrodes on pain thresholds in various deep tissues were measured in human subjects. Cone-shaped metal (phi 13 mm), rubber (phi 13 mm), and large soft surface electrodes (50 x 150 mm) were used for transcutaneous electrical nerve stimulation (TENS), and insulated and non-insulated acupuncture needles (diameter: 240 microns) were used for electroacupuncture (EA). Two pairs of electrodes were placed around the point of deep pain measurement. Symmetrical positive and negative square pulses (0.1 msec at 100 Hz) of just below the pain tolerance intensity were used for both TENS and EA. Deep pain thresholds were measured at the center of the thigh with a pulse algometer and insulated needle electrodes. Pain thresholds of deep tissues were in the order periosteum < fascia < skin (including subcutaneous tissues) < muscle. TENS with surface electrodes significantly increased pain thresholds of skin and fascia but not those of muscle or periosteum. The shape, material and size of the surface electrodes hardly affected the degree of analgesic effect, except in the fascia by large soft electrodes. In contrast, EA with non-insulated needles induced a greater increase in pain threshold in skin, fascia and muscle, although statistically significant results were obtained in only the first two tissues. EA with insulated needle electrodes was the only technique with which we obtained a significant increase in pain threshold in muscle and periosteum. These results suggest that the choice of electrode and stimulus parameters is important for the production of sufficient analgesic effects in different somatic tissues and that insulated needle electrodes are useful for pain relief in deeper tissues such as muscle and periosteum.