Neuronal responses to stimulation of the cervix, uterus, colon, and skin in the rat spinal cord

1993 ◽  
Vol 69 (2) ◽  
pp. 545-556 ◽  
Author(s):  
K. J. Berkley ◽  
C. H. Hubscher ◽  
P. D. Wall

1. Previous studies in the rat have shown that the hypogastric nerve conveys input from the cervix and uterus mainly to the T13-L3 segments of the spinal cord, whereas the pelvic nerve conveys input from the cervix and vaginal canal mainly to the L6-S2 segments. 2. To study the effects of this input, the dorsal horns of the T13-L1, L6-S2, and L4-L5 segments in 13 decerebrate, T10-spinalized, unanesthetized, and paralyzed adult female rats in estrus were searched for neurons responsive to gentle mechanical stimulation of the cervix. The 87 neurons found were then further tested for their responses to gentle mechanical stimulation of the skin and to distension of both uterine horns, distension of the colon, and shearing stimulation of the colon and vaginal canal. 3. Neurons responsive to cervix stimulation, primarily by excitation, were readily found in the ventral part of the dorsal horn in T13-L1 and throughout the dorsal horn in L6-S2. Cervix-responsive neurons were less readily found throughout the dorsal horn in L4-L5, where 25% were inhibited by the stimulation. All but one neuron had cutaneous receptive fields. 4. The 30 cervix-responsive neurons in T13-L1 had large bilateral cutaneous receptive fields covering the perineum and hind-limbs. Most (76%) also responded, primarily by excitation, to uterine distension, as well as to colonic stimulation (59%). More than half were activated by both types of stimulation. 5. The 33 cervix-responsive neurons in L6-S2 had cutaneous receptive fields in the same regions as those in T13-L1, but generally smaller, particularly for neurons in the dorsal part of the dorsal horn, many of whose receptive fields were confined to the perineum. The L6-S2 neurons also exhibited less convergent input from other visceral structures, particularly the uterus. Fewer neurons (42%) responded to uterine distension, mostly by being inhibited, whereas about the same proportion (51%) responded with excitation to colonic stimulation. Only 24% responded to both uterus and colon. 6. All 24 cervix-responsive neurons in medial L4-L5 had small cutaneous receptive fields on the toes, and the neurons received less convergent input from other visceral structures (25% from the uterus, 33% from the colon, 13% from both). 7. These results indicate the presence of an extensive system of neurons throughout the caudal spinal cord of the rat, concentrated in separated thoracolumbar and lumbosacral segments, that is concerned with input from the reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS)

1990 ◽  
Vol 64 (1) ◽  
pp. 299-311 ◽  
Author(s):  
V. Neugebauer ◽  
H. G. Schaible

1. In the spinalized cat, nociceptive spinal neurons with knee input show enhanced responses to mechanical stimulation of that joint once an inflammation has developed in the knee. Enhanced responses may result from increased afferent inflow as well as from modifications of the nociceptive processing within the spinal cord. To examine the significance of these components, we tested in 30 chloralose-anesthetized, spinalized cats whether, during development of arthritis, changes of responsiveness in spinal neurons are restricted to stimulation of the inflamed joint or whether responsiveness in these neurons is altered in general. While continuously recording from a neuron, we injected kaolin and carrageenan into one knee and tested the responses to mechanical stimuli applied to the joint and to regions adjacent to and remote from the knee during the developing arthritis. In addition, in six cats we monitored the neurons' responses to electrical stimulation of the sural nerves and the rostral lumbar spinal cord. 2. Of 32 neurons in laminae VI, VII, and VIII of the lumbar spinal cord, 15 ascending and eight nonascending cells were driven by mechanical stimulation of one or both knee joint(s). Nine of these were nociceptive specific (NS), responding exclusively or predominantly to noxious compression of the knee and other deep tissue, and 12 were wide-dynamic-range (WDR) cells with graded responses to gentle and noxious stimuli applied to the knee joint(s), deep tissue, and skin. Two neurons with high ongoing discharges had some excitatory joint input but showed marked inhibition by most stimuli used (INH neurons). The majority of the neurons had receptive fields on both legs. Nine of the 32 neurons had no input from the knee(s). 3. All 23 neurons with joint input became sensitive or more responsive to movements and gentle compression of the inflamed knee once the inflammation had developed. In general, these neurons also showed enhanced responses to compression of the adjacent muscles in thigh and lower leg. In 20 neurons, response properties were even altered for stimuli applied to regions remote from the inflamed joint, including the contralateral leg in 18 cases. We found expansion of initially restricted receptive fields (mainly in NS cells), enhancement of preexisting responses, and/or lowering of threshold to mechanical stimuli applied to these regions; few neurons developed inhibitory reactions.(ABSTRACT TRUNCATED AT 400 WORDS)


1990 ◽  
Vol 63 (2) ◽  
pp. 256-272 ◽  
Author(s):  
K. J. Berkley ◽  
H. Hotta ◽  
A. Robbins ◽  
Y. Sato

1. Electrophysiological techniques were used to characterize responses of afferent fibers in pelvic nerve of adult, virgin female rats to mechanical or chemical stimulation of internal reproductive organs and to mechanical stimulation of other pelvic organs. 2. In an in vivo barbiturate-anesthetized preparation, pelvic nerve afferent fibers responded to a wide variety of mechanical stimulation applied to restricted regions of the vaginal canal, caudal uterus (body and cervix), bladder, ureter, colon, or anus. 3. Single-fiber mechanoreceptive fields were invariably confined to a single organ. Notably, responses could be evoked not only by gentle stimulation of the unit's receptive field directly on the organ itself, but also by stimulating the field indirectly with intense stimulation through the appropriate part of a contiguous organ. This innervation feature is consistent with the separability of pelvic organ functions under innocuous conditions but their confusion under noxious ones. 4. Receptive fields on the reproductive organs extended from the caudal edge of the vagina to the uterine body (including the cervix) but were most often located in the fornix (vaginocervical junction). Most units had no or low levels of spontaneous activity. Their responses to mechanical stimuli were usually slowly or moderately adapting and time-locked to the stimulus. 5. Fibers with vaginal receptive fields (including the fornix) responded best either to vaginal distension with a balloon or, more often, to a probe moving along the internal vaginal surface in a direction toward the cervix. They were observed most frequently during the proestrus stage of the rat's estrous cycle. These fibers, therefore, seem particularly suited for relaying information about stimuli that occur during mating. 6. Fibers with receptive fields on the uterine cervix and body responded best to static pressure and were observed less frequently than those with vaginal fields, regardless of estrous stage. They were, however, sensitized by hypoxia. In addition, irritation of the uterus increased the probability of observing them. These fibers, therefore, may exert their primary function during reproductive conditions different from those of virgin rats, such as parturition. 7. Response activity of most of the mechanoreceptive afferent fibers supplying reproductive organs increased as the stimulus intensity increased into the noxious range; i.e., into a range in which the stimulus momentarily produced ischemia at the stimulus site. In addition, in an in vitro preparation, pelvic nerve fibers responded in a dose-dependent manner to injections through the uterine artery of bradykinin (BRAD) as well as to other algesic chemicals, 5-hydroxytryptamine (5-HT) and KCl.(ABSTRACT TRUNCATED AT 400 WORDS)


1991 ◽  
Vol 66 (1) ◽  
pp. 261-284 ◽  
Author(s):  
R. Burstein ◽  
R. J. Dado ◽  
K. D. Cliffer ◽  
G. J. Giesler

1. Ninety-six neurons in the lumbar enlargement of urethananesthetized rats were antidromically activated from the contralateral hypothalamus. The antidromic stimulating electrode was moved systematically within the hypothalamus until antidromic activation could be produced with currents of less than or equal to 50 microA (18.6 +/- 10.8 microA; mean +/- SD). The points at which antidromic activation thresholds were lowest were found in several regions of the hypothalamus but were concentrated in the optic tract and the supraoptic decussation. 2. The recording locations of 79 spinohypothalamic tract (SHT) neurons were marked and recovered. Twenty-nine were located in the superficial dorsal horn (SDH), 42 in the deep dorsal horn (DDH), 4 in the intermediate zone, and 2 in the gray matter surrounding the central canal. Two additional marks were located in the dorsal lateral funiculus (DLF). 3. The responses of 46 SHT neurons were examined during innocuous and noxious mechanical stimulation of their receptive fields. Forty-eight percent of recorded SHT neurons responded to both innocuous and noxious stimuli (wide dynamic range, WDR) and 39% responded only to noxious stimuli (high threshold, HT). Therefore 87% of SHT neurons responded preferentially or exclusively to noxious mechanical stimulation. Nine percent of SHT neurons responded exclusively to innocuous manipulation of joints and muscles. Four percent of SHT neurons responded only to innocuous tactile stimul (low threshold, LT). WDR, HT, and LT neurons were recorded widely throughout the dorsal horn; no relationship was found between the locations of recording sites in the dorsal horn and the response types of the neurons. SHT neurons that responded to stimulation of muscle, tendon, or joint were recorded deep in the gray matter. 4. The effects of heating the receptive fields were determined for 25 SHT neurons. Fourteen (56%) responded to thermal stimuli. Six (43%) of the responsive neurons responded at low frequencies to innocuous warming (38-41 degrees C) but more vigorously to noxious (greater than or equal to 45 degrees C) heating. The other eight responded only to noxious heat. Eighteen percent (3/17) of tested SHT neurons were activated by noxious cooling of their receptive fields. 5. Cutaneous receptive fields of most recorded SHT neurons were small, typically involving areas as small as two or three toes on the ipsilateral hindlimb; the largest receptive fields covered the entire paw. These findings indicate that relatively precise information about the location of innocuous and noxious stimuli is conveyed directly to the hypothalamus by SHT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)


1992 ◽  
Vol 68 (2) ◽  
pp. 384-391 ◽  
Author(s):  
J. X. Hao ◽  
X. J. Xu ◽  
Y. X. Yu ◽  
A. Seiger ◽  
Z. Wiesenfeld-Hallin

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)


1993 ◽  
Vol 69 (6) ◽  
pp. 2072-2085 ◽  
Author(s):  
J. M. Laird ◽  
G. J. Bennett

1. Extracellular single-unit recordings have been made from 295 dorsal horn neurons in the lumbar enlargement of rat spinal cord; 191 neurons in 20 rats with an experimental peripheral neuropathy, and 104 in 10 sham-operated rats. Recordings were made 9-11 days after inducing the neuropathy by tying four loose ligatures around the sciatic nerve in the nerve-injured rats or performing a sham procedure in the sham-operated rats. 2. A survey of the general properties of all neurons encountered was made in the 10 sham-operated rats (104 neurons) and compared with those seen in 17 of the nerve-injured animals (180 neurons). The vast majority (87%; 156/180) of neurons recorded in the nerve-injured animals showed abnormal characteristics; these included responses to very gentle mechanical stimulation of the nerve-injury site and to manipulations that resulted in movement of this site such as extension of the leg and probing of the skin and muscle of the thigh (53%), absence of detectable peripheral receptive fields (RFs; 56%), and very high spontaneous activity (7%). In the sham-operated rats none of the neurons recorded could be activated by gentle mechanical stimulation of the sciatic nerve, and only 6% had no detectable peripheral RF. 3. In the nerve-injured animals, 31% (55/180) of cells had both a peripheral RF, and a response to gentle mechanical stimulation of the nerve-injury site. All cells of this type tested (n = 5) showed very prolonged responses (up to 10 min long) to 15 s pinch stimuli applied to the RF and to 15 s gentle tapping of the injury site. The majority of cells in this group were excited by noxious stimuli (71%; 39/55) and had C-fiber inputs (60%; 33/55). 4. The mean threshold temperatures for evoking responses to heat stimuli in cells tested in nerve-injured rats and in sham-operated animals were not different. However, there was a group of neurons in the nerve-injured rats that had low thresholds, failed to encode stimulus intensity, and did not have a C-fiber input. 5. There were significantly fewer neurons excited by low-intensity stimulation of the skin in the nerve-injured (24%; 43/180) than in the sham-operated rats (71%; 74/104). Measurements of mechanical threshold with von Frey hairs showed that, although the mean threshold did not change, none of the cells tested in the nerve-injured animals had thresholds < 12 mN, whereas the lowest threshold recorded in the sham-operated animals was 0.2 mN.(ABSTRACT TRUNCATED AT 400 WORDS)


2006 ◽  
Vol 96 (2) ◽  
pp. 661-670 ◽  
Author(s):  
Esther Garcia-Nicas ◽  
Jennifer M. A. Laird ◽  
Fernando Cervero

Single-unit electrical activity was recorded from 80 nociceptor-specific (NS) neurons in the dorsal horn of the lumbar spinal cord of pentobarbital anesthetized rats. Their responses to low- and high-intensity mechanical stimulation of their receptive fields (RFs) were recorded before and after the application of irritant agents [capsaicin (CAP) or mustard oil (MO)] to the RF. Before the applications of the irritants the neurons responded only to high-intensity stimuli, but after this procedure 20 of 28 neurons tested were sensitized, i.e., gave increased responses to high-intensity stimuli and showed novel responses to low-intensity mechanical stimulation as well as an Aβ-fiber afferent drive. CAP was more likely to induce sensitization than MO and the majority of sensitized neurons were located in the superficial dorsal horn. No relationship was found between the magnitude of the response to the sensitizing agent and the presence or absence of sensitization. Cumulative doses of two γ-aminobutyric acid type A (GABAA)–receptor antagonists, picrotoxin and bicuculline, were administered systemically or applied directly over the spinal cord. The GABAA antagonists reversed the sensitization of the neurons by reducing the novel low-threshold responses. These results show that NS neurons in the spinal dorsal horn can be sensitized by a sustained afferent discharge in peripheral nociceptors and that this sensitization can be reduced or reversed by low doses of GABAA-receptor antagonists. This provides evidence for a mechanism in which an enhanced GABAergic transmission can lead to hyperexcitability and sensitization of NS neurons in the dorsal horn.


1986 ◽  
Vol 55 (4) ◽  
pp. 635-643 ◽  
Author(s):  
P. Grigg ◽  
H. G. Schaible ◽  
R. F. Schmidt

Recordings were performed from sciatic nerve or dorsal root filaments in 28 cats to study single group III (conduction velocity 2.5-20 m/s) and group IV (conduction velocity less than 2.5 m/s) units supplying the knee joint via the posterior articular nerve (PAN). In seven of these cats the knee joint had been inflamed artificially. Recordings from sciatic nerve filaments revealed responses to local mechanical stimulation of the joint in only 3 of 41 group IV units and in 12 of 18 group III units from the normal joint. In the inflamed joint 14 of 36 group IV units and 24 of 36 group III units were excited with local mechanical stimulation. In recordings from dorsal root filaments (normal joint) 4 of 11 group IV units and 7 of 13 group III units were activated by stimulating the joint locally. In the normal joint four group IV units (recorded from dorsal root filaments) responded only to rotations against the resistance of the tissue, whereas the majority of the fibers did not respond even to forceful movements. Group III units with local mechanosensitivity in the normal joint reacted strongly or weakly to movements in the working range of the joint or only to movements against resistance of the tissue. In the inflamed joint, group IV fibers (recorded in sciatic nerve filaments) with detectable receptive fields responded strongly to gentle movements or only to movements against resistance of tissue. Some did not react to movements. Group III units reacted strongly or weakly to gentle movements or only to movements against resistance of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Sensors ◽  
2022 ◽  
Vol 22 (2) ◽  
pp. 501
Author(s):  
Seunghyeon Yun ◽  
Chin Su Koh ◽  
Jungmin Seo ◽  
Shinyong Shim ◽  
Minkyung Park ◽  
...  

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.


2008 ◽  
Vol 99 (6) ◽  
pp. 3144-3150 ◽  
Author(s):  
Rachel A. Ingram ◽  
Maria Fitzgerald ◽  
Mark L. Baccei

The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of γ-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced afterdischarge.


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