Neonatal bladder inflammation alters activity of adult rat spinal visceral nociceptive neurons

Purpose: This investigation examined the effect of inflammation produced by intravesical zymosan during the neonatal period on spinal dorsal horn neuronal responses to urinary bladder distension (UBD) as adults. Methods: Female rat pups (P14–P16) were treated with intravesical zymosan or with anesthesia-only. These groups of rats were subdivided forming four groups: half received intravesical zymosan as adults and half received anesthesia-only. One day later, rats were anesthetized, the spinal cord was transected at a cervical level and extracellular single-unit recordings of L6-S1 dorsal horn neurons were obtained. Neurons were classified as Type I—inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II – not inhibited by HNCS – and were characterized for Spontaneous Activity and responses to graded UBD (20–60 mm Hg). Results: 227 spinal dorsal horn neurons excited by UBD were characterized. In rats treated as neonates with anesthesia-only, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following adult intravesical zymosan treatment whereas Type I neurons demonstrated decreased spontaneous and UBD-evoked activity relative to controls. In rats treated as neonates with intravesical zymosan, the spontaneous and UBD-evoked activity of both Type I and Type II neurons increased following adult intravesical zymosan treatment relative to controls. Conclusions: Neonatal bladder inflammation alters subsequent effects of acute bladder inflammation on spinal dorsal horn neurons excited by UBD such that overall there is greater sensory neuron activation. This may explain the visceral hypersensitivity noted in this model system and suggest that impaired inhibitory systems may be responsible.     

Interactions between visceral and cutaneous nociception in the rat. II. Noxious visceral stimuli inhibit cutaneous nociceptive neurons and reflexes

1. Nocigenic inhibition is the inhibition of neural, behavioral, or reflex responses to a nociceptive test stimulus produced by another, conditioning, nociceptive stimulus. The present study examines whether a natural noxious visceral stimulus, colorectal distension, used as a conditioning stimulus would inhibit neuronal or reflex responses to noxious cutaneous stimuli. Segmental effects of colorectal distension have been previously characterized; hence conditioning effects of colorectal distension on stimuli applied at sites distant (heterosegmental effects) and adjacent (perisegmental effects) to those areas of the spinal cord that receive the greatest afferent input from the colon were examined. The conditioning effects of colorectal distension were compared with those of noxious pinch. 2. Heterosegmental effects of colorectal distension were studied in 129 neurons located in the area of the trigeminal nucleus caudalis and cervical spinal dorsal horn. Steady-state activity (spontaneous activity or activity evoked by sustained pressure) of 106 of 129 trigeminal-cervical dorsal horn neurons was inhibited by both noxious colorectal distension (100 mmHg, 20 s) and noxious pinch of the tail; all neurons inhibited by colorectal distension were also inhibited by noxious pinch. Inhibition was graded with the intensity of the distending stimulus. The class 2-class 3 classification system (neurons excited by nonnoxious and noxious or only by noxious cutaneous stimuli, respectively) was roughly predictive of susceptibility to nocigenic inhibition, because 74 of 75 class 2 neurons tested were inhibited by noxious colorectal distension or noxious pinch and only 32 of 54 class 3 neurons were similarly inhibited. Five neurons were excited by colorectal distension, all of which were class 3 neurons. 3. Perisegmental effects of colorectal distension were observed in 100 L3-L5 spinal dorsal horn neurons. The spontaneous activities and responses during noxious test heating of the glabrous skin of the hindpaw of these neurons were affected in the same way by noxious (conditioning) colorectal distension. All neurons inhibited by colorectal distension (51 class 2 and 8 class 3 neurons) were also inhibited by noxious pinch of the nose or forepaw. The magnitude of the nocigenic inhibition of responses during heating of the hindpaw was graded with the intensity and duration of the noxious conditioning colorectal distension, was a function of the number of preceding distensions given to the rat, and outlasted the distending stimulus. Conditioning colorectal distension also produced a parallel shift to the right in stimulus-response functions relating responses of neurons to the intensity of the noxious test stimulus (42-50 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute bladder inflammation differentially affects rat spinal visceral nociceptive neurons

The present investigation examined the effect of inflammation produced by intravesical zymosan on spinal dorsal horn neuronal responses to urinary bladder distension (UBD). Extracellular single-unit recordings of neurons excited by UBD were obtained in spinalized female Sprague–Dawley rats. Neurons were classified as Type I—inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II—not inhibited by a HNCS. In Experiment 1—following neuronal characterization, 1% zymosan was infused into the bladder and after 2 h spinal units were recharacterized. Control rats received intravesical saline or subcutaneous zymosan. In Experiment 2—rats were pretreated with intravesical zymosan 24 h prior to surgical preparation. Control rats received anesthesia only. 137 spinal dorsal horn neurons excited by UBD were characterized. In comparison with controls, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following intravesical zymosan treatment (both Experiments 1 and 2) whereas Type I neurons demonstrated either no change (Experiment 1) or decreased activity (Experiment 2) following bladder inflammation. No significant changes were noted in neuronal activity in control experiments. Inflammation differentially affects subpopulations of spinal dorsal horn neurons excited by UBD that can be differentiated according to the effect of HNCS. This results in an altered pattern of spinal sensory transmission that may serve as the mechanism for the generation of visceral nociception.     

Responses of reticulospinal neurons in the lateral reticular nucleus area of the rat to cutaneous noxious and non-noxious stimulation

Response properties of reticulospinal neurons in the lateral reticular nucleus (LRN) area to natural cutaneous stimulation were investigated systematically in 45 urethane-anesthetized rats by using extracellular recording techniques. A total of 64 neurons were tested with peripheral stimuli, of which 19 were responsive only to noxious stimuli; 7 responsive to both noxious and non-noxious stimuli; 4 responsive only to non-noxious stimuli; and 34 not responsive to any cutaneous stimuli. Both the noxious and non-noxious receptive fields were large and bilateral. Among the neurons responding to noxious stimuli, the majority (72%) was excited. This study provides evidence that some reticulospinal neurons in the rat LRN area are involved in the mechanisms of nociception.     

Spinal neuronal responses to urinary bladder stimulation in rats with corticosterone or aldosterone onto the amygdala

Elevating glucocorticoids in the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. The aim of this study was to determine if descending modulation from the amygdala affects spinal processing of input from urinary bladder afferents. Fischer-344 rats received cholesterol (inactive control)-, corticosterone-, or aldosterone-containing micropellets placed stereotaxically on the dorsal margin of the left and right amygdala (n = 10 for each group). Seven days after amygdaloid implantation, extracellular potentials of single L6-S1 spinal neurons were examined for the responses to graded (0.5-2.0 ml, 20 s) urinary bladder distension (UBD). Spontaneous activity of neurons with excitatory responses to UBD in aldosterone-implanted rats [11.0 +/- 1.7 (SE) imp/s], but not in corticosterone-implanted rats, was higher than in the cholesterol-implanted group (6.6 +/- 1.1 imp/s, P < 0.05). Noxious UBD (1.5 ml) produced a greater excitatory response (21.6 +/- 2.6 imp/s) in aldosterone-implanted rats compared with cholesterol- or corticosterone-implanted rats (15.1 +/- 1.5 and 13.6 +/- 1.4 imp/s; P < 0.05). In contrast, the duration of excitatory responses to UBD in corticosterone-implanted rats (38.5 +/- 3.4 imp/s) was significantly longer than those in the aldosterone or control groups (26.8 +/- 1.8 and 24.7 +/- 1.5 imp/s). Neurons with low thresholds for excitatory responses to UBD were seen more frequently in aldosterone-implanted rats than in corticosterone or cholesterol treated rats (74 vs. 44% and 39%, P < 0.05). No difference in somatic field properties of spinal neurons responsive or nonresponsive to UBD was found among the three groups. These findings suggest that both mineralocorticoid- and glucocorticoid-mediated mechanisms in the amygdala are involved in descending modulation to lumbosacral spinal neurons receiving inputs from the urinary bladder; and this mechanism may play a role in the activation and maintenance of primary central sensitization to noxious visceral stimuli.     

Cerebellar cortical stimulation increases spinal visceral nociceptive responses

The role of the cerebellum in modulating nociceptive phenomena is unclear. In this study, we focus on the effects of cerebellar cortical stimulation on the responses of midline neurons of the lumbosacral spinal cord to graded nonnoxious and noxious visceral (colorectal distension) as well as somatic (brush, pressure, pinch) stimuli. Extracellular recording was used for the isolation and recording of spinal nociceptive neurons, while electrical current pulses and chemical injection of D, L-homocysteic acid were used to stimulate the cortex of the posterior cerebellar vermis. Cerebellar cortical stimulation increased the responses of all isolated cells to colorectal distension, whereas the effect on the responses to somatic stimuli was variable. These findings indicate that the posterior cerebellar vermis may exert a pro-nociceptive effect on spinal visceroceptive neurons.     

Characterization of neuronal responses to noxious visceral and somatic stimuli in the medial lumbosacral spinal cord of the rat

The cutaneous receptive fields, long ascending projections, and responses to colorectal distension (20-100 mmHg) and tail movement of 252 neurons in spinal segments L6-S1 were characterized in pentobarbital- or halothane-N2O anesthetized, physiologically intact male rats. Seventeen additional neurons were studied in spinalized rats. Neurons studied were located within 0.5 mm of the midline at depths 0.2-1.4 mm from the spinal cord dorsum and included the area immediately dorsal and lateral to the central canal. Colorectal distension and/or antidromic invasion from the contralateral ventral quadrant of the cervical spinal cord were used as search stimuli. One hundred seventeen neurons responded to noxious colorectal distension; many had long ascending projections and convergent somatic input from deep joint receptors, ipsilateral perianal/scrotal cutaneous receptive fields, or both. Stimulus-response functions (SRFs) of 45 neurons to graded colorectal distension were linear, allowing extrapolation of threshold distending pressures to neuronal response. Neurons responsive to colorectal distension were subdivided into four classes based on their initial response colorectal distension (75-80 mmHg, 20 s). Short-latency abrupt (SL-A) neurons were excited at short latency by colorectal distension; activity abruptly returned to base line following termination of distension. Most SL-A neurons had long ascending projections, convergent somatic receptive fields, and 4/6 tested were excited by bradykinin administered intraarterially. The threshold distending pressure, estimated from the SRFs of 19 SL-A neurons, extrapolated to 2.7 mmHg. Short-latency sustained (SL-S) neurons were also excited at short latency by colorectal distension, but responses were sustained for 4-120 s following termination of distension. Most SL-S neurons had long ascending projections, convergent somatic receptive fields, and 18/20 tested were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of 20 SL-A neurons, extrapolated to 17.0 mmHg. Long-latency (LL) neurons were excited by colorectal distension at long latency following the onset of distension. No LL neurons had demonstrable long ascending projections, and few had convergent excitatory somatic fields. Three of five LL neurons were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of six LL neurons, extrapolated to 9.8 mmHg. Inhibited (INHIB) neurons were spontaneously active and were inhibited by colorectal distension.(ABSTRACT TRUNCATED AT 400 WORDS)     

脊髓下丘脑和脊髓丘脑束神经元在内脏痛传导中的作用

脊髓下丘脑束在从脊髓向间脑和脑干的信息传递过程中起着重要作用.我们对脊髓下丘脑束是否参与了大鼠内脏痛信号传导过程的研究结果显示,在所有被检测的腰段和骶段脊髓下丘脑束和脊髓丘脑束神经元中,随着对结肠、直肠和(或)阴道的强制性扩张刺激强度的增加,三分之一以上神经元的放电频率逐级增加.在所检测的下位胸段脊髓神经元中,约二分之一的脊髓下丘脑束神经元可通过逐级扩张胆管被激活,且这些神经元的反应高度符合加速函数曲线.结果 提示,在应对内脏器官伤害性扩张的微小变化时,这些神经元的放电频率明显增加.同时表明,脊髓下丘脑束在从脊髓到大脑广泛区域伤害性内脏感觉信息的直接传递过程中起着重要作用.     

Quantitative characterization and spinal pathway mediating inhibition of spinal nociceptive transmission from the lateral reticular nucleus in the rat

1. The modulation of spinal nociceptive transmission from the lateral reticular nucleus (LRN) was characterized for 47 spinal dorsal horn neurons in pentobarbital-anesthetized, paralyzed rats. All 47 units studied had receptive fields confined to the glabrous skin of the plantar surface of the ipsilateral hind foot and responded to mechanical stimulation as well as noxious heating (50 degrees C). Rostral projections contained in the ventrolateral quadrant of the cervical spinal cord were demonstrated for 15 of the 47 units by antidromic invasion. Glutamate- and stimulation-produced descending inhibition, the spinal pathway, and tonic descending inhibition from the LRN were systematically examined. 2. Inhibition of unit responses to heating of the skin by electrical stimulation in the LRN varied with the intensity, pulse duration (100 or 400 microseconds), and frequency (25-100 Hz) of stimulation. Greater inhibition was produced at lower intensities of stimulation with the 400-microseconds pulse duration and a frequency of 100 Hz. The effects of stimulation on spontaneous activity and responses to heat were compared in 16 experiments; inhibition of spontaneous activity was intensity dependent and did not differ significantly in magnitude from stimulation-produced inhibition of responses to heating of the skin. 3. Tracking experiments established that stimulation in the ipsilateral and contralateral ventrolateral medulla reliably attenuated unit responses to noxious heating of the skin and that stimulation in the LRN produced maximal inhibition at a low intensity of stimulation. Descending inhibition was quantitatively characterized from sites within (n = 32) and outside (n = 30) the LRN. Both the extrapolated mean stimulation threshold for inhibition and mean intensity inhibiting unit responses to heat to 50% of control were significantly lower for sites in the LRN. 4. The responses of seven spinal units to graded noxious heating of the skin were studied; all exhibited linear monotonic stimulus-response functions (SRFs) throughout the temperature range examined (42-50 degrees C). Electrical stimulation in the LRN significantly decreased the slope (42 +/- 4% of control) of the SRFs and increased the neuronal response threshold (2.0 +/- 0.7 degrees C). 5. S-glutamate (50 nmol, 0.5 microliter) was microinjected into stimulation sites within (n = 15) and distant from (n = 6) the LRN. Glutamate produced a transient (less than 7 min) but significant attenuation of neuronal responses to heat to 35 +/- 6% of control only when microinjected into the LRN.(ABSTRACT TRUNCATED AT 400 WORDS)     

Quantitative comparison of inhibition of visceral and cutaneous spinal nociceptive transmission from the midbrain and medulla in the rat

1. The descending inhibition of neuronal responses by focal electrical stimulation or glutamate microinjections in the periaqueductal gray (PAG) or rostral ventromedial medulla (RVM) was quantitatively studied on 61 spinal neurons in halothane-N2O-anesthetized paralyzed rats. Thirty-six neurons were located in the medial L6-S1 spinal cord and were consistently and reproducibly excited by distension of the descending colon and rectum (75 mmHg). Twenty-five other neurons were located in the dorsal horn of spinal segments L3-L5 and were consistently and reproducibly excited by radiant heating (50 degrees C) of the glabrous skin of the plantar surface of the left (ipsilateral) hind foot. 2. The inhibition of neuronal responses to colorectal distension by stimulation in the PAG or RVM differed quantitatively when examined on the same spinal neurons. Inhibition of neuronal responses to distension occurred at a lower mean threshold of stimulation in the RVM than in the PAG. The mean intensity of stimulation in the RVM producing an attenuation to 50% of the control response to colorectal distension (75 mmHg, 20 s) was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the RVM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the RVM and PAG produced the same mean percent change in inhibition per 25-microA increase in the intensity of stimulation. Thus the slopes of the lines of recruitment of descending inhibition from the PAG and RVM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. These findings are virtually identical to those found by others in studies of modulation of neuronal responses to noxious heating of the skin. 3. Neuronal intensity coding to both graded heating of the hindfoot and graded colorectal distension was montonus and accelerating and could be expressed as linear stimulus-response functions (SRFs) in the temperature and pressure ranges studied (46-52 degrees C, 25-100 mmHg). Stimulation in the PAG modulated the SRFs differently than did stimulation in the RVM. Stimulation in the PAG decreased the slope of the SRFs without affecting the units' thresholds of response, thus influencing the gain control of both cutaneous and visceral nociception in the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urinary bladder and hindlimb afferent input inhibits activity of primate T2-T5 spinothalamic tract neurons

1. Extracellular recordings were made from 41 spinothalamic tract (STT) neurons on the left side of the T2-T5 spinal segments of 20 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Manipulation of the left triceps-chest region and electrical stimulation of cardiopulmonary sympathetic afferent fibers excited these cells. 2. Isotonic urinary bladder distensions (UBD) to pressures between 20 and 80 cmH2O reduced the spontaneous activity in 33 of 41 cells. Cell activity was significantly reduced by UBD at 20 cmH2O. Distensions to 40, 60, and 80 cmH2O produced progressively greater reductions in spontaneous discharge. Activity was decreased throughout distension in 29 cells (tonic inhibition) and at the onset of distension in 3 neurons (phasic inhibition). In one cell, inhibition followed a brief excitation at the onset of distension (phasic excitation-tonic inhibition). Spontaneous bladder contractions also inhibited STT cell activity. 3. Inhibition by UBD was observed in STT cells characterized as wide dynamic range, high threshold, and high threshold inhibitory. No correlation existed between cell type or laminar location and inhibition by urinary bladder distension. Cells excited by cardiopulmonary sympathetic afferent A delta- and C-fibers had a significantly greater tendency to be inhibited by UBD (17 of 18) than cells activated by A delta- but not C-fibers (13 of 20). 4. Urinary bladder distension and pinch of the hindlimbs also reduced activity of STT cells excited by input from cardiopulmonary sympathetic afferents and from the proximal forelimb. 5. Urinary bladder distension to 40, 60, or 80 cmH2O produced a greater absolute but smaller relative reduction in the firing frequency of STT cells as spontaneous activity increased. Thus the magnitude of this inhibitory effect may depend on whether the inhibitory effect is measured as an absolute or relative change in cell activity. 6. Convergent inhibitory input from somatic regions also was observed. Noxious pinch of the hamstring region of the right hindlimb decreased activity in 32 of 39 cells. Left hindlimb pinch inhibited 21 of 38 cells, and 15 of 29 cells were inhibited by right triceps pinch. 7. Convergent inhibitory input from the hamstring region of the hindlimbs and from the urinary bladder to upper thoracic STT cells may be important for coding the intensity and location of noxious visceral and somatic stimuli and for organizing the appropriate sequence of motor responses when multiple noxious stimuli are present.     

Spinal inhibitory effects of cardiopulmonary afferent inputs in monkeys: neuronal processing in high cervical segments

Noxious stimulation of spinal afferents inhibits primate spinothalamic tract (STT) neurons in segments distant from the region of afferent entry. Inhibitory effects of cardiopulmonary sympathetic afferent (CPSA) stimulation remain after C(1) transection but disappear with spinal transection between C(3) and C(7). We hypothesized that spinal inhibitory effects produced by CPSA stimulation are processed by neurons in C(1)-C(3) segments. One purpose of this study in anesthetized monkeys was to determine whether chemical activation of high cervical neurons reduced sacral STT cell responses to colorectal distension (CRD) and urinary bladder distension (UBD). First, effects and interactions of pelvic and cardiopulmonary visceral afferent inputs were determined in 10 monkeys on extracellular activity of sacral STT neurons recorded in deep dorsal horn. CRD and UBD increased activity in 95 and 91% of sacral STT neurons, respectively. CPSA and cardiopulmonary vagal stimulation decreased activity in 84 and 56% of STT neurons, respectively. CPSA stimulation decreased CRD-evoked activity in six of eight sacral STT neurons and decreased UBD-evoked activity in five of eight STT neurons tested. Excitatory amino acid application at C2 segment decreased CRD-evoked responses in 7 of 10 sacral STT neurons and decreased UBD-evoked responses in 9 of 12 STT neurons. The second purpose of this study was to examine responses of C(1)-C(3) descending propriospinal neurons to stimulation of cardiopulmonary afferent fibers. If C(1)-C(3) neurons process CPSA input to suppress STT transmission, then CPSA stimulation should excite C(1)-C(3) neurons with descending projections. Effects of thoracic vagus nerve stimulation also were examined. Vagal stimulation inhibits STT neurons in segments below C(3) but excites C(1)-C(3) STT neurons; we theorized that vagal inhibition of sensory transmission might relay in high cervical segments and, therefore, excite C(1)-C(3) descending propriospinal neurons. Extracellular discharge rate was recorded for C(1)-C(3) neurons antidromically activated from thoracic or lumbar spinal cord in 24 monkeys. CPSA stimulation increased activity of 16 of 45 neurons and inhibited one cell. Thoracic vagus stimulation increased activity of 20 of 43 neurons and inhibited one cell; stimulation of abdominal vagus fibers did not affect activity of six of six cells that were excited by thoracic vagal input. Mechanical stimulation of somatic fields excited 30 of 41 neurons tested. All neurons activated by visceral input received convergent somatic input from noxious pinch of somatic receptive fields that generally included the neck and upper body; 11 C(1)-C(3) propriospinal neurons did not respond to any afferent input examined. Results of these studies were consistent with the idea that modulation of spinal nociceptive transmission might involve neuronal connections in high cervical segments.     

Convergence of central respiratory and locomotor rhythms onto single neurons of the lateral reticular nucleus

We have analyzed the behavior of neurons of the lateral reticular nucleus (LRN) during fictive respiration and locomotion and found that some LRN neurons have both central respiratory and locomotor rhythms. Experiments were conducted on decrebrate, decerebellate, immobilized, and artificially ventilated cats, with the spinal cord transected at the lower thoracic cord. Fictive respiration and fictive forelimb locomotion were ascertained by monitoring activities from the phrenic nerve and forelimb extensor and flexor nerves, respectively. Fictive locomotion was evoked by electrical stimulation of the mesencephalic locomotor region (MRL) or sometimes occurred spontaneously. During fictive locomotion many LRN neurons fired in certain phases of the locomotion cycle; i.e., with respect to the nerve discharge of the ipsilateral forelimb they fired in either the extensor, flexor, extensor-flexor, or flexor-extensor phase. Firing of some LRN neurons was modulated synchronously with central respiratory rhythm. Neurons with inspiratory activity and those with expiratory activity were both found. More than half of these respiration-related LRN neurons had locomotor rhythm as well. The majority of the three types of LRN neurons, i.e., neurons with only locomotor rhythm, those with only respiratory rhythm, and those with both respiratory and locomotor rhythm, were antidromically activated by electrical stimulation of the ipsilateral inferior cerebellar peduncle. Electrical stimulation of the upper cervical cord showed that these LRN neurons, not only locomotion-related but also respiration-related neurons, received short latency inputs from the spinal cord. The LRN neurons studied were distributed widely in the LRN, relatively densely in the caudal two-thirds of the nucleus. No particular differences were detected between the three types of LRN neurons with respect to their location in the nucleus. These results indicate that the information about central respiratory and locomotor rhythms that is necessary for cerebellar control of the coordination between respiration and locomotion converges, at least partly, at the level of the LRN.     

Interactions between visceral and cutaneous nociception in the rat. I. Noxious cutaneous stimuli inhibit visceral nociceptive neurons and reflexes

1. Numerous studies have demonstrated that neural, behavioral, and reflex responses to a nociceptive test stimulus are inhibited by conditioning nociceptive stimuli; this inhibition has supraspinal, intraspinal, and segmental components. The general phenomenon is defined here as nocigenic inhibition. The present study of nocigenic inhibition documents that noxious cutaneous pinch and heat, used as conditioning stimuli, inhibit neuronal and reflex responses evoked by a noxious visceral stimulus, colorectal distension. 2. A total of 196 dorsal horn neurons were examined: 110 were short latency-abrupt (SL-A) neurons that were excited at short latency by colorectal distension and returned to baseline activity abruptly after termination of the distending stimulus, and 86 were short latency-sustained (SL-S) neurons that also were excited by colorectal distension at short latency, but demonstrated after-discharges for 4-240 s after termination of the distending stimulus. All SL-A and SL-S neurons studied had convergent cutaneous receptive fields. 3. The spontaneous activities of 100% of the 110 SL-A neurons tested were inhibited by greater than 25% by noxious pinch in sites distant from their convergent cutaneous receptive fields. In both anesthetized, intact, and spinalized rats, noxious conditioning pinch or noxious conditioning heat significantly reduced responses of SL-A neurons during noxious test colorectal distension. The magnitude of this nocigenic inhibition was graded with the intensity of the noxious conditioning stimulus. Noxious conditioning tail heating produced a parallel shift to the right in stimulus-response functions relating neuronal responses to the intensity of colorectal distension (20-100 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fluorescent double-label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat.

Following injections of WGA-HRP into either the spinal cord or periaqueductal gray, labeled neurons were observed bilaterally along the periphery of the lateral reticular nucleus (LRN) magnocellular division. The possibility that some of these neurons in the LRN provide collateral axonal branches to both the periaqueductal gray and the spinal cord was investigated in rats using a retrograde double-labeling method employing two different fluorescent tracers, True Blue and Nuclear Yellow. Following sequential injection of the two fluorescent axonal tracers into the spinal cord and periaqueductal gray in the same animal, a modest number of double-labeled neurons were observed bilaterally near the medial and dorsal perimeter of the magnocellular division of the LRN. The labeled neurons were distinctly multipolar in shape and measured approximately 15-18 mu in their greatest transverse diameter. No double-labeled neurons were observed in the parvocellular or subtrigeminal divisions of the LRN. Based upon these observations, it is suggested that collaterals of the LRN-spinal pathway provide feedback information to the periaqueductal gray that might then be used to modulate the participation of the latter cell group in a variety of pain processing and cardiovascular regulatory functions.     

Fluorescent double‐label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat

Following injections of WGA‐HRP into either the spinal cord or periaqueductal gray, labeled neurons were 7observed bilaterally along the periphery of the lateral reticular nucleus (LRN) magnocellular division. The possibility that some of these neurons in the LRN provide collateral axonal branches to both the periaqueductal gray and the spinal cord was investigated in rats using a retrograde double‐labeling method employing two different fluorescent tracers, True Blue and Nuclear Yellow. Following sequential injection of the two fluorescent axonal tracers into the spinal cord and periaqueductal gray in the same animal, a modest number of double‐labeled neurons were observed bilaterally near the medial and dorsal perimeter of the magnocellular division of the LRN. The labeled neurons were distinctly multipolar in shape and measured approximately 15–18 μ in their greatest transverse diameter. No double‐labeled neurons were observed in the parvocellular or subtrigeminal divisions of the LRN. Based upon these observations, it is suggested that collaterals of the LRN‐spinal pathway provide feedback information to the periaqueductal gray that might then be used to modulate the participation of the latter cell group in a variety of pain processing and cardiovascular regulatory functions. Anat Rec 256:91–98, 1999. © 1999 Wiley‐Liss, Inc.     

Expression of brain prolactin releasing peptide (PrRP) changes in the estrous cycle of female rats

The aim of this study was to determine whether spinal cord stimulation (SCS) modulates activity of lumbosacral spinal neurons receiving input from the urinary bladder. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms, 3-5 min, 90% motor threshold) was applied on the dorsal column of L2-L3 and C1-C2 segments and significantly reduced excitatory responses of 18/25 (72%) and 13/19 (68%) lumbosacral neurons to noxious urinary bladder distension (UBD, > or =1.0 ml, 20 s), respectively. SCS affected spinal neurons with either high- or low-threshold responses to UBD. These results suggested that SCS might have a potential therapeutic effect for patients with hypersensitivity and/or pain of cystitis and other urinary bladder disorders.     

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+     

Characterization of neurons responsive to noxious colorectal distension in the T13-L2 spinal cord of the rat

1. One-hundred thirty-two neurons responsive to colorectal distension in the dorsal horn of the T13-L2 spinal segments of 35 spinalized and 7 intact, deeply pentobarbital-sodium-anesthetized rats were characterized for convergent cutaneous receptive fields, long ascending projections and responses to the intra-arterial administration of the algesic peptide bradykinin. All but 9 neurons had an identifiable excitatory cutaneous receptive field; all receptive fields were located on the lower abdomen, flank, and dorsal body surface. Electrical stimulation in the cutaneous fields of 28 neurons demonstrated that neurons responsive to colorectal distension receive afferent information carried by A- and C-fibers. Stimulus-response functions (SRFs) of 52 neurons excited by graded colorectal distension (20-100 mmHg, 20 s) were monotonic and accelerating, allowing extrapolation of threshold distending pressures to neuronal response. Neurons were subdivided into four classes based upon their response to an 80-mmHg, 20-s colorectal distension search stimulus. 2. Short-latency abrupt [SL-A] neurons (spinalized, n = 46; intact, n = 9) were excited at short latency; activity abruptly returned to base line on termination of distension. Six of 9 neurons in intact rats had long ascending projections as demonstrated by antidromic invasion from the contralateral, ventrolateral caudal medulla. Responses of SL-A neurons to colorectal distension were significantly greater in spinalized than in intact rats. Fifty-three of 55 SL-A neurons had convergent excitatory cutaneous receptive fields and most were responsive to both noxious and nonnoxious stimuli. Ten of 13 neurons tested were excited by intra-arterial bradykinin. The threshold distending pressure, determined from the SRFs of 29 neurons in both the spinalized and intact states, extrapolated to near 0 mmHg. 3. Short-latency sustained (SL-S) neurons (spinalized, n = 31; intact, n = 11) were also excited at short latency in response to colorectal distension, but responses were sustained for 4-50 s following termination of the distending stimulus. Nine of 11 SL-S neurons in intact rats had long ascending projections. All 42 SL-S neurons were spontaneously active and 41 of 42 had convergent excitatory cutaneous receptive fields, excited exclusively by noxious stimuli (n = 29) or excited by both noxious and nonnoxious stimuli (n = 12). Responses to colorectal distension and spontaneous activity were significantly greater in spinalized rats. Twelve of 12 neurons tested were excited by intra-arterial bradykinin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses and afferent pathways of C1-C2 spinal neurons to cervical and thoracic esophageal stimulation in rats

Because vagal and sympathetic inputs activate upper cervical spinal neurons, we hypothesized that stimulation of the esophagus would activate C(1)-C(2) neurons. This study examined responses of C(1)-C(2) spinal neurons to cervical and thoracic esophageal distension (CED, TED) and afferent pathways for CED and TED inputs to C(1)-C(2) spinal neurons. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital-anesthetized male rats. Graded CED or TED was produced by water inflation (0.1-0.5 ml) of a latex balloon. CED changed activity of 48/219 (22%) neurons; 34 were excited (E), 12 were inhibited (I), and 2 were E-I. CED elicited responses for 18/18 neurons tested after ipsilateral cervical vagotomy, for 12/14 neurons tested after bilateral vagotomy and for 9/11 neurons tested after bilateral vagotomy and C(6)-C(7) spinal cord transection. TED changed activity of 31/190 (16%) neurons (28E, 3 I). Ipsilateral cervical vagotomy abolished TED-evoked responses of 5/12 neurons. Bilateral vagotomy eliminated responses of 2/4 neurons tested, and C(6)-C(7) spinal transection plus bilateral vagotomy eliminated responses of 2/2 neurons. Thus inputs from CED to C(1)-C(2) neurons most likely entered upper cervical dorsal roots, whereas inputs from TED were dependent on vagal pathways and/or sympathetic afferent pathways that entered the thoracic dorsal roots. These results supported a concept that C(1)-C(2) spinal neurons play a role in integrating visceral information from cervical and thoracic esophagus.