Spinal Neuronal Responses to Urinary Bladder Stimulation in Rats With Corticosterone or Aldosterone Onto the Amygdala

2003 ◽  
Vol 90 (4) ◽  
pp. 2180-2189 ◽  
Author(s):  
Chao Qin ◽  
Beverley Greenwood-Van Meerveld ◽  
Robert D. Foreman

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.

2003 ◽  
Vol 90 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Chao Qin ◽  
Beverley Greenwood-Van Meerveld ◽  
Robert D. Foreman

Stereotaxic delivery of corticosterone onto the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. Since corticosterone activates both the mineralocorticoid (MR) and glucocorticoid (GR) receptors, the aim of this study was to determine the importance of MRs in the regulation of colorectal hypersensitivity through the use of aldosterone that preferentially binds to MRs. Fischer-344 rats received either aldosterone ( n = 18)- or cholesterol (control, n = 18)-containing micropellets bilaterally placed stereotaxically on the dorsal margin of the amygdala. After 1 wk, colorectal sensitivity to distension (30 mmHg) was measured in a subgroup of rats ( n = 8/group). In other rats ( n = 10/group), extracellular potentials of single L6–S1 spinal neurons in response to colorectal distension (CRD; 10–80 mmHg) were recorded. In aldosterone-implanted rats, CRD produced a greater visceromotor behavioral response compared with cholesterol controls (19 ± 0.5 vs. 11.5 ± 2.7; P < 0.01). A total of 68/182 (37%) and 56/167 (34%) of spinal neurons responded to noxious CRD in aldosterone-implanted and control groups, respectively. A total of 36/42 (86%) neurons excited by CRD had spontaneous activity in aldosterone-implanted groups compared with control (19/33, 58%, P < 0.01). Neurons with low thresholds for excitatory responses to CRD were seen more frequently in aldosterone-implanted rats than those in the control group (35/39 vs. 18/31, P < 0.05). Maximal excitatory responses of neurons to CRD in aldosterone-implanted rats were significantly greater (23.9 ± 2.2 vs. 16.4 ± 2.0 imp/s, P < 0.05), and the durations were longer (34.3 ± 2.7 vs. 24.9 ± 1.4 s, P < 0.05) than those in control group. Finally, a greater number of neurons had wide dynamic range responses to somatic stimulation in aldosterone-treated rats compared with cholesterol controls. Our findings suggest that, in the amygdala, MR receptor–mediated mechanisms are likely involved in descending pathways onto lumbosacral spinal neurons that induce colorectal hypersensitivity to luminal distension.


1993 ◽  
Vol 265 (6) ◽  
pp. R1291-R1303
Author(s):  
A. Standish ◽  
M. A. Vizzard ◽  
W. S. Ammons

Experiments were conducted in anesthetized cats to determine if spinal neuronal responses to activation of renal receptors are tonically modulated by descending spinal pathways. Eighty-seven thoracolumbar spinal neurons with renal and somatic input were tested for responses to occlusion of the renal vein, renal artery, and ureter before, during, and after cooling the spinal cord rostral to the recording site. Cooling increased the number of neurons that responded as well as the magnitude of the responses to renal vein (RVO), renal artery (RAO), and ureteral occlusion (UO). RVO increased cell activity of 21 neurons from 12.5 +/- 2.7 to 31.7 +/- 6.0 spikes/s during cooling. UO increased cell activity of 24 neurons from 9.0 +/- 2.1 before cooling to 25.0 +/- 4.9 spikes/s during cooling. Cold block increased the magnitude of both types of responses to RAO that were due to mechanical deformation of the renal artery and prolonged renal ischemia. These data show that the majority of spinal neuronal responses to renal receptor stimulation are modulated by tonic inhibitory influences. Thus these results provide a mechanism by which the brain may control spinal circuitry that underlies reflexes of renal origin.


1990 ◽  
Vol 258 (1) ◽  
pp. R10-R20 ◽  
Author(s):  
S. F. Hobbs ◽  
U. T. Oh ◽  
T. J. Brennan ◽  
M. J. Chandler ◽  
K. S. Kim ◽  
...  

Upper thoracic spinal neurons are primarily excited by cardiopulmonary spinal afferent input but are excited and inhibited by splanchnic afferent input. These data suggest that the greater the number of segments between a spinal neuron and spinal afferent input the greater the probability that the afferent input will inhibit the spinal neuron. Based on this idea we hypothesized that visceral (urinary bladder) and somatic (hindlimb) afferent input would inhibit upper thoracic spinal neurons. To test this hypothesis the activities of 69 spinal and 27 spinoreticular tract neurons in 45 alpha-chloralose-anesthetized cats were studied. Only neurons excited by both visceral and somatic thoracic afferent input were studied. Urinary bladder distension (UBD) inhibited 48 (50%), excited 6 (6%), and did not affect 41 (43%) of these neurons. Also, UBD inhibited the excitatory responses of these cells to noxious visceral and somatic stimuli. Hindlimb pinch also inhibited greater than 50% of the neurons. These data indicate that visceral and somatic afferent input to the lumbosacral spinal cord inhibits the activity of upper thoracic neurons. This inhibitory effect may play a role in localization of sensory and motor responses to noxious stimuli.


1996 ◽  
Vol 75 (4) ◽  
pp. 1411-1431 ◽  
Author(s):  
K. A. Davis ◽  
J. Ding ◽  
T. E. Benson ◽  
H. F. Voigt

1. The electrophysiological responses of single units in the dorsal cochlear nucleus of unanesthetized decerebrate Mongolian gerbil (Meriones unguiculatus) were recorded. Units were classified according to the response map scheme of Evans and Nelson as modified by Young and Brownell, Young and Voigt, and Shofner and Young. Type II units have a V-shaped excitatory response map similar to typical auditory nerve tuning curves but little or no spontaneous activity (SpAc < 2.5 spikes/s) and little or no response to noise. Type I/III units also have a V-shaped excitatory map and SpAc < 2.5 spikes/s, but have an excitatory response to noise. Type III units have a V-shaped excitatory map with inhibitory sidebands, SpAc > 2.5 spikes/s, and an excitatory response to noise. Type IV-T units typically also have a V-shaped excitatory map with inhibitory sidebands, but have a highly nonmonotonic rate versus level response to best frequency (BF) tones like type IV units, SpAc > 2.5 spikes/s, and an excitatory response to noise. Type IV units have a predominantly inhibitory response map above an island of excitation of BF, SpAc > 2.5 spikes/s, and an excitatory response to noise. We present results for 133 units recorded with glass micropipette electrodes. The purpose of this study was to establish a normative response map data base in this species for ongoing structure/function and correlation studies. 2. The major types of units (type II, type I/III, type III, type IV-T, and type IV) found in decerebrate cat are found in decerebrate gerbil. However, the percentage of type II (7.5%) and type IV (11.3%) units encountered are smaller and the percentage of type III (62.4%) units is larger in decerebrate gerbil than in decerebrate cat. In comparison, Shofner and Young found 18.5% type II units, 30.6% type IV units, and 23.1% type III units using metal electrodes. 3. Two new unit subtypes are described in gerbil: type III-i and type IV-i units. Type III-i units are similar to type III units except that type III-i units are inhibited by low levels of noise and excited by high levels of noise whereas type III units have strictly excitatory responses to noise. Type IV-i units are similar to type IV units except that type IV-i units are excited by low levels of noise and become inhibited by high levels of noise whereas type IV units have strictly excitatory responses to noise. Type III-i units are approximately 30% of the type III population and type IV-i units are approximately 50% of the type IV population. 4. On the basis of the paucity of classic type II units and the reciprocal responses to broadband noise of type III-i and type IV-i units, we postulate that some gerbil type III-i units are the same cell type and have similar synaptic connections as cat type II units. 5. Type II and type I/III units are distinguished from one another on the basis of both their relative noise response, rho, and the normalized slope of the BF tone rate versus level functions beyond the first maximum. Previously, type II units were defined to be those nonspontaneously active units with rho values < 0.3 where rho is defined as the ratio of the maximum noise response minus spontaneous rate to the maximum BF tone response minus spontaneous rate. In the gerbil, the average rho value for type II units is 0.25, although a few values are > 0.3, and the rate-level curves are consistently nonmonotonic with normalized slopes steeper than than -0.007/dB. The average rho value for type I/III units is 0.54, although a few values are < 0.3, and the rate-level curves tend to saturate with slopes shallower than -0.006/dB. In general, the response properties of type II units recorded in gerbil are similar to those recorded in decerebrate cat. 6. In comparison to decerebrate cat, the lower percentage of type IV units recorded in decerebrate gerbil may be due to a species difference (a reduced number of type II units in gerbil) or an electrode bias.


2006 ◽  
Vol 291 (6) ◽  
pp. R1700-R1707 ◽  
Author(s):  
Chao Qin ◽  
Jay P. Farber ◽  
Kenneth E. Miller ◽  
Robert D. Foreman

The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activate cardiac nociceptive receptors, a catheter was placed in the pericardial sac to administer various chemicals: bradykinin (BK; 10 μg/ml, 0.2 ml), capsaicin (CAP, 10 μg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing adenosine 10−3 M, BK, serotonin, histamine, and PGE2, 10−5 M for each. Spinal neurons that responded to intrapericardial BK and/or CAP were used in this study. Results showed that 81% (35/43) of the neurons had excitatory responses to both intrapericardial BK and CAP, and the remainder responded to either BK or CAP. Intrapericardial resiniferatoxin (RTX) (0.2 μg/ml, 0.2 ml, 1 min), which desensitizes TRPV1-containing nerve endings, abolished excitatory responses to both BK ( n = 8) and CAP ( n = 7), and to AC ( n = 5) but not to somatic stimuli. Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial capsazepine had no significant effect on excitatory responses to AC in 3/3 neurons. These data indicated that intrapericardial BK-initiated spinal neuronal responses were linked to cardiac TRPV1-containing afferent fibers, but were not dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated through CAP-sensitive afferent fibers innervating the heart.


2000 ◽  
Vol 83 (3) ◽  
pp. 1224-1242 ◽  
Author(s):  
Alan M. Brichta ◽  
Jay M. Goldberg

Multivariate statistical formulas were used to infer the morphological type and longitudinal position of extracellularly recorded afferents. Efferent fibers were stimulated electrically in the nerve branch interconnecting the anterior and posterior VIIIth nerves. Responses of bouton (B) units depended on their inferred position: BP units (near the planum semilunatum) showed small excitatory responses; BT units (near the torus) were inhibited; BM units (in an intermediate position) had a mixed response, including an initial inhibition and a delayed excitation. Calyx-bearing (CD-high) units with an appreciable background discharge showed large per-train excitatory responses followed by smaller post-train responses that could outlast the shock train by 100 s. Excitatory responses were smaller in calyx-bearing (CD-low) units having little or no background activity than in CD-high units. Excitatory response-intensity functions, derived from the discharge during 2-s angular-velocity ramps varying in intensity, were fit by empirical functions that gave estimates of the maximal response ( r MAX), a threshold velocity ( v T), and the velocity producing a half-maximal response ( v 1/2). Linear gain is equal to r MAX/ v S, v S = v 1/2 − v T. v S provides a measure of the velocity range over which the response is nearly linear. For B units, r MAX declines by as much as twofold over the 2-s ramp, whereas for CD units, r MAXincreases by 15% during the same time period. At the end of the ramp, r MAX is on average twice as high in CD as in B units. Thresholds are negligible in most spontaneously active units, including almost all B and CD-high units. Silent CD-low units typically have thresholds of 10–100 deg/s. BT units have very high linear gains and v S < 10 deg/s. Linear gains are considerably lower in BP units and v S> 150 deg/s. CD-high units have intermediate gains and near 100 deg/s v S values. CD-low units have low gains and v S values ranging from 150 to more than 300 deg/s. The results suggest that BT units are designed to measure the small head movements involved in postural control, whereas BP and CD units are more appropriate for monitoring large volitional head movements. The former units are silenced by efferent activation, whereas the latter units are excited. This suggests that the efferent system switches the turtle posterior crista from a “postural” to a “volitional” mode.


1983 ◽  
Vol 245 (3) ◽  
pp. R311-R320 ◽  
Author(s):  
R. Schondorf ◽  
W. Laskey ◽  
C. Polosa

The aim of the present study was to evaluate the organization of neural circuitry responsible for the intersegmental transmission of input from urinary bladder afferents to sympathetic preganglionic neurons (SPNs). The electrical activity of SPNs was recorded from axons of the cervical sympathetic trunk in anesthetized central nervous system (CNS)-intact and in unanesthetized midcollicular-decerebrate or acute C1 spinal cats. In all three preparations, tonically active SPNs were excited or inhibited by 1) electrical stimulation of myelinated afferents of the pelvic or hypogastric nerve, both of which contain bladder afferents, and 2) spontaneous contraction or distension of the urinary bladder. The SPN responses to bladder distension were abolished by pelvic nerve section. A comparison of responses of SPNs in CNS-intact and acute spinal animals to electrical stimulation of pelvic nerve afferents suggests that both propriospinal and supraspinal circuits are involved in the intersegmental transmission of input from bladder afferents to SPNs.


1999 ◽  
Vol 277 (3) ◽  
pp. R786-R794 ◽  
Author(s):  
Chen-Li Cheng ◽  
Jiang-Chuan Liu ◽  
Sun-Yran Chang ◽  
Cheng-Ping Ma ◽  
William C. de Groat

The effect of capsaicin (10–80 mg/kg sc) on reflex activity of the urinary bladder was examined in anesthetized normal as well as anesthetized and awake chronic spinal cord-injured (SCI) cats. In normal cats, capsaicin elicited a transient increase in the frequency of isovolumetric bladder contractions and reduced the volume threshold for inducing micturition, but did not depress the amplitude of bladder contractions or the reflex firing on bladder nerves. In anesthetized SCI cats, capsaicin depressed reflex bladder activity and firing on bladder nerves. In awake SCI cats, capsaicin initially decreased the volume threshold for inducing micturition; however, after a delay of 3–6 h the volume threshold increased and intravesical voiding pressure decreased. This effect persisted for 4–12 days. It is concluded that capsaicin-sensitive C fiber bladder afferents are not involved in initiating reflex micturition in normal cats, but play an essential role in triggering automatic micturition in chronic SCI cats. The results are consistent with the clinical data indicating that C fiber bladder afferents contribute to bladder hyperactivity and incontinence in patients with neurogenic bladder dysfunction.


2002 ◽  
Vol 96 (6) ◽  
pp. 1410-1419 ◽  
Author(s):  
Pablo J. Castroman ◽  
Timothy J. Ness

Background The effect of ketamine as a treatment of visceral pain is not known. The current study investigated the effect of ketamine on spinal dorsal horn neurons excited by urinary bladder distension (UBD). The effect of other clinically available N-methyl-D-aspartate receptor antagonists on these responses was also studied. Methods Extracellular recordings of neurons located in the L6-S2 spinal dorsal horn of cervical spinal cord-transected, decerebrate female rats were obtained. Cutaneous receptive fields of neuronal units excited by UBD were characterized for responses to segmental noxious and nonnoxious stimuli. Nonsegmental noxious stimuli were also applied, and neurons were classified as type I (inhibited) and type II (noninhibited) by the stimulus. The effect of intravenous ketamine (1, 3, and 10 mg/kg), dextromethorphan (5 mg/kg), and memantine (16 mg/kg) on neuronal responses of these units was measured. Results Spontaneous and evoked neuronal activity to UBD was reduced in a dose-dependent fashion by ketamine. Responses to nonnoxious cutaneous stimuli were also significantly reduced after treatment. Dextromethorphan inhibited neuronal activity evoked by UBD in type I neurons. A similar selective effect of treatment on type I versus type II neurons was observed after intravenous ketamine and memantine. Conclusions Intravenous ketamine produces dose-dependent inhibition of the spinal cord neuronal responses evoked by UBD. All three N-methyl-D-aspartate receptor antagonists showed selective effects on spinal cord neurons subject to counterirritation. This neurophysiologic evidence supports a spinally mediated analgesic effect of ketamine in this model of urinary bladder nociception, an effect likely caused by N-methyl-D-aspartate receptor antagonism.


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