Evidence for two populations of rat spinal dorsal horn neurons excited by urinary bladder distension

Spinal L6-S2 dorsal horn neurons of cervical spinal cord-transected, decerebrate female rats were characterized using urinary bladder distension (UBD) as a visceral stimulus. Constant pressure, phasic, graded (20-80 mm Hg, 20 s) air UBD was delivered via a transurethral catether and extracellular single-unit recordings obtained from all neurons excited by UBD. Responses to graded UBD and noxious/non-noxious cutaneous stimuli were determined in 258 neurons which could be stratified into two groups based on their effect of a counterirritation stimulus: Type I neurons (n=112) were inhibited by noxious pinch presented in a non-segmental field; Type II neurons (n=146) were not similarly inhibited. Both Types of neurons were identified in both superficial and deep recording sites and demonstrated graded responses to graded UBD. All UBD-excited neurons had convergent cutaneous receptive fields (RFs) excited by non-noxious and/or noxious stimuli. As a group, Type I neurons had a period of decreased activity following termination of the distending stimulus whereas Type II neurons typically had a sustained afterdischarge. UBD-evoked activity in Type II neurons was inhibited more than similar activity in Type I neurons by both intravenous morphine and lidocaine. These results support the assertion that at least two different populations of spinal dorsal horn neurons exist which encode for a stimulus of urinary bladder distension. These populations are an analogue to previously characterized, similar neuronal populations excited by colorectal distension and suggest that they are representative of the overall phenomenon of visceral sensory processing, a component of which is nociception.     

Effects of urinary bladder distension on activity of T3-T4 spinal neurons receiving cardiac and somatic noxious inputs in rats

The aims of this study were to examine effects of urinary bladder distension (UBD) on T(3)-T(4) spinal neurons receiving cardiac and somatic noxious inputs and to determine the pathway involved in transmitting urinary bladder inputs to thoracic spinal segments. Extracellular potentials of single T(3)-T(4) neurons were recorded in pentobarbital anesthetized male rats. Either bradykinin solution (10(-5) M) or an allogenic mixture (adenosine 10(-3) M, bradykinin, histamine, serotonin, prostaglandin E2 10(-5) M each) was administered intrapericardially. UBD was produced by saline inflation (0.5-2.0 ml, 20 s). Of 487 neurons tested for responses to UBD, 70 were inhibited and 37 were excited. Seventy-six out of 336 neurons received convergent input from UBD and heart; 69/76 viscerovisceral convergent neurons had somatic fields. Spinal transection at rostral C(1) abolished UBD inhibition in 5/9 neurons; whereas transections at L(1)-L(2) abolished UBD inhibition in 3/3 cells tested. Results showed that T(3)-T(4) spinal neurons processing cardiac and somatic nociceptive information were primarily inhibited by input from the urinary bladder through either supraspinal structures or direct intraspinal pathways.     

Neonatal cystitis‐induced colonic hypersensitivity in adult rats: a model of viscero‐visceral convergence

Background The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Methods Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days [(postnatal (PN) days 14–16)]. The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissues. CRD‐ or urinary bladder distension (UBD)‐sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N‐methyl‐d ‐aspartic acid (NMDA)‐NR1 subunit in the lumbo‐sacral (L6‐S1) spinal cord was examined using Western blot. Key Results The VMR to CRD (≥10 mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD‐sensitive PNAs from the zymosan‐treated rats was significantly higher than the saline‐treated control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (P > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan‐treated rats compared with saline‐treated rats (P < 0.05). Conclusions & Inferences Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD‐sensitive PNAs. Neonatal cystitis does result in overexpression of spinal NR1 subunit in adult rats.     

Afferent pathways and responses of T3-T4 spinal neurons to cervical and thoracic esophageal distensions in rats

The purposes of this study were to (1) compare responses of T(3)-T(4) spinal neurons to thoracic and cervical esophageal distension (TED, CED) and (2) determine afferent pathways for esophageal input to these neurons. Extracellular potentials of single superficial and deeper T(3)-T(4) neurons were recorded in pentobarbital anesthetized male rats. Graded TED or CED was produced by water inflation (0.1-0.5 ml) of a latex balloon. TED changed activity of 121/432 (28%) neurons (114 were excited); CED activated 69/269 (26%) neurons (56 were excited). Of 151 neurons that were tested for responses to both TED and CED, 40 (26%) neurons responded to both TED and CED. Mean duration of excitatory responses in convergent neurons to TED was significantly longer than the duration of responses to CED (31.4+/-2.8 vs. 25.4+/-1.0 s, n=34, P<0.05). A total of 105 out of 121 (87%) and 66 out of 69 (96%) neurons responsive to TED and CED had somatic fields. Spinal transection at rostral C(1) and at C(7)-C(8) indicated that excitatory responses to TED resulted from activation of afferent input that entered thoracic spinal segments; whereas, excitatory responses to CED resulted from afferent inputs entering cervical or thoracic spinal segments. These data showed that the upper thoracic spinal cord received sensory information from the esophagus through cervical and/or thoracic spinal visceral afferent pathways.     

Differential effects of urinary bladder distension on high cervical projection neurons in primates

Projection neurons located in high cervical segments of primates are generally excited instead of inhibited by cardiopulmonary spinal inputs, which enter thoracic dorsal roots. Thus, high cervical neurons with axons that either ascend to the thalamus or descend to thoracolumbar spinal segments can process and transmit excitatory cardiac information. The purpose of this study was to determine whether the excitatory effects observed to cardiopulmonary afferent stimulation are a universal response in high cervical projection neurons to spinal visceral inputs. Urinary bladder distension (UBD) was used to stimulate visceral afferent inputs that enter lumbosacral dorsal roots. Effects were determined on extracellular activity of either spinothalamic tract (STT) neurons or descending propriospinal neurons that were recorded in high cervical segments of anesthetized monkeys. Results showed that 17/34 STT neurons were inhibited by UBD and 3/34 STT neurons were excited. Widespread visceral inputs, therefore, can excite high cervical STT neurons but the majority of responsive STT neurons were inhibited by UBD. Effects of UBD on high cervical descending propriospinal neurons were significantly different from responses in STT neurons. Extracellular activity of fewer propriospinal neurons was affected by UBD and responses were more variable; 3/26 neurons were inhibited, 5/26 neurons were excited and one neuron was excited/inhibited by UBD. These results showed that the generally excitatory responses of high cervical projection neurons to cardiopulmonary inputs were not duplicated by stimulation of sensory input from the urinary bladder. Furthermore, results of this study indicated that effects of sensory inputs on spinal neurons might vary depending on axonal projections of the neurons examined.     

Afferent pathway and neuromodulation of superficial and deeper thoracic spinal neurons receiving noxious pulmonary inputs in rats

The occurrence of vagally mediated afferent signaling by lung irritants is well known. However, spinal visceral afferent pathways also might be relevant to pulmonary irritation. In the present study, responses and modulation of superficial and deep T3 spinal neurons were examined using inhaled ammonia, and the peripheral afferent fibers were also characterized in part. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Ammonia vapor (0.5, 1.0, 2.0 ml) was injected into the inspiratory line of the ventilator for 20 s. Inhaled ammonia (IA, 1.0 ml) excited 5/6 neurons and inhibited one spinal neuron recorded in superficial laminae, whereas deeper neurons responded with excitatory (E, n = 20), inhibitory (I, n = 4) or biphasic patterns (6 E-I, 3 I-E). Electrical and chemical stimulation of C1-C2 spinal neurons primarily suppressed T3 neuronal responses to IA. Resiniferatoxin (2 microg/kg, i.v.), which desensitizes afferent fibers containing transient receptor potential vanilloid receptor-1 (TRPV-1), abolished excitatory responses of 8/8 neurons to IA. Bilateral cervical vagotomy did not affect IA responses in 5 superficial neurons while 7 deeper neurons showed variable responses. 82% (32/39) of the spinal neurons responding to IA also received convergent noxious inputs from somatic fields in the chest and back areas. These results suggested that superficial and deeper spinal neuronal activation by inhaled ammonia mainly depended upon pulmonary sympathetic afferent fibers expressing TRPV-1. Additionally, C1-C2 spinal neurons, supraspinal sites and vagal afferents modulated the thoracic spinal neuronal responses to lower airway irritation.     

Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension.

The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex.     

Electrical stimulation of thalamic Nucleus Submedius inhibits responses of spinal dorsal horn neurons to colorectal distension in the rat

In 78 halothane-anesthetized rats, we characterized the responses of single neurons in the dorsal horn of L(6)-S(1) spinal segments to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of focal electrical stimulation of Nucleus Submedius (Sm) on these responses using standard extracellular microelectrode recording techniques. A total of 102 neurons were isolated on the basis of spontaneous activity. Eighty (78%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. Neurons showed graded responses to graded CRD pressures (20-100 mmHg), with maximum excitation or inhibition occurring at 100 mmHg. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 73 of the spinal dorsal horn neurons isolated. Fifty-seven (78%) of these neurons (46 CRD-responsive and 11 CRD-nonresponsive) had cutaneous receptive fields, of which 35 (61%) were small and ipsilateral, 14 (25%) were large and ipsilateral, 7 (12%) were large or small and bilateral, and 1 (2%) was small and contralateral. Sixty-one percent of these neurons responded to both noxious and innocuous cutaneous stimulation, 35% responded only to noxious stimulation, and 4% responded only to innocuous stimulation. Electrical stimulation (50-300 microA) of the contralateral Sm produced intensity-dependent attenuation of the CRD-evoked activities of most neurons (18/28 of CRD-excited and 7/12 of CRD-inhibited) tested. Sm stimulation produced facilitation of CRD responses of only one neuron (CRD-inhibited). Sm stimulation had no effects on spontaneous activity. These data indicate that Sm may be involved in the descending inhibitory modulation of visceral nociception at the spinal level.     

Effects of electrical stimulation of thalamic nucleus submedius and periaqueductal gray on the visceral nociceptive responses of spinal dorsal horn neurons in the rat

Electrical stimulation of the nucleus submedius (Sm) has been shown to suppress the viscerosomatic reflex (VSR), which is evoked by colorectal distension (CRD). We have examined the effects of focal electrical stimulation (0.3 ms, 50 Hz, 100 microA, 10 s) of the Sm and the periaqueductal gray (PAG) on the excitatory responses evoked by CRD in spinal dorsal horn neurons within the L6-S1 region in the urethane-anesthetized Wistar rats. Extracellular recordings were made from 32 spinal excitatory CRD responses. All of these neurons were convergent neurons with cutaneous receptive fields. The majority of the neurons (27/32) were wide dynamic range (WDR) neurons (responding to noxious and non-noxious cutaneous stimuli) while the remaining five neurons were nociceptive specific (NS) neurons (responding only to noxious cutaneous stimuli). The effects of electrical stimulation applied to 28 sites within the Sm were assessed for spinal neurons. Electrical stimulation in seven sites within the Sm (25%) inhibited the CRD excitatory response of dorsal horn neurons, while in two sites (7%) the same stimulation yielded facilitation. Electrical stimulation in the majority of the sites in the Sm (19/28, 68%) did not affect spinal excitatory CRD responses. On the other hand, electrical stimulation of the PAG clearly inhibited 20 of 22 (90%) CRD excitatory responses. These results suggest that the majority of Sm neurons may suppress VSR activity at a supraspinal reflex center rather than via a descending inhibition of spinal visceral nociceptive transmission, as is the case for the PAG.     

Modulation of visceral nociceptive responses of rat spinal dorsal horn neurons by sympathectomy

We determined whether sympathectomy modulates visceral nociception under physiological or inflammatory conditions. Recordings of sacral spinal dorsal horn neurons with sustained responses were performed in pentobarbitone-anesthetized rats. Graded colorectal distension (CRD, 20-100 mmHg) was used as a visceral nociceptive stimulus. Inflammation was induced by intracolonic instillation of turpentine (25%). Sympathectomy was produced by administering 6-hydroxydopamine. Inflammation produced an increase in the CRD-evoked responses. The CRD-evoked responses were attenuated following sympathectomy both under control and inflammatory conditions. These changes in the CRD-evoked responses were associated with corresponding changes in spontaneous discharge rate. The convergent input evoked by noxious pinch of the skin was not changed by any of the experimental conditions. The results indicate that sympathectomy attenuates visceral nociceptive responses and spontaneous activity of sacral spinal cord neurons, without effect on convergent cutaneous inputs, both under physiological and inflammatory conditions.     

Chemical activation of cardiac receptors affects activity of superficial and deeper T3-T4 spinal neurons in rats

The purposes of this study were to examine responses of superficial (depth <300 microm) and deeper thoracic spinal neurons to chemical stimulation of cardiac afferents and effects of descending influences on these neurons. Extracellular potentials of single T(3)-T(4) neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml of a mixture of algogenic chemicals that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, prostaglandin E(2) (10(-5) M). Fifteen of 55 (27%) superficial neurons responsive to intrapericardial chemicals were compared to 80/169 (47%) deeper neurons. All 15 superficial neurons that responded to cardiac afferents were excited (E), whereas 66 deeper neurons were excited, ten were inhibited and four showed excitation-inhibition. Spontaneous activity of superficial neurons with short-lasting excitatory responses was significantly lower than that of deeper neurons (P<0.05). Somatic receptive fields on chest, axilla, arm and upper back areas were found for 77/95 (81%) neurons that responded to intrapericardial chemicals. The proportion of somatic field properties and their sizes in superficial neurons were similar to deeper neurons. After cervical spinal transection, both spontaneous activity and responses to chemical stimulation of cardiac afferents significantly increased in six out of six neurons excited by intrapericardial injections. Results showed that chemical stimulation of cardiac afferents excited superficial T(3)-T(4) spinal neurons, whereas deeper neurons exhibited multiple patterns of responses. Some characteristics of subgroups of superficial neurons were quantitatively different from deeper neurons. Thoracic spinal neurons processing cardiac nociceptive information were under tonic descending inhibition.     

The effect of morphine on responses of nucleus ventroposterolateralis neurons to colorectal distension in the rat

In 71 halothane-anesthetized rats, we characterized the responses of single neurons in the nucleus ventroposterolateralis (VPL) of the thalamus to a noxious visceral stimulus (colorectal balloon distension; CRD) and studied the effects of intravenous morphine on these responses using standard extracellular microelectrode recording techniques. One hundred nine neurons were isolated on the basis of spontaneous activity. Sixty-four (59%) responded to CRD, of which 52 (81 %) had excitatory and 12 (19%) had inhibitory responses. Neurons showed graded responses to graded CRD pressures (20-100 mmHg), with maximum excitation or inhibition occurring at 80 mmHg. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 95 of the VPL neurons isolated. Eighty-three of these neurons (48 CRD responsive and 35 CRD nonresponsive) (87%) had cutaneous receptive fields, of which 96% were small and contralateral and 4% were large and contralateral or bilateral. Ninety-four percent of these neurons responded to both noxious and innocuous cutaneous stimulation, and 6% responded to only noxious stimulation. No neurons responded solely to innocuous stimulation. Cumulative doses of morphine (0.125, 0.25, 0.5, 1, and 2 mg/kg, i.v) produced statistically significant dose-dependent attenuation of neuronal responses to CRD. Naloxone (0.4 mg/ kg, i.v.) reversed the effects of morphine. Morphine and naloxone had no significant effects on spontaneous activity. These data support the involvement of VPL neurons in visceral nociception and are consistent with a role of VPL in sensory-discriminative aspects of nociception.     

The effect of morphine on responses of ventrolateral orbital cortex (VLO) neurons to colorectal distension in the rat

In 49 halothane-anesthetized rats, we characterized the responses of single neurons in the ventrolateral orbital cortex (VLO) to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine on these responses using standard extracellular microelectrode recording techniques. One hundred and four neurons were isolated on the basis of spontaneous activity. Fifty-seven (55%) responded to CRD, of which 32% had excitatory and 68% had inhibitory responses. Neurons showed tendencies toward graded responses to graded CRD pressures (20–100 mmHg), with maximum excitation or inhibition occurring at 80 or 100 mmHg, respectively. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 80 of the VLO neurons isolated. Thirty-three (41%) of these neurons (21 CRD-responsive and 12 CRD-nonresponsive) had cutaneous receptive fields, of which 79% were large and bilateral, 18% were small and bilateral, 3% were small and ipsilateral. Ninety-four percent of these neurons responded only to noxious cutaneous stimulation, 6% responded to both noxious and innocuous stimulation. No neurons responded solely to innocuous stimulation. Cumulative doses of morphine (0.0625, 0.125 and 0.25 mg/kg i.v.) produced statistically significant dose-dependent attenuation of neuronal responses to CRD. Naloxone (0.4 mg/kg i.v.) reversed the effects of morphine. Morphine and naloxone had no significant effects on spontaneous activity. These data support the involvement of VLO neurons in visceral nociception.     

Responses and afferent pathways of C(1)-C(2) spinal neurons to gastric distension in rats

Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1). the responses of C(1)-C(2) spinal neurons to gastric distension and (2). the relative contribution of vagal and spinal visceral afferent pathways for transmission of gastric input to the upper cervical spinal cord. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital anesthetized male rats. Graded gastric distension (20-80 mm Hg) was produced by air inflation of a latex balloon surgically placed in the stomach. Sixteen percent of the neurons (32/198) responded to gastric distension; 17 neurons were excited and 15 neurons were inhibited by gastric distension. Spontaneous activity of neurons with inhibitory responses was higher than those neurons with excitatory responses (18.1+/-2.7 vs. 3.8+/-1.7 impulses s(-1), p<0.001). Twenty-eight of thirty-two (87.5%) neurons responded to mechanical stimulation of somatic fields on head, neck, ears or shoulder. Most lesion sites of neurons with excitatory responses were found in laminae V, VII; however, neurons with inhibitory responses were in laminae III, IV. Bilateral cervical vagotomy abolished responses of 4/8 neurons tested. Spinal transection at C(6)-C(7) abolished responses of the other four neurons that still responded to gastric distension after bilateral vagotomy. Results of these data supported the concept that a group of C(1)-C(2) spinal neurons might play a role in processing sensory information from the stomach that travels in vagal and spinal visceral afferent fibers.     

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20–100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg IV) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p<0.05) and 1 mg/kg (p<0.05), respectively. Naloxone (0.4 mg/kg IV) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.     

Characterization of superficial T13-L2 dorsal horn neurons encoding for colorectal distension in the rat: comparison with neurons in deep laminae

Fifty-five neurons responsive to colorectal distension located in the superficial spinal dorsal horn (0.0-0.3 mm ventral to the cord dorsum) of the T13-L2 spinal segments of pentobarbital-anesthetized, physiologically intact or spinalized (C1 transection), decerebrate rats were characterized. These neurons could be separated into three groups based upon their response to an 80 mm Hg, 20 s colorectal distension: (1) short latency-abrupt (SL-A) neurons (n = 22) that were excited by colorectal distension at a short latency (less than 1 s) and abruptly terminated responses following the termination of the distending stimulus; (2) short latency-sustained (SL-S) neurons (n = 26) that were excited by colorectal distension at a short latency (less than 1 s) and demonstrated sustained responses (greater than 4 s) following termination of the distending stimulus; and (3) INHIB neurons (n = 7) that were spontaneously active and were inhibited by colorectal distension. All 55 neurons had convergent cutaneous receptive fields (i.e. were 'viscerosomatic'), exhibiting excitatory responses to noxious (pinch/heat) and/or non-noxious (brush) stimuli. Neurons excited by colorectal distension also demonstrated monotonic, accelerating responses to graded colorectal distension, were excited by the intraarterial administration of bradykinin, could be antidromically activated by electrical stimulation in the caudal ventrolateral medulla and were subject to tonic descending inhibitory modulation as evidenced by more vigorous responses to distension when rats were reversibly spinalized using a cold block.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of neurons in the lateral thalamus of the cat to stimulation of urinary bladder, colon, esophagus, and skin

In seven female α-chloralose-anesthetized cats, 52 lateral thalamic neurons were tested with noxious distension of the urinary bladder, the distal colon and the lower esophagus. In addition, the neurons were characterized with innocuous and noxious mechanical stimulation of the skin and deep structures. Of the 52 neurons tested, 32 (62%) were visceroceptive. Of these visceroceptive neurons, 20 (63%) were located in the periphery of the ventral posterolateral nucleus (VPL_p), 10 (31%) in the adjacent posterior complex (PO), and two (6%) in the ventrolateral nucleus (VL). No differences were found with respect to location between neurons responsive or unresponsive to visceral stimulation. Ten neurons (31%) received input from more than one viscus and, therefore, showed viscerovisceral convergence. Excitatory or “inhibitory” responses were elicited by stimulation of the esophagus in 21 neurons, of the colon in 13, and of the urinary bladder in 11 neurons. No indications were found for a segregation of neurons responsive to a certain viscus and their location in VPL_p or PO. Of 51 neurons, for which a somatic receptive field was determined, 44 (86%) exhibited low threshold type (LT), and seven (14%) wide dynamic range type (WDR) responses. The data indicate that there might exist a somatovisceral coregistration, because many neurons (69%) had homosegmental receptive fields, and bladder stimulation was the most successful stimulus. It is concluded that VPL_p and the adjacent PO in the cat play a role in the perception and localization of painful events originating from thoracic and pelvic organs.     

Responses of rat spinal neurones to natural and electrical stimulation of colonic afferents: effect of inflammation

Single unit electrical activity has been recorded from 107 neurones excited by electrical stimulation of the pelvic nerve in or around lamina X of the L6-S1 spinal cord in anaesthetised rats. Responses to colorectal distension (CRD; 30 s, 5-80 mmHg) and to somatic electrical and mechanical stimulation were characterised. Of 107 neurones excited by pelvic nerve stimulation, 58 (54%) were affected by CRD: 46 neurones were excited (39 with a sustained response and 7 with an on-off response) and 12 neurones were inhibited. The vast majority of the neurones affected by CRD (54/58) had nociceptive somatic receptive fields. Neurones excited by CRD showed graded stimulus response functions in the noxious range (20-80 mmHg), except for two neurones which only encoded stimulus intensity below 20 mmHg. Neurones inhibited by CRD had significantly larger somatic receptive fields, and more superficial recording sites than those excited by CRD. A group of 12 neurones with sustained excitatory responses to CRD were characterised before and 45 min after intracolonic instillation of 1 ml 0.6% acetic acid. Colon inflammation provoked a significant increase in responses to CRD and to pelvic nerve stimulation (n=12), but no significant change in responses to pinch of their somatic receptive field (n=10). We conclude that of these neurones, the population with excitatory sustained responses to CRD are those likely responsible for processing information leading to acute pain sensations from the colon, and also show central sensitisation after colon inflammation, suggesting they play an important role in development of colonic hyperalgesia.     

Intradermal capsaicin inhibits lumbar dorsal horn neuronal responses to colorectal distention

The purpose of this study was to examine the effect of cutaneous inflammation on the responses of viscerosomatic convergent dorsal horn neurons to graded colorectal distension (CRD) and cutaneous mechanical stimulation. Responses of single viscerosomatic neurons in the lumbar dorsal horn of the rat spinal cord to CRD and to cutaneous stimuli were recorded before and 50 min after cutaneous inflammation induced by intradermal injection of capsaicin in the receptive field (RF) or in the ipsilateral and contralateral forepaw. Capsaicin injection in the RF induced an increase in the spontaneous activity of dorsal horn neurons, an expansion in the size of their RF and facilitated their responses to cutaneous stimuli. An injection placed in the center of the RF attenuated the responses to noxious CRD. Capsaicin injection in the forepaw caused a significant decrease in the responses to CRD but not to cutaneous stimuli. These results indicate that the inhibitory effects, evoked by cutaneous inflammation, can modulate the responses of dorsal horn neurons to CRD, independent of its effect on the responses to cutaneous mechanical stimuli.     

Parametric Assessment of Spinal Cord Stimulation on Bladder Pain—Like Responses in Rats

ObjectivesSpinal cord stimulation (SCS) for the treatment of pelvic visceral pains has been understudied and underused. The goal of the current study was to examine multiple stimulation parameters of SCS to determine optimal settings for the inhibition of responses to urinary bladder distension (UBD) in animal models of bladder pain as a guide for human studies.Materials and MethodsAdult, female isoflurane/urethane-anesthetized rats underwent a T13/L1 mini-laminectomy sufficient to implant an SCS paddle lead for neuromodulation. Silver wire electrodes were inserted into the external oblique musculature. A 22-gauge angiocatheter was placed transurethrally into the bladder and used to deliver phasic, air UBDs at pressures of 10 to 60 mm Hg and visceromotor (abdominal contractile) electromyographic responses to UBD measured in the presence and absence of SCS. Electromyographic activity was quantified using standard differential amplification and rectification. Parameter settings for SCS included both conventional (10, 50, 100 Hz) and high frequency (1,000, 5,000, and 10,000 Hz) biphasic square wave pulses with 50 to 200 μs durations. To create states of hypersensitivity, pretreatment of adult rats included an intravesical zymosan infusion 24 hours before testing with and without a preceding episode of neonatal bladder inflammation.ResultsLow frequency (10, 50, and 100 Hz) 200 μs biphasic pulses at submotor thresholds demonstrated inhibition of visceromotor responses (VMRs) to UBD in rats made hypersensitive to UBD by a protocol that included neonatal cystitis. Onset of inhibitory effects occurred within 20 minutes of beginning SCS. Otherwise, SCS at all other parameters studied and in other tested rat models produced either no significant effect or augmentation of VMRs.ConclusionsDemonstration of inhibitory effects of SCS in a clinically relevant model of bladder pain suggests the potential utility of this therapy in patients with painful bladder disorders.