Acrylamide-induced visceral neuropathy: evidence for the involvement of capsaicin-sensitive nerves of the rat urinary bladder.

The mechanisms underlying the severe urinary retention induced by acrylamide intoxication were studied in detail in the rat. Subcutaneous treatment with acrylamide monomer (50 mg/kg daily for 10 days) almost completely impaired the micturition reflex, resulting in urinary retention. In fact, the ability to eliminate an oral water load was virtually abolished, while bladder filling with saline (transvesical cystometrogram) failed to activate reflex micturition. Instead, a picture of overflow incontinence resulted in urethane-anaesthetized rats, which was not reversed by intravenous administration of 4-aminopyridine. The nerve-mediated contractile response to field stimulation (0.1-20 Hz, 0.5 ms, 60 V) of the isolated bladder was unaffected, thus suggesting the integrity of bladder efferent innervation, and no evidence was found from in vitro experiments that the myogenic contractility of the bladder was depressed by acrylamide treatment. Conversely, the sensory nerve-mediated response to capsaicin was abolished and sensory nerve fibres of the bladder were selectively depleted of their content of substance P- and calcitonin gene-related peptide immunoreactivity following acrylamide treatment. In fact, concentrations of the same neuropeptides in other organs, including the adjoining ureters, were unaffected. As to the urethral segment, including the striated sphincter, the D-tubocurarine (0.2 mM)-sensitive urethral response to electrical stimulation (0.1 Hz, 0.1 ms, 20 V) was significantly reduced in acrylamide-treated animals. At the same level, neurofilament protein immunostaining revealed striking accumulations of neurofilament protein-like material in motor end-plates, thus indicating that neuromuscular junctions of the urethral striated sphincter were severely affected. Thus, the afferent arm of the micturition reflex was shown to be severely deranged by acrylamide intoxication, especially in its capsaicin-sensitive component. Since twitch-like contractions of the urethral striated sphincter are probably involved in promoting bladder voiding, a decreased efficiency of this mechanism could participate in the picture of urinary retention induced by acrylamide.     

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)     

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)     

Proliferation patterns of dorsal root ganglion neurons of cutaneous, muscle and visceral nerves in the rat

In a previous study we provided evidence that dorsal root ganglion (DRG) neurons of different phenotypes have different birthdates. The present study aimed at determining if birthdates of DRG neurons are related to different types of peripheral nerves, namely cutaneous versus muscle, and somatic versus visceral. Pregnant rats were injected intraperitoneally with bromodeoxyuridine (BrdU) to label the neurons on one of the embryonic days E12–E16. When the progeny rats reached adulthood, a mixture of 1% B-fragment of cholera toxin and 1% isolectin B4 from Griffonia simplicifolia I was injected into the peripheral nerves, or a 5% Fluoro-Gold solution was applied to the transected end of the nerves. The saphenous and sural nerves were used as cutaneous nerves, the gastrocnemius nerve as a muscle nerve, the intercostal nerves T9–11 as somatic nerves and the greater splanchnic nerve as a visceral nerve. Cell size measurements were made of DRG neurons labeled from the two cutaneous nerves and the muscle nerve, as well as of neurons of the saphenous and gastrocnemius nerves labeled by BrdU at different embryonic stages. Most of the DRG neurons of the muscle and intercostal nerves were generated early, with peaks at E13, and those of the cutaneous and visceral afferent nerves later, with peaks at E14. The temporal differences were reflected in the cell size spectrum, the muscle nerve having a greater proportion of large neurons compared to the cutaneous nerves. The findings add to previous knowledge regarding the sequence of development of different DRG phenotypes.     

A review of the thoracic splanchnic nerves and celiac ganglia

Anatomical variation of the thoracic splanchnic nerves is as diverse as any structure in the body. Thoracic splanchnic nerves are derived from medial branches of the lower seven thoracic sympathetic ganglia, with the greater splanchnic nerve comprising the more cranial contributions, the lesser the middle branches, and the least splanchnic nerve usually T11 and/or T12. Much of the early anatomical research of the thoracic splanchnic nerves revolved around elucidating the nerve root level contributing to each of these nerves. The celiac plexus is a major interchange for autonomic fibers, receiving many of the thoracic splanchnic nerve fibers as they course toward the organs of the abdomen. The location of the celiac ganglia are usually described in relation to surrounding structures, and also show variation in size and general morphology. Clinically, the thoracic splanchnic nerves and celiac ganglia play a major role in pain management for upper abdominal disorders, particularly chronic pancreatitis and pancreatic cancer. Splanchnicectomy has been a treatment option since Mallet‐Guy became a major proponent of the procedure in the 1940s. Splanchnic nerve dissection and thermocoagulation are two common derivatives of splanchnicectomy that are commonly used today. Celiac plexus block is also a treatment option to compliment splanchnicectomy in pain management. Endoscopic ultrasonography (EUS)‐guided celiac injection and percutaneous methods of celiac plexus block have been heavily studied and are two important methods used today. For both splanchnicectomies and celiac plexus block, the innovation of ultrasonographic imaging technology has improved efficacy and accuracy of these procedures and continues to make pain management for these diseases more successful. Clin. Anat. 23:512–522, 2010. © 2010 Wiley‐Liss, Inc.     

Interactions between tactile and noxious visceral inputs in rat nucleus gracilus

Recent studies have revealed that noxious visceral inputs travel in the dorsal column pathway, and interactions between colorectal noxious and tactile inputs occur in the ventrobasal thalamus. This investigation was to test whether the somatovisceral interactions also take place at a lower level in the dorsal column nuclei. Extracellular single neuron recordings were carried out in nucleus gracilus of anesthetized rats. Forty-three neurons responsive to colorectal distension (CRD) all had excitatory responses to tactile stimuli, and their tactile responses were predominantly (31/43 units) enhanced by preceding CRD. In contrast, the neuronal responses to CRD were reduced in 22/43 units when preceded by tactile stimulation but in two units there was an enhancement. The similarity and differences in the gracile response features in comparison with the thalamic recordings suggest that somatovisceral interactions take place at multiple levels in the dorsal column-medial lemniscus system.     

Perivascular nerves in the rat submandibular salivary gland.

Perivascular nerves in the rat submandibular salivary gland have been studied using a variety of histochemical procedures coupled with electron microscopy. Two principal nerve types, adrenergic and cholinergic, appear to predominate and are localized principally around arterioles. Venules are rarely innervated. The possibility that a non-adrenergic non-cholinergic nerve population might influence blood flow is discussed critically in the light of anatomical and physiological findings.     

胸神经后根的显微外科解剖

目的：为胸部选择性脊神经后根切断术(SPR术)提供可靠的后根分束的解剖学基础。方法：对成人尸体胸神经后根的自然分束和后根问神经纤维联系(CR)进行显微外科解剖学观测。结果：1条胸神经后根有4～6条根丝组成,然后形成2～4根神经亚束,最后形成上、下2股神经束。后根问神经纤维联系出现率为55．4％,根据形状可分为5型,根据位置可分为3类。结论：胸神经后根各级神经分束较易分离,神经纤维联系较为简单,有利于临床医生进行SPR术。     

Anatomy of thoracic splanchnic nerves for surgical resection

Thoracic splanchnic nerves conduct pain sensation from the abdominal organs around the celiac ganglion. Splanchnicectomy is the procedure used mainly for the control of intractable visceral pain. Forty-six human posterior thoracic walls were dissected. The formation pattern, course, and incidence of communication of the thoracic splanchnic nerves were investigated. The greater splanchnic nerves (GSNs) were formed by nerve branches from the T4-T11 thoracic sympathetic ganglia and the most common type was formed by T5-T9 (21.7%). The uppermost branches originated from T4-T9 while the lowermost branches emanated from the T7-T11. Two to seven ganglia contributed to the GSNs. In 54.3% of the specimens, at least one ganglion in the GSN-tributary ganglionic array did not branch to the GSN. The lesser splanchnic nerves (LSNs) were formed by the nerve branches of the T8-T12 thoracic sympathetic ganglia and the most common type was formed by T10 and T11 (32.6%). One to five ganglia were involved in the LSNs. The least splanchnic nerves (lSNs) were composed of branches from the T10-L1 thoracic sympathetic ganglia and the most common type was composed of nerve branches from T11 and T12 or from T12 only (each 30.4%). One to three ganglia were involved in the lSNs. In 54.3% of the specimens, interconnection between the GSNs and the LSNs existed, bringing the possible bypass around the transection of the GSNs. The splanchnic nerves that appear in textbooks occurred in a minority of our specimens. We provided expanded anatomical data for splanchnicectomy in this report.     

The three-dimensional distribution of nerves along the entire intrapulmonary airway tree of the adult rat and the anatomical relationship between nerves and neuroepithelial bodies

Using airway microdissection and three-dimensional confocal microscopy techniques in combination with the immunomarkers protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP), we defined the distribution of small afferent nerves fibers and all nerves throughout the intrapulmonary airways, along with the distribution of airway neuroendocrine cells and neuroepithelial bodies. We found (i) the presence of CGRP-and PGP 9.5-positive structures along the entire intrapulmonary airway tree of adult rats, (ii) decreasing nerve density from more proximal to more distal generations of conducting airways, (iii) the presence of nerve fibers in terminal bronchioles, (iv) the asymmetrical distribution of nerves within a single generation of intrapulmonary airway with regard to associated vessels, (v) the frequent interchange of single nerve fibers across epithelial and sub-epithelial compartments without termination, and (vi) a definably intimate relationship between afferent nerves and neuroepithelial bodies (NEBs) (i.e., 58% of NEBs studied were observed to have nerve fibers coursing through them, indicating direct connections). We conclude that the distribution of nervous elements (nerve fibers and neuroendocrine cells) within the intrapulmonary airways is highly heterogeneous, varying between airway levels and locally within a specific airway level.     

大鼠舌组织中肥大细胞与肽能神经纤维的分布

目的探讨舌组织内肥大细胞与肽能神经的关系及其功能意义。方法采用甲苯胺蓝染色和免疫组织化学ABC染色法对10只Wistar大鼠舌组织进行SP、VIP和NPY染色。结果经与甲苯胺蓝邻片对比观察,舌组织内肥大细胞分别呈SP、VIP和NPY免疫反应性;在舌组织固有层及肌间结缔组织中还分布有丰富的SP、VIP和NPY免疫反应阳性纤维;在肽能神经纤维附近或周围可见有免疫反应阳性的肥大细胞,这些肥大细胞与神经纤维紧密相靠或接触。结论 大鼠舌组织内肥大细胞和神经纤维分别呈SP、VIP和NPY免疫反应性,提示肥大细胞与周围神经无论是在形态还是在功能上有着密切的联系。     

Evidence for a visceral afferent origin of substance P-like immunoreactivity in lamina V of the rat thoracic spinal cord

A visceral afferent origin of substance P-like immunoreactivity in lamina V of the lower thoracic spinal cord of the rat was investigated. In transverse sections from normal animals there was a moderately dense substance P-immunoreactive innervation of lamina V. In some sections there was a dorsoventrally orientated fibre bundle from the superficial dorsal horn entering lamina V. In parasagittal sections, substance P-immunoreactivity in lamina V was found arranged in clusters, with a periodicity in the rostrocaudal axis of 200-600 microns. In some cases these were seen to be continuous with a dorsoventrally orientated fibre bundle from the superficial dorsal horn. After section of the splanchnic nerve there was a consistent reduction in the density of the substance P-like immunoreactivity in lamina V, with fewer clusters on the operated side. Adult rats treated neonatally with capsaicin showed a substantial reduction of substance P-immunoreactivity in laminae I and II and the virtual abolition of staining in lamina V. These results provide evidence of a visceral origin for some of the substance P-like immunoreactivity in lamina V of the rat thoracic spinal cord. In addition, they confirm that most of the substance P-immunoreactivity in the dorsal horn is of primary afferent origin.     

The visceral sector of the thalamic reticular nucleus in the rat.

Visceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, effecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector of the thalamic reticular nucleus. No connections from the thalamic reticular nucleus have been described to the visceral sensory thalamus. We used axonal tracing techniques to study the possible existence of reciprocal connections between the visceral sensory relay in the lateral ventroposterior parvicellular thalamic nucleus, and the reticular nucleus of the thalamus. We also studied the projections from the visceral sensory cortex, located in the granular insular cortex in the rat, to the reticular nucleus of the thalamus. We found a convergent input from both thalamic and cortical sensory visceral regions to the same sector of the reticular nucleus of the thalamus. This visceral sector in turn sent GABAergic feedback connections to the lateral ventroposterior parvicellular thalamic nucleus. In addition, the visceral thalamus received histaminergic projections from the tuberomammillary nucleus, and noradrenergic projections from the locus coeruleus; both nuclei belong to the ascending activating system.Our findings indicate that the visceral sensory thalamocortical pathway is connected to the same subcortical structures that provide attention mechanisms for other thalamocortical systems.