ObjectiveTo assess the distribution and type of nerve fibers present in human peritoneal adhesions and to relate data on location and size of nerves with estimated age and with clinical parameters such as reports of chronic pelvic pain. Summary Background DataPeritoneal adhesions are implicated in the cause of chronic abdominopelvic pain, and many patients are relieved of their symptoms after adhesiolysis. Adhesions are thought to cause pain indirectly by restricting organ motion, thus stretching and pulling smooth muscle of adjacent viscera or the abdominal wall. However, in mapping studies using microlaparoscopic techniques, 80% of patients with pelvic adhesions reported tenderness when these structures were probed, an observation suggesting that adhesions themselves are capable of generating pain stimuli. MethodsHuman peritoneal adhesions were collected from 25 patients undergoing laparotomy, 20 of whom reported chronic pelvic pain. Tissue samples were prepared for histologic, immunohistochemical, and ultrastructural analysis. Nerve fibers were characterized using antibodies against several neuronal markers, including those expressed by sensory nerve fibers. In addition, the distribution of nerve fibers, their orientation, and their association with blood vessels were investigated by acetylcholinesterase histochemistry and dual immunolocalization. ResultsNerve fibers, identified histologically, ultrastructurally, and immunohistochemically, were present in all the peritoneal adhesions examined. The location of the adhesion, its size, and its estimated age did not influence the type of nerve fibers found. Further, fibers expressing the sensory neuronal markers calcitonin gene-related protein and substance P were present in all adhesions irrespective of reports of chronic abdominopelvic pain. The nerves comprised both myelinated and nonmyelinated axons and were often, but not invariably, associated with blood vessels. ConclusionsThis study provides the first direct evidence for the presence of sensory nerve fibers in human peritoneal adhesions, suggesting that these structures may be capable of conducting pain after appropriate stimulation.Peritoneal adhesions are bands of fibrous tissue that join abdominal organs to each other or the abdominal wall. Adhesions develop rapidly after damage to the peritoneum during surgery, infection, trauma, or irradiation. Postoperative adhesion formation occurs in 93% to 100% of patients undergoing laparotomy, 1 leading to complications such as intestinal obstruction and infertility in women.2-4 Adhesions have also been implicated as a cause of chronic abdominopelvic pain, 5-8 and many patients have been relieved of their symptoms after adhesiolysis.9 -12 Chronic pelvic pain accounts for up to 25% of all gynecologic visits, 30% to 50% of all diagnostic laparoscopic procedures, and approximately 5% of hysterectomies. 13,14 In financial terms, the annual cost of resources for the diagnosis and treatment of women with chronic pelvic pain in the United Kingdom is approximately 拢600...
The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats, capybaras and horses, respectively. The average neuronal size (area of the largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras and horses, respectively. When comparing the three species (average body weight: 200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in line with the variation of body weight. However, the average neuronal size in the capybara deviates from this pattern in being larger than that of in the horse. The rat presented great interindividual variability in all the neuronal parameters. From the data in the literature and our new findings in the capybara and horse, we conclude that some correlations exist between average size of neurons and body size and between total number of neurons and body size. However, these correlations are only approximate and are based on averaged parameters for large populations of neurons: they are less likely to be valid if one considers a single quantitative parameter. Several quantitative features of the nervous tissue have to be taken into account together, rather than individually, when evolutionary trends related to size are considered.
The distribution of afferent axons in the bladder of rats was studied by means of immunohistochemistry for calcitonin gene-related peptide (CGRP), in frozen sections and in wholemount preparations of mucosa and muscle coat. Synaptophysin-immunofluorescence was used for the general detection of all intramural axons. The afferent axons were distributed over four distinct targets: at the base of the epithelium, inside the epithelium, on blood vessels (both arteries and veins) and along muscle bundles. In the mucosa, all the afferent axons, except the perivascular ones, lay either inside the epithelium or in a subepithelial plexus very close to the basal surface of the epithelium. The plexus was thickest in the neck of the bladder and in the initial portion of the urethra, and it became progressively less dense in the adjacent regions; it did not extend beyond the equatorial region, and therefore the mucosa of the cranial region of the bladder had no afferent axons. Most of the axons in the subepithelial plexus were terminal axons and included conspicuous varicosities arranged in very long chains; branching points were numerous, usually at right angles and located at the level of a varicosity; some axons split and then rejoined, forming closed axonal loops. The afferent innervation of the musculature was more diffuse, and appeared uniform throughout the bladder. After unilateral surgical denervation (by excision of the pelvic ganglion 5-7 days earlier) areas of complete denervation were observed, but there were large areas where the innervation was only reduced. The results showed that there is a bilateral innervation of many regions of the mucosa and the musculature, including individual muscle bundles. A substantial number of fibres crossed the midline into the contralateral side of the bladder. CGRP-immunofluorescence in mucosal afferent axons is enhanced in the surviving axons 5 days after contralateral denervation, a change which is interpreted as an early sign of regeneration.
Adhesions in the peritoneal cavity have been implicated in the cause of intestinal obstruction and infertility, but their role in the aetiology of chronic pelvic pain is unclear. Nerves have been demonstrated in human pelvic adhesions, but the presence of pain-conducting fibres has not been established. The purpose of this study was to use an animal model to examine the growth of nerves during adhesion formation at various times following injury and to characterize the types of fibres present. Adhesions were generated in mice by injuring the surface of the caecum and adjacent abdominal wall, with apposition. At 1-8 weeks post-surgery, adhesions were processed and nerve fibres characterized histologically, immunohistochemically, and ultrastructurally. Peritoneal adhesions had consistently formed by 1 week after surgery and from 2 weeks onwards, all adhesions contained some nerve fibres which were synaptophysin, calcitonin gene-related peptide, and substance P-immunoreactive, and were seen to originate from the caecum. By 4 weeks post-surgery, nerve fibres were found to originate from both the caecum and the abdominal wall, and as demonstrated by acetylcholinesterase histochemistry, many traversed the entire adhesion. Ultrastructural analysis showed both myelinated and non-myelinated nerve fibres within the adhesion. This study provides the first direct evidence for the growth of sensory nerve fibres within abdominal visceral adhesions in a murine model and suggests that there may be nerve fibres involved in the conduction of pain stimuli.
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