Presence and distribution of sensory nerve fibers in human peritoneal adhesions

Abstract

Objective: To 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 data: Peritoneal 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.

Methods: Human 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.

Results: Nerve 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.

Conclusions: This 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.

Figure 1. A nerve (arrows) in a human peritoneal adhesion. Adhesions were highly vascularized and contained dense collagen bundles (Masson’s trichrome, ×430).

Figure 2. Calcitonin gene-related peptide-immunoreactive nerve fibers in human adhesions. The nerve fiber (green) shows typical varicosities in parallel or a beaded appearance. Blood vessels were immunoreactive for von Willebrand factor (red) (×1,500).

Figure 3. Colocalization of nerve fibers with blood vessels. Substance P-immunoreactive nerve fibers (green) were found associated with blood vessels immunoreactive for von Willebrand factor (red) in peritoneal adhesions. In addition, some fibers were independent of vessels (×1,500).

Figure 4. Extensive nerve meshwork within a blood vessel wall in human peritoneal adhesions (arrows). Note the circumferential and horizontal network of nerve fibers immunoreactive to Calcitonin gene-related peptide within the media (thick arrow) and adventitial layer (thin arrows) (×280).

Figure 5. Distribution of blood vessels and nerve fibers in human peritoneal adhesions demonstrated in whole-mount preparations by acetylcholinesterase histochemistry. Generally, nerve fibers (black) accompanied blood vessels (white) arranged parallel to the long axis of the adhesion, but some nerve fibers branched independently (arrows) (×18).

Figure 6. Transmission electron microscopy of a human adhesion showing myelinated (thick arrows) and nonmyelinated nerve fibers (thin arrows) embedded within the extracellular matrix. Schwann’s cells (S) were found surrounding the axons with associated collagen fibers (×4,800).