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Irving Nadelhaft

Bio: Irving Nadelhaft is an academic researcher from United States Department of Veterans Affairs. The author has contributed to research in topics: Spinal cord & Urethral sphincter. The author has an hindex of 17, co-authored 19 publications receiving 2260 citations. Previous affiliations of Irving Nadelhaft include Veterans Health Administration & University of Pittsburgh.

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TL;DR: The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays.
Abstract: Electrophysiological and horseradish peroxidase (HRP) techniques have provided new insights into the organization of the sacral parasympathetic reflex pathways to the large intestine and urinary bladder. The innervation of the two organs arises from separate groups of sacral preganglionic cells: (1) a dorsal band of cells in laminae V and VI providing an input to the intestine; and (2) a lateral band of cells in lamina VII providing an input to the bladder. These two groups of cells were separated by an interband region containing tract cells and interneurons. Neurons in the interband region received a visceral afferent input and exhibited firing correlated with the activity of intestine and urinary bladder. It seems reasonable therefore to consider the interband region as a third component of the sacral parasympathetic nucleus. Anterograde transport of HRP revealed that visceral afferents from the intestine and bladder projected into the parasympathetic nucleus. Most of the projections were collaterals from afferent axons in Lissauer's tract that passed in lamina I laterally and medially around the dorsal horn. These afferent collaterals were located in close proximity to preganglionic perikarya and dendrites in laminae I, V and VI. The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays (45-70 msec). The reflex pathways mediating defecation and micturition in cats with an intact neuraxis were markedly different. Defecation was dependent upon a spinal reflex with unmyelinated (C-fiber) peripheral afferent and efferent limbs. On the other hand, micturition was mediated by a spinobulbospinal pathway with myelinated peripheral afferent (A-fiber) and efferent axons (B-fiber). Transection of the spinal cord at T12-L2 blocked the micturition reflex but only transiently depressed the defecation reflex. In chronic spinal cats the micturition reflex recovered 1-2 weeks after spinalization; however, in these animals bladder-to-bladder micturition reflexes were elicited by C-fiber rather than A-fiber afferents. The C-fiber afferent-evoked reflex was weak or undetectable in animals with an intact neuraxis. Transection of the spinal cord also changed the micturition reflex in neonatal kittens (age 5-28 days). In neonates with an intact neuraxis bladder-to-bladder reflexes occurred via a long latency spinobulbospinal pathway (325-430 msec). The long latency is attributable to the slow conduction velocity in immature unmyelinated peripheral and central axons. In chronic spinal kittens (3-7 days after spinalization) the long latency reflex was abolished and a shorter latency (90-150 msec) bladder reflex was unmasked. The emergence of this spinal pathway may reflect axonal sprouting and the formation of new reflex connections within the sacral parasympathetic nucleus.

461 citations

Journal ArticleDOI
TL;DR: The widespread rostrocaudal extent of the pelvic primary afferent projection is consistent with the necessity for the integration of somatic and autonomatic elements from various levels of the lumbo‐sacral‐coccygeal spinal cord in the performance of pelvic visceral functions.
Abstract: The central distribution of visceral primary afferent fibers from the pelvic nerve of the cast and the relationship of these fibers to preganglionic neurons of the sacral parasympathetic neurons (SPN) have been studied. Horseradish peroxidase (HRP) applied to the cut pelvic nerve was detected ipsilaterally in preganglionic neurons and dorsal root ganglion cells (segments S1-S3), and in central afferent projections to Lissauer's tract (LT), the dorsal columns, the dorsolateral funiculus, and spinal gray matter. The afferent projections were strongest in the region of the SPN (S1-S3) but extended far beyond its limits (e.g., LT was labeled from L4 to Cx7). In the transverse plane, collateral fiber bundles formed a thin shell around the dorsal horn predominantly within lamina I and expanded into terminal fields in the gray matter. The more prominent lateral collateral projection (LCP) extended into laminae V and VI, whereas the medial one (MCP) ended in the dorsal commissure. In longitudinal planes these projections exhibited a periodicity with an interval of approximately 200 micrometer. The distribution of afferent collateral projections overlaps the regions where many preganglionic neurons and their dendritic extensions are located, and also areas known to contain interneurons involved in visceral pathways. A differential distribution of afferents within the SPN was noted where a higher intensity was observed in proximity to those neurons located in laminae V and VI, which innervate the colon, and a lower intensity near neurons located in Lamina VII which innervate the bladder. This is consistent with the known spinal control of colon reflexes and the supraspinal control of bladder reflexes. The widespread rostrocaudal extent of the pelvic primary afferent projection is consistent with the necessity for the integration of somatic and autonomic elements from various levels of the lumbo-sacral-coccygeal spinal cord in the performance of pelvic visceral functions.

449 citations

Journal ArticleDOI
TL;DR: Sensory neurons of the sacral parasympathetic nucleus were located almost exclusively (98%) within the L6‐S1 spinal cord segments and fiber bundles formed fiber bundles that were spaced by approximately 100 μm between centers when observed in the horizontal plane.
Abstract: Preganglionic neurons of the sacral parasympathetic nucleus (SPN) were located almost exclusively (98%) within the L6-S1 spinal cord segments. The SPN contained approximately 550 neurons of medium size (10 X 20 micron). These were mainly located in the intermediolateral gray matter and had dendrites that extended into the dorsolateral funiculus, along the lateral marginal zone of the dorsal horn, and medially into the dorsal gray commissure. Labeled dorsal root ganglion cells were almost all located (95%) in the L6 and S1 ganglia. An average of approximately 1,500 sensory neurons were found. These were small cells (17 X 25 micron) whose central processes entered Lissauer's tract from which two groups of collaterals emerged: 1) a prominent lateral pathway along the lateral margin of the dorsal horn that extended into the region of the SPN and also into the dorsal gray commissure, 2) a less prominent medial pathway extending around the dorsal margin of the dorsal horn to terminate in the dorsal gray commissure. These two collateral groups formed fiber bundles that were spaced by approximately 100 micron between centers when observed in the horizontal plane. A third afferent bundle, composed of rostrocaudally oriented fibers, was located in the sagittal plane immediately ventral to the central canal. Comparisons are made between the results in rats and the results of similar experiments performed in cats and monkeys.

427 citations

Journal ArticleDOI
TL;DR: Application of horseradish peroxidase to the central cut end of the pudendal nerve labeled motoneurons in the ipsilateral spinal cord primarily in the S1 and L7 segments.
Abstract: The horseradish peroxidase tracing technique was utilized to study the distribution of motoneurons and primary afferent neurons contributing fibers to the pudendal nerve in the monkey. Application of horseradish peroxidase to the central cut end of the pudendal nerve labeled motoneurons in the ipsilateral spinal cord primarily in the S1 and L7 segments. In transverse sections these neurons were distributed within an oval area (Onuf's nucleus) with an average dimension of 360 × 290 μm, located at the base of the ventral horn, medial to the lateral motor nuclei. An average of 418 (range: 170–577) medium-sized (44 × 26 μm) neurons were labeled per animal. In longitudinal sections the nucleus appeared as a beaded column of cells extending 9.3 mm rostrocaudally with a prominent network of longitudinal dendrites. In the transverse plane, other groups of dendrites were observed: one group extended dorsomedially toward the central canal, while a second group extended dorsolaterally to the intermediolateral gray, with some of the latter dendritic processes following the lateral border of the ventral horn. An average of 9,200 afferent neurons were labeled in the dorsal root ganglia of each animal. Approximately 85% of these cells were located in a single dorsal root ganglion (S1 or S2). This ganglion was always located one spinal segment caudal to the segment containing the majority of cells in Onuf's nucleus. In the spinal cord, afferent labeling in the dorsal columns and Lissauer's tract extended from S3 to at least L1. The density of afferent labeling in the spinal cord paralleled the number of labeled dorsal root ganglion cells in the corresponding segments. From Lissauer's tract and the dorsal columns a prominent collateral fiber bundle passed medially over the apex of the dorsal horn to the dorsal commissure and to medial laminae I–IV of the dorsal horn. A much less prominent pathway passed ventrally along the lateral edge of the dorsal horn to lamina V, where a few collaterals continued medially to the dorsal commissure. The majority of labeled lateral afferent axons ended slightly dorsal to the sacral parasympathetic nucleus. A comparison of the present findings with previous descriptions of the sacral visceral pathways shows a considerable overlap in certain areas of the spinal cord of pudendal and pelvic nerve afferent and efferent systems. This close anatomic relationship is consistent with the physiological observation that somatovisceral integration in the lumbosacral spinal cord is essential for the normal regulation of micturition, defecation, and sexual function.

147 citations

Journal ArticleDOI
TL;DR: The central projection of hypogastric nerve primary afferents was qualitatively similar to the distribution of visceral afferent projections at other levels of the spinal cord.
Abstract: The spinal distribution of sympathetic preganglionic neurons (PGN) and visceral primary afferent neurons sending axons into the hypogastric nerve of the cat has been studied with HRP tracing techniques After application of HRP to the cat hypogastric nerve, labeled PGN were identified in segments L2-L5 Most of these neurons were oriented transversely and were divided approximately equally between two nuclei: the principal nucleus and the intercalated nucleus Cells were distributed in clusters at 160-361-microns intervals along the length of the cord Sensory neurons were labeled in dorsal root ganglia from T12 to L5 Central axons of these visceral afferents were observed in the medial half of Lissauer's tract from T13 to L7 Afferent axon collaterals extended through lamina I on both sides of the dorsal horn but were most prominent on the lateral side, where they continued into lateral lamina V and VII, often overlapping the dorsal dendrites of PGN in this region Labeled afferent projections exhibited a periodic distribution in lamina I with clusters of axons occurring at 235-343-microns intervals in the rostrocaudal axis The central projection of hypogastric nerve primary afferents was qualitatively similar to the distribution of visceral afferent projections at other levels of the spinal cord

145 citations


Cited by
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Journal ArticleDOI
01 Sep 1998-Neuron
TL;DR: It is shown that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH < or = 5.9) activate VR1 at room temperature, and VR1 can be viewed as a molecular integrator of chemical and physical stimuli that elicit pain.

2,959 citations

Journal ArticleDOI
TL;DR: The neural control of micturition is reviewed and how disruption of this control leads to abnormal storage and release of urine.
Abstract: Micturition, or urination, occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. The neural circuitry that controls this process is complex and highly distributed: it involves pathways at many levels of the brain, the spinal cord and the peripheral nervous system and is mediated by multiple neurotransmitters. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary or reflex micturition, leading to urinary incontinence. This is a major health problem, especially in those with neurological impairment. Here we review the neural control of micturition and how disruption of this control leads to abnormal storage and release of urine.

1,138 citations

Journal ArticleDOI
TL;DR: This Review provides a broad overview of the field of neurogastroenterology, with a focus on the roles of the ENS in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement.
Abstract: Neurogastroenterology is defined as neurology of the gastrointestinal tract, liver, gallbladder and pancreas and encompasses control of digestion through the enteric nervous system (ENS), the central nervous system (CNS) and integrative centers in sympathetic ganglia. This Review provides a broad overview of the field of neurogastroenterology, with a focus on the roles of the ENS in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement. Digestion is controlled through the integration of multiple signals from the ENS and CNS; neural signals also pass between distinct gut regions to coordinate digestive activity. Moreover, neural and endocrine control of digestion is closely coordinated. Interestingly, the extent to which the ENS or CNS controls digestion differs considerably along the digestive tract. The importance of the ENS is emphasized by the life-threatening effects of certain ENS neuropathies, including Hirschsprung disease and Chagas disease. Other ENS disorders, such as esophageal achalasia and gastroparesis, cause varying degrees of dysfunction. The neurons in enteric reflex pathways use a wide range of chemical messengers that signal through an even wider range of receptors. These receptors provide many actual and potential targets for modifying digestive function.

1,080 citations

Journal ArticleDOI
TL;DR: The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light.
Abstract: The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light. In particular, two major issues have seen considerable progress in the past decade. First, the pathways that provide visceral sensation to conscious perception at a cortical level have been elucidated in both animals and humans. The nociceptive system runs in parallel to the pathways carrying visceral sensation from the cranial nerves and may be considered in itself a component of visceral sensation. Second, structures in the central nervous system that generate patterns of autonomic response have been identified. These pattern generators are located at multiple levels of the central nervous system, and they can be combined in temporal and spatial patterns to subserve a wide range of behavioral needs.

662 citations