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Frank L. Rice - One of the best experts on this subject based on the ideXlab platform.
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excessive peptidergic sensory Innervation of cutaneous arteriole venule shunts avs in the palmar glabrous skin of fibromyalgia patients implications for widespread deep tissue pain and fatigue
Pain Medicine, 2013Co-Authors: Frank L. Rice, Phillip J Albrecht, Charles Argoff, James R Storey, James WymerAbstract:OBJECTIVE: To determine if peripheral neuropathology exists among the Innervation of cutaneous arterioles and arteriole-venule shunts (AVS) in fibromyalgia (FM) patients. SETTING: Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic Innervation, and vasodilatory small-fiber sensory Innervation. Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action. SUBJECTS: Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies. AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects. METHODS: Multimolecular immunocytochemistry to assess different types of cutaneous Innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions. RESULTS: AVS had significantly increased Innervation among FM patients. The excessive Innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers. In contrast, sensory and sympathetic Innervation to arterioles remained normal. Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic Innervation exerts an inhibitory modulation of sensory activity. CONCLUSIONS: The excessive sensory Innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients. Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand. Therefore, blood flow dysregulation as a result of excessive Innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM. SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory Innervation.
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Innervation of the digit on the forepaw of the raccoon.
The Journal of Comparative Neurology, 2000Co-Authors: Frank L. Rice, Douglas D. RasmussonAbstract:The Innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber Innervation terminates in the epidermis and on the microvasculature. The Innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel Innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffinilike endings at the transition from the distal phalanx and unmyelinated Innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber Innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular Innervation is peptidergic, whereas most of the unmyelinated epidermal Innervation is nonpeptidergic. J. Comp. Neurol. 417: 467‐ 490, 2000. © 2000 Wiley-Liss, Inc. Indexing terms: digit; cutaneous Innervation; vascular Innervation; sensory endings
Robin F. Krimm - One of the best experts on this subject based on the ideXlab platform.
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Taste Bud-Derived BDNF Is Required to Maintain Normal Amounts of Innervation to Adult Taste Buds
eNeuro, 2015Co-Authors: Lingbin Meng, Lisa Ohman-gault, Robin F. KrimmAbstract:Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory Innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud Innervation during development, it might function to maintain Innervation during adulthood. If so, taste buds should lose Innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately one-half of the Innervation to taste buds was lost, and taste buds became smaller because of the loss of taste bud cells. Individual taste buds varied in the amount of Innervation each lost, and those that lost the most Innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating Innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of Innervation in adulthood.
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postnatal reduction of bdnf regulates the developmental remodeling of taste bud Innervation
Developmental Biology, 2015Co-Authors: Tao Huang, Robin F. KrimmAbstract:The refinement of Innervation is a common developmental mechanism that serves to increase the specificity of connections following initial Innervation. In the peripheral gustatory system, the extent to which Innervation is refined and how refinement might be regulated is unclear. The initial Innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial Innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud Innervation during postnatal development. An analysis of BDNF expression in Bdnf(lacZ/+) mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory Innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of Innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing Innervation. This reduction of Innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory Innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development.
Arieh L Shalhav - One of the best experts on this subject based on the ideXlab platform.
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contribution of renal Innervation to hypertension in rat autosomal dominant polycystic kidney disease
Experimental Biology and Medicine, 2008Co-Authors: Vincent H Gattone, Tiberio M Siqueira, Charles R Powell, Chad M Trambaugh, James E Lingeman, Arieh L ShalhavAbstract:The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal Innervation has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal Innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal Innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Operated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal Innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects of renal denervation on the renin angiotensin system.
Sture Forsgren - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical analysis of wrist ligament Innervation in relation to their structural composition
Journal of Hand Surgery (European Volume), 2007Co-Authors: Elisabet Hagert, Marc Garciaelias, Sture Forsgren, Bjornove LjungAbstract:PURPOSE: To analyze ligament Innervation and the structural composition of wrist ligaments to investigate the potential differences in sensory and biomechanical functions. METHODS: The ligaments analyzed were the dorsal radiocarpal, dorsal intercarpal, scaphotriquetral, dorsal scapholunate interosseous, scaphotrapeziotrapezoid, radioscaphoid, scaphocapitate, radioscaphocapitate, long radiolunate, short radiolunate, ulnolunate, palmar lunotriquetral interosseous, triquetrocapitate, and triquetrohamate ligaments. The ligaments were harvested from 5 cadaveric, fresh-frozen specimens. By using the immunohistochemical markers p75, Protein Gene Product 9.5, and S-100 protein, the mechanoreceptors and nerve fibers could be identified. RESULTS: The Innervation pattern in the ligaments was found to vary distinctly, with a pronounced Innervation in the dorsal wrist ligaments (dorsal radiocarpal, dorsal intercarpal, scaphotriquetral, dorsal scapholunate interosseous), an intermediate Innervation in the volar triquetral ligaments (palmar lunotriquetral interosseous, triquetrocapitate, triquetrohamate), and only limited/occasional Innervation in the remaining volar wrist ligaments. The Innervation pattern also was reflected in the structural differences between the ligaments. When present, mechanoreceptors and nerve fibers were consistently found in the loose connective tissue in the outer region (epifascicular region) of the ligament. Hence, ligaments with abundant Innervation had a large epifascicular region, as compared with the ligaments with limited Innervation, which consisted mostly of densely packed collagen fibers. CONCLUSIONS: The results of our study suggest that wrist ligaments vary with regard to sensory and biomechanical functions. Rather, based on the differences found in structural composition and Innervation, wrist ligaments are regarded as either mechanically important ligaments or sensory important ligaments. The mechanically important ligaments are ligaments with densely packed collagen bundles and limited Innervation. They are located primarily in the radial, force-bearing column of the wrist. The sensory important ligaments, by contrast, are richly innervated although less dense in connective tissue composition and are related to the triquetrum. The triquetrum and its ligamentous attachments are regarded as key elements in the generation of the proprioceptive information necessary for adequate neuromuscular wrist stabilization.
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Distribution of general (PGP 9.5) and sensory (substance P/CGRP) Innervations in the human patellar tendon
Knee Surgery Sports Traumatology Arthroscopy, 2006Co-Authors: Patrik Danielson, Håkan Alfredson, Sture ForsgrenAbstract:There is no information on the pattern of blood vessel Innervation, and in principle no information on Innervation in general, in the human patellar tendon. In the present study, biopsies from the proximal part of normal and pain-free patellar tendons (11 men, mean age 33 years) were examined. The specimens were evaluated by using antibodies against the general nerve marker protein gene-product 9.5 (PGP 9.5) and the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and immunohistochemistry. It was observed that the arteries, and to some extent the small vessels, in the loose paratendinous connective tissue were supplied with PGP 9.5- as well as SP- and CGRP-Innervations. There was a marked PGP 9.5-like immunoreaction (LI), and to some extent also SP- and CGRP-LI, in the large nerve fascicles in this tissue. In the tendon tissue proper, PGP 9.5-LI was detected in nerve fibers located in the vicinity of some of the blood vessels and in thin nerve fascicles. There was a low degree of SP- and CGRP-Innervation in the tendon tissue proper. The observations give a morphologic correlate for the occurrence of nerve-mediated effects in the patellar tendon. Particularly it seems as if there is a marked nerve-mediated regulation of the blood vessels supplying the tendon, at the level where they course in the loose paratendinous connective tissue.
Phillip J Albrecht - One of the best experts on this subject based on the ideXlab platform.
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excessive peptidergic sensory Innervation of cutaneous arteriole venule shunts avs in the palmar glabrous skin of fibromyalgia patients implications for widespread deep tissue pain and fatigue
Pain Medicine, 2013Co-Authors: Frank L. Rice, Phillip J Albrecht, Charles Argoff, James R Storey, James WymerAbstract:OBJECTIVE: To determine if peripheral neuropathology exists among the Innervation of cutaneous arterioles and arteriole-venule shunts (AVS) in fibromyalgia (FM) patients. SETTING: Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic Innervation, and vasodilatory small-fiber sensory Innervation. Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action. SUBJECTS: Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies. AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects. METHODS: Multimolecular immunocytochemistry to assess different types of cutaneous Innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions. RESULTS: AVS had significantly increased Innervation among FM patients. The excessive Innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers. In contrast, sensory and sympathetic Innervation to arterioles remained normal. Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic Innervation exerts an inhibitory modulation of sensory activity. CONCLUSIONS: The excessive sensory Innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients. Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand. Therefore, blood flow dysregulation as a result of excessive Innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM. SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory Innervation.
