Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biologic action of extracorporeal shock wave application on the musculoskeletal system is poorly understood. To prove the hypothesis that alterations of tissue concentrations of substance P and prostaglandin E(2) are involved in the biologic action of shock waves, extracorporeal shock waves with energy flux density of 0.9 mJ/mm2 (1500 pulses at 1/second) were applied in vivo to the distal femur of rabbits. The concentrations of substance P and prostaglandin E(2) eluted from the periosteum of the femur were measured. Compared with the untreated contralateral hindlimbs, substance P release from the periosteum from the femur was increased 6 hours and 24 hours after extracorporeal shock wave application, but was decreased 6 weeks after extracorporeal shock wave application. By contrast, extracorporeal shock wave application did not result in altered prostaglandin E(2) release from the periosteum from the femur. Remarkably, there was a close relationship between the time course of substance P release found here, and the well-known clinical time course of initial pain occurrence and subsequent pain relief after extracorporeal shock wave application to tendon diseases. Accordingly, substance P might be involved in the biologic action of extracorporeal shock wave application on tissue of the musculoskeletal system. This is the first study providing insights into the molecular mechanisms of extracorporeal shock wave application to the musculoskeletal system.
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PMID:Substance P and prostaglandin E2 release after shock wave application to the rabbit femur. 1257 24

We have previously demonstrated that Goto-Kakizaki (GK) rats with spontaneous type-2 diabetes and peripheral neuropathy exhibit regional osteopathic changes. In the present study on 18 GK rats and 21 control Wistar rats, the occurrence of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the autonomic neuropeptide Y (NPY) was analysed in bone and joints, dorsal root ganglia and lumbar spinal cord by immunohistochemistry and radioimmunoassay (RIA). Immunohistochemistry disclosed a predominance of immunoreactivities in vessel-related nerve fibers, although some were also seen in free terminals. While SP, CGRP and NPY in periosteum, cortical bone and synovium was confined to neuronal tissue, the bone marrow in addition exhibited an abundance of NPY-positive megakaryocytes. Apart from this cellular source of NPY, the observations suggest that the three neuropeptides analysed in bone and joints are of neuronal origin. Quantification by RIA showed a significant decrease of NPY in cortical bone (-36%), bone marrow (-66%) and ankle (-29%) of GK rats. CGRP was decreased in the spinal cord (-19%) and dorsal root ganglia (-26%) but was unchanged in bone and joints, as with SP. Given the suggested anabolic role of NPY and CGRP on bone, neuropeptidergic deficit in diabetes may prove to be an important factor underlying the development of regional osteopenia.
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PMID:Bone and joint neuropathy in rats with type-2 diabetes. 1509 98

The biologic action of extracorporeal shock wave application on the musculoskeletal system is understood poorly. To prove the hypothesis that alterations of tissue concentrations of substance P and prostaglandin E(2) are involved in the biologic action of shock waves, extracorporeal shock waves with energy flux density of 0.9 mJ/mm(2 )(1500 pulses at 1/s) were applied in vivo to the distal femur of rabbits. The concentrations of substance P and prostaglandin E(2) eluated from the periosteum of the femur were measured. Compared with the untreated contralateral hindlimbs, substance P release from the periosteum from the femur was increased 6 and 24 h after extracorporeal shock wave application, but was decreased 6 weeks after extracorporeal shock wave application. By contrast, extracorporeal shock wave application did not result in altered prostaglandin E(2) release from the periosteum from the femur. Remarkably, there was a close relationship between the time course of substance P release found here, and the well-known clinical time course of initial pain occurrence and subsequent pain relief after extracorporeal shock wave application to tendon diseases. Accordingly, substance P might be involved in the biologic action of extracorporeal shock wave application on tissue of the musculoskeletal system. This is the first study providing insights into the molecular mechanisms of extracorporeal shock wave application to the musculoskeletal system.
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PMID:[Molecular basis for pain mediating properties of extracorporeal shock waves]. 1558 98

Immunohistochemical studies have revealed an extensive network of nerve fibers in the vicinity and within the skeleton, not only in the periosteum of bone but also in cortical and trabecular bone as well as in the bone marrow. Phenotyping of the skeletal nerve fibers have demonstrated the expression of a restrictive panel of different signalling molecules including neuropeptides, neurotransmitters and neurotrophins. In this review, the presence of receptors for the neuropeptides vasoactive intestinal peptide, calcitonin gene-related peptide and substance P on osteoblasts and osteoclasts and the capacity of these receptors to regulate bone formation, osteoclast formation and activity are described. These findings, together with data obtained by chemically and surgically targeted nerve deletion and observations made in paraplegic patients, strongly suggest that neuro-osteogenic interactions play an important role in skeletal function.
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PMID:Neuropeptidergic regulation of bone resorption and bone formation. 1575 12

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16-21 and in neonates and juvenile individuals on postnatal days (PD) 1-28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes.
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PMID:Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43). 1605 Sep

Using immunohistochemical and biochemical techniques, the occurrence of endogenous opioid peptides and their receptors in normal rat bone and joint tissues was investigated. Opioid receptors were detected, quantified, and characterized in homogenates from capsule/synovium and periosteum using radioligand binding assays. Receptor binding of the nonselective opioid [3H]naloxone to tissue homogenates was stereospecific and saturable, showing similar characteristics to that of brain tissue, although with lower binding capacities. By immunohistochemistry, the neuronal occurrence of four different enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta-articular bone, whereas no neuronal dynorphin immunoreactivity was detected. Double-staining studies disclosed that enkephalins coexisted with substance P in primary afferent fibers. The applied techniques can be used to assess changes in the distribution of endogenous opioids and their receptors in joint tissues in conditions associated with pain and inflammation. The endogenous opioid system now demonstrated might be targeted and exploited therapeutically to obtain peripheral control of symptoms in joint disorders.
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PMID:Opioid peptides and receptors in joint tissues: study in the rat. 1664 79

Galanin exerts tonic inhibition of nociceptive input to the central nervous system. Recently, this peptide was demonstrated in several neuronal and non-neuronal structures in bones and joints. In this study, the time of appearance and topographic localization of galanin-containing nerve fibres in bone were studied in rats from gestational day 16 (GD16) to postnatal day 21 (PD21). The tibia was chosen as a model of developing long bone and indirect immunofluorescence combined with confocal laser scanning microscopy was used to identify galanin-immunoreactive (GAL-IR) nerve fibres. The earliest, sparse GAL-IR fibres were observed on GD21 in the perichondrium of both epiphyses and in the periosteum of the diaphysis. From PD1 onwards, GAL-IR fibres were also seen in the bone marrow cavity and in the region of the inter-condylar eminence of the knee joint. Intramedullary GAL-IR fibres in proximal and distal metaphyses appeared around PD1. Some of them accompanied blood vessels, although free fibres were also seen. GAL-IR fibres located in the cartilage canals of both epiphyses were observed from PD7, in the secondary ossification centres from PD10 and in the bone marrow of both epiphyses from PD14. The time course and localization of galanin-containing nerve fibres resemble the development of substance P- and CGRP-expressing nerve fibres, thus suggesting their sensory origin.
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PMID:Development of galanin-containing nerve fibres in rat tibia. 1900 57

Retrograde labeling has been used to identify sensory neurons in the lumbar dorsal root ganglia (DRG) that innervate the rat tibial periosteum, medullary cavity, and trabecular bone. The size, neurochemical profile [isolectin B4 (IB4) binding, substance P (SP), calcitonin gene-related peptide (CGRP), and NF200 immunoreactivity (-IR)], and segmental distribution of sensory neurons innervating each of these bony compartments are reported. After injections of fast blue into the periosteum, medullary cavity, and trabecular bone (epiphysis), retrogradely labeled neurons were observed throughout the ipsilateral (but not contralateral) lumbar DRG. They were predominantly small (<800 microm(2)) or medium-sized (800-1,800 microm(2)) neurons. CGRP-IR and SP-IR were found in 23% and 16% of the retrogradely labeled neurons, respectively. IB4 binding was observed in 20% and NF200-IR in 40% of the retrogradely labeled neurons. There were no significant differences in the percentage of neurons labeled with any one of the antisera following injections into each of the three bony compartments. To allow a direct comparison with sensory neurons innervating cutaneous tissues, injections of fast blue were also made into the skin overlying the tibia. The percentage of CGRP-IR neurons innervating bone was significantly lower than the percentage of CGRP-IR neurons innervating skin (ANOVA; P < 0.05). No other significant differences in the neurochemical profiles of neurons labeled from bone vs. skin were observed. The findings of the present study show that the periosteum, medullary cavity, and trabecular bone are all innervated by sensory neurons that have size and neurochemical profiles consistent with a role in nociception.
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PMID:Size, neurochemistry, and segmental distribution of sensory neurons innervating the rat tibia. 1975 92

Although musculoskeletal pain is one of the most common causes of chronic pain and physical disability in both developing and developed countries, relatively little is known about the nerve fibers and mechanisms that drive skeletal pain. Small diameter sensory nerve fibers, most of which are C-fiber nociceptors, can be separated into two broad populations: the peptide-rich and peptide-poor nerve fibers. Peptide-rich nerve fibers express substance P (SP) and calcitonin gene-related peptide (CGRP). In contrast, the peptide-poor nerve fibers bind to isolectin B4 (IB(4)) and express the purinergic receptor P(2)X(3) and Mas-related G protein-coupled receptor member d (Mrgprd). In the present report, we used mice in which the Mrgprd(+) nerve fibers express genetically encoded axonal tracers to determine the peptide-rich and peptide-poor sensory nerve fibers that innervate the glabrous skin of the hindpaw as compared to the bone marrow, mineralized bone and periosteum of the femur. Whereas the skin is richly innervated by CGRP(+), SP(+), P(2)X(3)(+) and Mrgprd(+) sensory nerve fibers, the bone marrow, mineralized bone and periosteum receive a significant innervation by SP(+) and CGRP(+), but not Mrgprd(+) and P(2)X(3)(+) nerve fibers. This lack of redundancy in the populations of C-fibers that innervate the bone may present a unique therapeutic opportunity for targeting skeletal pain as the peptide-rich and peptide-poor sensory nerve fibers generally express a different repertoire of receptors and channels to detect noxious stimuli. Thus, therapies that target the specific types of C-nerve fibers that innervate the bone may be uniquely effective in attenuating skeletal pain as compared to skin pain.
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PMID:A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain. 1976 46

The anatomical understanding of the pain generators in osteoarthritis (OA) is incomplete and the teaching about these pain generators in medical school anatomy/histology courses is minimal. This review covers the nociceptive innervation of synovial joints for the purposes of teaching. Studies that discuss the presence of neuropeptides involved in pain, such as Substance P (SP) and calcitonin-gene-related peptide, are the focus of this review. Nociceptive free-nerve endings and SP staining nerves are found in the accessory ligaments, synovium, subchondral bone, menisci, and periosteum. The vasculature may also play a role in pain generation through vasospasm or ischemia, but this has yet to be proven. Joint denervation may relieve joint pain showing that it is indeed articular nerves that are carrying pain impulses but denervation does not identify the precise source of the pain. It remains unclear which of the anatomical loci of pain generation are primary in OA and if sources of pain vary in different patients and in different joints.
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PMID:The anatomy of osteoarthritic joint pain. 2273 47


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