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

The contribution of the sensory and autonomic nervous system to experimentally induced tennis elbow or lateral epicondylalgia was investigated by analyses of the release of neuropeptides from sensory (substance P, SP, neurokinin A, NKA, calcitonin gene-related peptide, CGRP) and sympathetic (neuropeptide Y, NPY) nerves. SP, CGRP, NKA, NPY-like immunoreactivity (-LI) was studied in rats cerebrospinal fluid (CSF), plasma and perfusates (PF) from the enthesis of the extensor carpi radialis brevis (ECRB) of the right elbow at 2, 6 and 24 h following 0.01 ml injection of either complete Freund adjuvans (FA) or 2% Carrageenan (CAR). The control group was injected with 0.01 ml saline. In general the changes of neuropeptide-LI in the CSF and plasma were similar for both treated groups compared with the controls, but they were more pronounced in the FA group than the CAR. SP-, NKA-, CGRP- and NPY-LI were significantly increased to a similar degree in the perfusates of the ECRBs of the treated groups with a greater increase in SP-LI in the FA than the CAR group compared with controls. When comparing the neuropeptide-LI in the CSF, plasma and PF between the 2 treated groups, there were thus few differences found. Generally a unilateral injection with either FA or CAR into the rat ECRB induced a similar alteration in the concentration of SP-, NKA-, CGRP- and NPY-LI in the CSF, plasma and PF at 2, 6 and 24 h following injection. However, the most pronounced changes in neuropeptide-LI occurred locally in the elbow ECRBs PF in both treated groups.
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PMID:An experimental model of tennis elbow in rats: a study of the contribution of the nervous system. 1956 22

With use of immunohistochemistry and antibodies to substance P and calcitonin gene-related peptide, nerve fibers showing substance P-like and calcitonin gene-related peptide-like immunoreactivity were demonstrated at the origin of the extensor carpi radialis brevis muscle in patients with tennis elbow (n = 6) and in healthy controls (n = 6). The nerve fibers were distributed in association with a subpopulation of small blood vessels and in nerve bundles but were not distributed in the tunica media-adventitia junction of the arterioles. There were no inflammatory-cell infiltrates and few solitary mast cells. The present study gives further evidence to previous suggestions that tennis elbow is not an inflammatory process in the sense of involving inflammatory cells. Frequent mechanical involvement affects sensory innervation, and substance P and calcitonin gene-related peptide may have various important efferent effects, including microvascular leakage and local edema formation; therefore, the observations from this study constitute a morphological substrate for possible effects of substance P and calcitonin gene-related peptide at the origin of the extensor carpi radialis brevis muscle.
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PMID:Substance P and calcitonin gene-related peptide expression at the extensor carpi radialis brevis muscle origin: implications for the etiology of tennis elbow. 1045 62

By using immunohistochemistry and antibodies to a general nerve marker, protein gene product (PGP) 9.5, the overall innervation at the extensor carpi radialis brevis (ECRB) muscle origin was investigated in patients with tennis elbow and in healthy controls. The autonomic innervation was studied by using antibodies to neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). The sensory innervation was visualized by using antibodies to substance P and calcitonin gene-related peptide. PGP 9.5 immunoreactions were detected in association with small blood vessels and arteries and within nerve bundles. There was, however, heterogeneity in the perivascular nerve fiber distribution since some blood vessels exhibited a high degree of PGP 9.5 innervation and some negligible or no such innervation at all. There was marked TH/NPY innervation in the walls of a subpopulation of the arteries, basically no VIP-containing nerves, and sensory innervation restricted to the small blood vessels. These observations show that the ECRB muscle origin is supplied with heterogeneously distributed sympathetic and sensory innervations and, furthermore, that there appears to be an imbalance between the vasoconstrictor and vasodilator innervations along the vascular tree in this region.
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PMID:Sympathetic and sensory innervations are heterogeneously distributed in relation to the blood vessels at the extensor carpi radialis brevis muscle origin of man. 1046 Sep 73

To reveal whether neuropeptides and cytokines affect the pathogenesis of tennis elbow, expressions of substance P, calcitonin gene-related peptide, interleukin 1 alpha, and transforming growth factor beta1 at the origin of the extensor carpi radialis brevis muscle were investigated in patients with tennis elbow (n = 10). Innervation in the origin was determined with use of the protein gene product 9.5. Substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity were observed in the nerve fibers around small vessels without apparent infiltration of inflammatory cells. Cells showing positive interleukin 1 alpha or transforming growth factor beta1 immunoreactivity were noted in small vessels and the dense collagen meshwork in 5 of 10 cases. The results suggested that these neuropeptides and cytokines might promote inflammation and stimulate proliferation and matrix synthesis of fibroblasts, contributing to the pathology of tennis elbow.
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PMID:Expression of neuropeptides and cytokines at the extensor carpi radialis brevis muscle origin. 1246 81

There is no information on the sensory innervation at the flexor muscle origin at the medial epicondyle of the humerus and it is not known if substance P receptors (Neurokinin 1-receptors, NK1-R) are present in tendon insertions in general. In the present investigation, we have studied the muscle origin in patients suffering from medial epicondylalgia and tennis elbow. Immunohistochemistry and antibodies to substance P (SP) and CGRP as well as the general nerve marker PGP 9.5 were used. Specific immunoreactions were observed in nerve bundles and as free nerve fibers. The immunoreactive structures were partly seen in association with some of the blood vessels. The observations constitute a morphological correlate for the occurrence of nerve mediated effects in this region. By using immunohistochemistry and antibodies to NK1-R, the distribution of this receptor was studied at the insertion of the proximal tendon of the extensor carpi radialis brevis muscle at the lateral epicondyle. Specific immunoreactions were seen as varicose fibers occurring as single fibers or grouped into bundles, indicating that SP has effects in the nerves in this region. The results give further evidence for a possible neurogenic involvement in the pathophysiology of tennis elbow and in medial epicondylalgia.
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PMID:Neurokinin 1-receptors and sensory neuropeptides in tendon insertions at the medial and lateral epicondyles of the humerus. Studies on tennis elbow and medial epicondylalgia. 1501 91

Tennis elbow defines a condition of varying degrees of pain or point tenderness on or near the lateral epicondyle. It is prevalent in individuals who perform a combination of forceful and repetitive activities including athletes and wheelchair users. The most common work-related disorder at the elbow is tennis elbow. Histopathological findings indicate that tennis elbow is a degenerative condition, called tendinosis, of the common extensor tendon, with the extensor carpi radialis brevis tendon more commonly implicated as the primary location of tendinosis. Despite the absence of inflammation, patients with tennis elbow still present with pain. Neurochemicals including glutamate, substance P, and calcitonin gene-related peptide have been identified in patients with chronic tennis elbow and in animal models of tendinopathy. Their presence provides an alternative mechanism for pain mediation. Based on what is known about tissue changes within chronic tendinopathies, implications for therapy including examination and interventions are discussed.
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PMID:Tennis elbow: blending basic science with clinical practice. 1671 62

Application of extracorporeal shockwaves to the musculoskeletal system can induce long-term analgesia in the treatment of chronic painful diseases such as calcifying tendonitis of the shoulder, tennis elbow and chronic plantar fasciitis. However, the molecular and cellular mechanisms underlying this phenomenon are largely unknown. Recently it was shown that application of extracorporeal shockwaves to the distal femur of rabbits can lead to reduced concentration of substance P in the shockwaves' focal zone. In the present study we investigated the impact of extracorporeal shockwaves on the production of substance P within dorsal root ganglia in vivo. High-energy shockwaves were applied to the ventral side of the right distal femur of rabbits. After six weeks, the dorsal root ganglia L5 to L7 were investigated with high-precision design-based stereology. The application of extracorporeal shockwaves caused a statistically significant decrease in the mean number of neurons immunoreactive for substance P within the dorsal root ganglion L5 of the treated side compared with the untreated side, without affecting the total number of neurons within this dorsal root ganglion. No effect was observed in the dorsal root ganglia L6 and L7, respectively. These data might further contribute to our understanding of the molecular and cellular mechanisms in the induction of long-term analgesia by extracorporeal shockwave application to the musculoskeletal system.
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PMID:Extracorporeal shockwave application to the distal femur of rabbits diminishes the number of neurons immunoreactive for substance P in dorsal root ganglia L5. 1837 41

Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.
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PMID:Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow. 2765 44