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)

There is increasing evidence that-back pain may originate from degenerated or damaged disks, even in the absence of disk herniation. For a study of the pattern of innervation in injured disks, the anterior part of the annulus fibrosus of a lumbar disk in 11 domestic pigs was incised with a scalpel through a retroperitoneal approach. The animals were killed 2 weeks, 1, 2, 3, and 5 months postoperatively, and the whole anterior annulus of each injured disk and corresponding tissue from intact animals were excised. Cryostat sections 20 microns thick were cut from the surface downward, fixed, and stained with different antisera. Antisera to neurofilament triplet protein (R39), protein gene product (PGP) 9.5 and synaptophysin were used as general neural markers. Antiserum to substance P (SP) and calcitonin gene-related peptide (CGRP) were used to localize nerves mainly of the sensory type, and C flanking peptide of neuropeptide Y (CPON) to visualize nerve fibers of the sympathetic type. It was observed that in the intact porcine disk, the outer and middle parts of the anterior annulus were innervated to a depth of 7 mm from the annular surface, but the innermost annular layers showed no immunoreactivity to any of the neural antibodies. Disk injury did not cause any major changes in the nerve topography of the wound area, even though there were granulation tissue and neovascularization in this area.
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PMID:Neural elements in the normal and experimentally injured porcine intervertebral disk. 753 35

The innervation of the human intervertebral disc was investigated by immunochemical methods. Immunoreactivity to the general nerve marker protein gene product (PGP 9.5) was found in the outer annulus fibrosus of 11 of 12 discs removed during anterior arthrodesis for back pain. PGP 9.5-immunoreactive fibres ran between and across the collagenous lamellae, both in association with blood vessels and distant from them, and extended at least 3 mm into the disc. No innervation was observed in the nucleus pulposus. Fine fibres (< 1 micron in diameter) immunoreactive to calcitonin gene-related peptide and substance P (neuropeptides located in sensory and possibly nociceptive nerves) were identified in eight and four of the annuli fibrosi, respectively. Nerve fibres immunoreactive to vasoactive intestinal peptide and to the c-flanking peptide of neuropeptide Y were found in the majority of specimens of annulus fibrosus that were examined.
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PMID:Neuropeptides in the human intervertebral disc. 816 90

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease.
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PMID:Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. 902 Apr 64

Topically applied capsaicin (CAS 404-86-4) induces the release of substance P, a neurotransmitter, from sensory C-fibres. In addition, there is a specific blockade of transport and de-novo synthesis of substance P. As a result, repeated applications of capsaicin bring about a long lasting desensitisation to pain (increase of pain threshold). The desensitising effect is fully reversible. The confirmed pharmacodynamic actions and a number of double-blind clinical studies indicate that local capsicum preparations are very suitable for the treatment of neuropathic pain or musculoskeletal disorders, with or without inflammatory components. In a double-blind, randomised parallel-group study a capsicum plaster was compared with a placebo for 3 weeks in 154 patients with non-specific back pain. Inclusion criteria were a history of back pain for a minimum period of 3 months and a degree of pain of 5 or more on an eleven grade visual analogue scale. The principal target variable consisted of the score of 3 combined pain scales. Secondary efficacy measures were tests of mobility, a disability index (in the context of Arhus low back rating scale) and global assessments by physicians and patients. For patients to be rated as responders their total pain score at the final examination after 3 weeks of treatment had to show a reduction by at least 30% of the baseline value. The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219). The sum of the 3 separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%; p = 0.002). Relatively slight improvements of the impaired mobility and the functional status are explained by the characteristics of the disorder treated. The efficacy ratings by observers and patients was definitely in favour of capsicum. Adverse effects--mostly harmless and resolving spontaneously--were reported by 15 patients in the capsicum group and by 9 in the placebo group. The tolerance ratings by investigators and patients were superior to the placebo product. This, however, partly is due to the local pharmacological actions of the drug. As in comparably positive randomised studies with capsaicin cream in patients with osteoarthritis or fibromyalgia it was shown that a capsicum plaster preparation can also be used to advantage in chronic non-specific back pain.
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PMID:Capsicum pain plaster in chronic non-specific low back pain. 1176 91

Facet joints are implicated as a major source of neck and low-back pain. Both cervical and lumbar facet syndromes have been described in the medical literature. Biomechanical studies have shown that lumbar and cervical facet-joint capsules can undergo high strains during spine-loading. Neuroanatomic studies have demonstrated free and encapsulated nerve endings in facet joints as well as nerves containing substance P and calcitonin gene-related peptide. Neurophysiologic studies have shown that facet-joint capsules contain low-threshold mechanoreceptors, mechanically sensitive nociceptors, and silent nociceptors. Inflammation leads to decreased thresholds of nerve endings in facet capsules as well as elevated baseline discharge rates. Recent biomechanical studies suggest that rear-end motor-vehicle impacts give rise to excessive deformation of the capsules of lower cervical facet joints. Still unresolved is whether this stretch is sufficient to activate nociceptors in the joint capsule. To answer this question, recent studies indicate that low stretch levels activate proprioceptors in the facet-joint capsule. Excessive capsule stretch activates nociceptors, leads to prolonged neural afterdischarges, and can cause damage to the capsule and to axons in the capsule. In instances in which a whiplash event is severe enough to injure the joint capsule, facet capsule overstretch is a possible cause of persistent neck pain.
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PMID:Pain generation in lumbar and cervical facet joints. 1659 46

The mechanism underlying discogenic low-back pain is unclear. It is difficult to explain this type of pain by the segmental innervation theory because the groin area is innervated by the genitofemoral or ilioinguinal nerves, which are the terminal branches of the L1 or L2 spinal nerves. Recently, some studies have indicated that sympathetic trunks are closely related to discogenic low-back pain. However, sympathetic trunk resection can severely affect the function of the abdominal organs and lower extremities and may cause retrograde ejaculation in human beings. This study was initiated to evaluate the role of selective transection of the L2 ramus of the nociceptive pathway in the lumbar intervertebral discs in rats, by using the fluorogold (FG) retrograde transport method and immunohistochemistry of substance P (SP). Of the FG-labeled neurons in the L2 and L5 dorsal root ganglia (DRGs), the cross-sectional area of the SP-immunoreactive (ir) neurons ranged from 210 to 1140 microm(2); the mean cross-sectional area was 652+/-320 microm(2). We demonstrated that FG-labeled SP-ir neurons in L2 DRGs decreased when FG was applied to the ventral or dorsal portions of L5-6 discs. The results indicated that the L2 ramus communicans played an important role in the afferent pathway of both the ventral and dorsal portions of the L5-6 disc. Nociceptive information from the L5-6 disc may be transmitted mainly by L2 DRG neurons through the L2 ramus communicans.
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PMID:Effect of the L2 ramus communicans on the nociceptive pathway in lumbar intervertebral discs in rats. 1824 22

Astronauts exposed to microgravity frequently report low back pain. This pain is described as moderate to severe in intensity. This condition warrants investigation as low back pain may hinder an astronaut's ability to perform challenging tasks by virtue of disruption of sleep and, subsequently, mental concentration. It is reported by astronauts that a "fetal tuck position" described as knees to chest position relieves back pain. It is possible that the pathogenesis of back pain in microgravity is discogenic (or mechanical) and somatic, referred from the sinuvertebral nerves due to excessive expansion of the lumbar intervertebral discs associated with reduction of gravitational compressive loads in space. The fetal tuck position may increase lumbar intervertebral disc hydrostatic pressure by flexion and transfer of spinal compressive forces toward the anterior region of the lumbar discs, subsequently reducing disc volume. Moreover, this position may reduce Type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus, and thus diminish low back pain perception. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate Type I and II mechanoreceptors. This neutralizes substance P in the spinal cord dorsal horn by increasing naturally occurring opioids such as enkephalins. Separately, other investigators have reported a higher incidence of herniated discs (HNP) in astronauts postflight. Further studies of countermeasures are recommended to prevent excessive spinal elongation and disc expansion, reduce low back pain in microgravity, and simulate 1-G disc homeostasis, which may also help prevent HNPs postflight.
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PMID:Pathophysiology of low back pain during exposure to microgravity. 1845 93

One minute downward pressure on the tip of any one of the front 3 teeth (1st incisor, 2nd incisor, and canine) at the right and left sides of the upper and lower jaw by a wooden toothpick induced temporary disappearance (20 min approximately 4 hours) of abnormally increased pain parameters (pain grading, Substance P, & TXB2), and cancer parameters (Telomere, Integrin alpha5beta1, Oncogene C-fos Ab2, etc. of Astrocytoma, Glioblastoma, squamous cell carcinoma of esophagus, adenocarcinoma of lung, breast cancer, adenocarcinoma of colon, prostate cancer). The effect included temporary disappearance of headache, toothache, chest and abdominal pain, and backache, often with improved memory & concentration. Since these beneficial changes resembled the effects of giving one optimal dose of DHEA, increase of DHEA was measured. Above mechanical stimulation of one of these front teeth increased abnormally reduced DHEA levels of less than 10 ng to norm1 100 approximately 130 ng BDORT units and normal cell (NC) telomeres from markedly reduced values to near normal values, and improved acetylcholine in the Hippocampus. Large organ representation areas for the Adrenal gland & Hippocampus may exist at these front teeth. This method can be used for emergency pain control and can explain the beneficial effect of bruxism and tooth brushing, through the increase of DHEA levels and activities of the Hippocampus by increasing Acetylcholine. Increasing NC telomere to optimally high level resulted in disappearance of pain and improvement or significant reduction of malignant tumor. Repeated daily press needle stimulation of True ST. 36 increased NC telomere 450-700 ng BDORT units. One optimal dose of DHEA increased NC telomere 525 ng DBORT units and eliminated the pain and abnormally increased cancer parameters; effect of one optimal dose lasted 0.5-11 months. One optimal dose of Boswellia Serrata or Astragalus not only increased NC telomere 650 ng BDORT units, eliminating pain and cancer parameters, but also reduced the size of the Astrocytoma grade I by 10-20% and the Glioblastoma by 15-90% in less than 2-6 months in some patients, as long as high NC telomere is maintained.
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PMID:Temporary anti-cancer & anti-pain effects of mechanical stimulation of any one of 3 front teeth (1st incisor, 2nd incisor, & canine) of right & left side of upper & lower jaws and their possible mechanism, & relatively long term disappearance of pain & cancer parameters by one optimal dose of DHEA, Astragalus, Boswellia Serrata, often with press needle stimulation of True ST. 36. 2034 85

Arthritis is characterized by pain and inflammation. Recently, attention has been focused on nerve-growth factor (NGF), a neurotrophin that is a key regulator of peripheral nociception because it mediates overexpression of proinflammatory neuron-derived molecules such as substance P, serotonin, and calcitonin gene-related peptide. Antibodies have been generated for NGF and its receptor that are effective in reducing pain in preclinical pain models, and clinical trials in patients with advanced knee and hip osteoarthritis and low-back pain. Results show pain reduction is rapid and sustained. Adverse events with anti-NGF included transient paraesthesia and edema, rapidly progressive OA, and, in a small number of patients treated with both anti-NGF and nonsteroidal anti-inflammatory drugs, osteonecrosis. Inhibition of the NGF-stimulated nociceptive pathway seems to be effective; however, the adverse effects require further investigation.
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PMID:Control of arthritis pain with anti-nerve-growth factor: risk and benefit. 2294 88

Chronic pain is a significant burden and much is attributed to back muscles. Back muscles and their associated fasciae make important and distinct contributions to back pain. Peptidergic nociceptors innervating these structures contribute to central transmission and pain modulation by peripheral and central actions. Plastic changes that augment and prolong pain are exhibited by neurons containing calcitonin gene-related peptide (CGRP) following muscle injury. Subpopulations of neurons containing this peptide have been identified in dorsal root ganglia but the distribution of their fibers in skeletal muscles and associated fasciae has not been fully documented. This study used multiple-labeling immunofluorescence and retrograde axonal tracing to identify dorsal root ganglion cells associated with muscle, and to characterize the distribution and density of their nerve fibers in mouse gastrocnemius and back muscles and in the thoracolumbar fascia. Most nerve fibers in these tissues contained CGRP and two major subpopulations of neurons were found: those containing CGRP and substance P (SP) and those containing CGRP but not SP. Innervation density was three times higher in the thoracolumbar fascia than in muscles of the back. These studies show mouse back and leg muscles are predominantly innervated by neurons containing CGRP, an important modulator of pain signal transmission. There are two distinct populations of neurons containing this peptide and their fibers were three times more densely distributed in the thoracolumbar fascia than back muscles.
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PMID:Sensory nerve fibers containing calcitonin gene-related peptide in gastrocnemius, latissimus dorsi and erector spinae muscles and thoracolumbar fascia in mice. 2568 18


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