Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two ganglionic cell groups, located close together and called the internal carotid ganglion, not described before in man, were demonstrated extradurally on the ventrolateral surface of the human internal carotid artery (ICA), where the greater superficial petrosal nerve is joined by the (greater) deep petrosal nerve to form the vidian nerve. The two ganglionic cell groups have fiber connections to the ICA, and consist of 50-70 cells each. By immunohistochemistry the majority of cells in one of the groups were shown to contain vasoactive intestinal polypeptide (VIP) and choline acetyltransferase (ChAT) indicating a parasympathetic function, whereas most cells in the other group contained substance P (SP) and possibly calcitonin gene-related peptide (CGRP), transmitters in pain fibers. Lateral to the intracavernous segment of ICA 10-150 scattered or aggregated VIP- and ChAT-positive cells were found, with fiber connections to the ophthalmic nerve, the ICA, the abducent nerve and the sphenopalatine ganglion. These cells may represent aberrant parasympathetic (sphenopalatine) ganglia, here referred to as cavernous ganglion. By radioimmunoassay substantial amounts of VIP, SP and CGRP were measured in both the extradural and the intracavernous segment of the ICA. Thus, the intracranial segment of the ICA is most likely innervated by parasympathetic and pain fibers from the internal carotid ganglion, sensory fibers from the ophthalmic division of the trigeminal ganglion, and parasympathetic fibers from the sphenopalatine and/or cavernous ganglion. Clinical implications for the activation of these nerves to cause pain, dilatation and edema in this segment of the ICA during attacks of cluster headache and painful ophthalmoplegic syndromes are discussed.
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PMID:Anatomical basis for a parasympathetic and sensory innervation of the intracranial segment of the internal carotid artery in man. Possible implication for vascular headache. 171 60

The effects of capsaicin injections into neonatal rats on the ultrastructure of the neonatal dorsal horn and on some biochemical and behavioral parameters in the adult were examined. Electron microscopic observations revealed degeneration and glial engulfment of boutons and umyelinated axons in the dorsal horn 2 and 6 h after neonatal subcutaneous capsaicin injections. Capsaicin treatment had no effect on the activities of glutamic acid decarboxylase and choline acetyltransferase in the dorsal horn. Results of substance P measurements in the CNS showed no effect of capsaicin administration on striatal, hypothalamic or nigral substance P content, whereas substance P levels in the dorsal horn of the spinal cord were reduced by half. The density of [3H]naloxone binding sites in the dorsal horn was significantly reduced, while the affinity was not affected. Capsaicin-treated animals showed significantly increased latencies to respond to a noxious thermal stimulus in both tail-flick and hot-plate tests. The results are discussed in relation to the current concepts of the involvement of substance P and opiate systems in nociception and the potential use of neonatal capsaicin as a selective neurotoxin for the elucidation of the spinal mechanisms of pain.
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PMID:Neurotoxic action of capsaicin on spinal substance P neurons. 615 57

The topographic location of the enzyme choline acetyltransferase (ChAT) has recently been determined within the human spinal cord. ChAT, which is regarded as a specific marker of cholinergic structures in nervous tissue, showed an area of high activity in the ventrolateral part of the ventral horn, probably related to motor neurons. In addition, an area of high ChAT activity was found in the apical part of the dorsal horn. As amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of the cortico-spinal tracts and the lower motor neurons, we considered it of value to investigate the involvement of spinal cholinergic structures in this disorder. Substance P is regarded as the transmitter of incoming pain signals to the dorsal horn of the spinal cord, a subject recently reviewed by Marx. As disturbed sensation of pain is not a symptom of ALS, there seemed reason to correlate the spinal concentration of this peptide with the activities of ChAT in ALS.
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PMID:Choline acetyltransferase and substance P-like immuno-reactivity in the human spinal cord: changes in amyotrophic lateral sclerosis. 618 25

The involvement of the hippocampal choline acetyltransferase (ChAT) activity in the response to tonic pain was investigated in rats injected with formalin, either 50 microliters 10% or 50 microliters 0.1%. Hippocampal ChAT activity was found to be reduced both 30 and 60 min after injection of the higher concentration of formalin but only 30 min after the lower one. Results indicate that the decrease in ChAT activity depends upon the presence of the nociceptive input rather than its magnitude. The hippocampal formation is involved in the specific behavioural response to pain, namely licking.
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PMID:Decrease of hippocampal choline acetyltransferase activity induced by formalin pain. 828 73

Cannabis has been used for centuries in the medicinal treatment of gastrointestinal disorders. Endogenous cannabinimimetic substances such as 2-arachidonylglycerol have been isolated from gut homogenates and CB1-cannabinoid binding sites have been identified in small intestine. In this study, CB1-cannabinoid receptors (CB1-R) were immunohistochemically localized within the enteric nervous system of the pig, an omnivorous species whose digestive tract is functionally similar to humans. Two anti-CB1-R antisera, raised against N-terminal epitopes in the human CB1-R, were employed to localize receptor immunoreactivity by secondary immunofluorescence. CB1-R immunoreactivity was observed in the myenteric and submucosal ganglionated plexuses of porcine ileum and colon. In the ileum, all CB1-R-immunoreactive neurons coexpressed immunoreactivity to the cholinergic marker, choline acetyltransferase (ChAT). CB1-R/ChAT-immunoreactive neurons appeared to be in close apposition to ileal Peyer's patches, submucosal blood vessels, and intestinal crypts. In the distal colon, CB1-R-immunoreactive neurons also expressed immunoreactivity to ChAT, albeit less frequently than in ileum. Immunoreactivity to vasoactive intestinal peptide or nitric oxide synthase was not colocalized in ileal or colonic CB1-R-immunoreactive neurons. These studies indicate that CB1-R are present in cholinergic neurons in the porcine enteric nervous system. The potential roles of these receptors in intestinal motility and epithelial transport, host defense and visceral pain transmission are discussed.
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PMID:Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. 1107 17

Opioid drugs have profound antidiarrheal and constipating actions in the intestinal tract and are effective in mitigating abdominal pain. Mediators of intestinal inflammation and allergy produce increased mucosal secretion, altered bowel motility and pain due to their ability to evoke enteric secretomotor reflexes through primary afferent neurons. In this study, the distribution of delta- and kappa-opioid receptor (DOR and KOR, respectively) immunoreactivities in chemically identified neurons of the porcine ileum was compared with that of the capsaicin-sensitive type 1 vanilloid receptor (VR1). DOR and VR1 immunoreactivities were observed to be highly localized in choline acetyltransferase (ChAT)- and calcitonin gene-related peptide (CGRP)-positive neurons and nerve fibers of the submucosal and myenteric plexuses and both receptors exhibited frequent colocalization. In the inner submucosal plexus, they also were colocalized in substance P (SP)-positive neurons. Neurons in the outer submucosal plexus expressed DOR immunoreactivity alone or in combination with VR1. KOR-immunoreactive neurons were found only in the myenteric plexus; these cells coexpressed immunoreactivity to ChAT, CGRP, vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS). In addition, some KOR-positive neurons coexpressed immunoreactivities to DOR and VR1. Based on their neurochemical coding, opioid and vanilloid receptor-immunoreactive neurons in the submucosal and myenteric plexuses may include primary afferents and constitute novel therapeutic targets for the palliation of painful intestinal inflammatory, hypersensitivity and dysmotility states.
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PMID:Chemical coding of neurons expressing delta- and kappa-opioid receptor and type I vanilloid receptor immunoreactivities in the porcine ileum. 1181 Mar 11

Cholinergic modulation of nociceptive transmission through both nicotinic and muscarinic receptors in the spinal cord represents an important mechanism in pain signaling. However, what neuronal elements release acetylcholine and how release might change in response to deafferentation are unclear. The present studies demonstrated Ca++- and K+-dependent release of [3H]-acetylcholine from slices of regional areas of rat spinal cord. That [3H]-acetylcholine was synthesized from [3H]-choline was demonstrated by the lack of [3H]-acetylcholine release following incubation with either the choline uptake inhibitor hemicholinium or the choline acetyltransferase inhibitor bromoacetylcholine. Rats treated neonatally with capsaicin or with spinal nerve ligation as adults showed a significantly decreased K+-stimulated release of [3H]-acetylcholine from dorsal horn but not ventral horn lumbar spinal cord slices. In rats subjected to dorsal rhizotomy, while basal release from lumbar dorsal spinal cord slices was reduced, K+-stimulated [3H]-acetylcholine release, while decreased, was not significantly different compared with controls. The data presented here show that there are regional differences in the release of acetylcholine from spinal cord and that this release can be modulated by chemical or surgical deafferentation. These results also indicate that the source of acetylcholine in the dorsal cord originates mainly from resident somata and their collaterals, interneurons and/or descending terminals, with only very minor contributions coming from primary afferents. The present data help to further elucidate the role of acetylcholine in spinal signaling, particularly with respect to the effects of nerve injury and nociceptive neurotransmission.
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PMID:The effects of chemical or surgical deafferentation on [3H]-acetylcholine release from rat spinal cord. 1616 86

The pathogenesis of the pain in patellar tendon tendinosis ("jumper's knee") is unclear. We have recently presented new information about the sensory nervous system in the human patellar tendon, but there is very little information regarding the possible occurrence of a cholinergic system in this tendon. In the present study, specimens of pain-free normal tendons and chronically painful tendinosis tendons were examined by different immunohistochemical and histochemical methods. Antibodies against the M(2) receptor, choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT) were applied, and staining for demonstration of activity of acetylcholinesterase (AChE) was also utilized. It was found that immunoreactions for the M(2) receptor could be detected intracellularly in both blood vessel cells and tenocytes, especially in tendinosis specimens. Furthermore, in the tendinosis specimens, some tenocytes were seen to exhibit immunoreaction for ChAT and VAChT. AChE reactions were seen in fine nerve fibers associated with small blood vessels in both the normal control tendons and the tendinosis tendons. The observations suggest that there is both a nerve related and a local cholinergic system in the human patellar tendon. As ChAT and VAChT immunoreactions were detected in tenocytes of tendinosis tendons, these cells might be a source of local acetylcholine (Ach) production. As both tenocytes and blood vessel cells were found to exhibit immunoreactions for the M(2) receptor, it is likely that both of these tissue cells may be influenced by ACh. Thus, in conclusion, there appears to be an upregulation of the cholinergic system, and an occurrence of autocrine/paracrine effects in this system, in the tendinosis patellar tendon.
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PMID:Immunohistochemical and histochemical findings favoring the occurrence of autocrine/paracrine as well as nerve-related cholinergic effects in chronic painful patellar tendon tendinosis. 1683 Mar 27

alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha9alpha10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of alpha9alpha10 nAChRs in the pathophysiology of peripheral nerve injury.
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PMID:Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. 1710 79

We have recently obtained evidence favoring the occurrence of an up-regulation of a non-neuronal cholinergic system in chronic painful patellar tendon tendinosis. It seems possible that this up-regulation to a certain degree may be involved in the manifestations of the disease. Today, there is a new, very successful, line of treatment of patellar tendinosis in the form of Doppler guided sclerosing injections. However, a few patients seem resistant to this therapy. Therefore, we have in this pilot study investigated biopsies from the patellar tendon of three such therapy-resistant patients, using immunohistochemistry. In situ hybridization was also applied. Comparisons were made with a material of specimens from both normal (n=16) and tendinosis (n=7) tendons, also previously examined. The study showed that there were extensive immunoreactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter, as well as for the M(2) muscarinic acetylcholine receptor, in the overwhelming majority of the tenocytes. The immunoreactions were more pronounced than those generally obtained in the tendinosis tissue of the previously studied patients and clearly more pronounced than those of patellar tendon tissue of controls. Also, for the first time, we here present findings of mRNA for ChAT within tenocytes. In conclusion, it appears as if there is an excessive local acetylcholine (ACh) production and an occurrence of marked ACh effects in cases of severe tendinosis. An excessive production of local ACh might be related to pain sensation and the processes that occur in tendinosis development, such as cell proliferation. Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis.
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PMID:Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study. 1728 83


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