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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased voltage-gated sodium channel activity may contribute to the hyperexcitability of sensory neurons in inflammatory and neuropathic pain states. We examined the levels of the transcript encoding the tetrodotoxin-resistant sodium channel SNS in dorsal root ganglion neurons in a range of inflammatory and neuropathic pain models in the rat. Local Freund's adjuvant or systemic nerve growth factor-induced inflammation did not substantially alter the total levels of SNS mRNA. When NGF-treated adult rat DRG neurons in vitro were compared with NGF-depleted control neurons, SNS total mRNA levels and the levels of membrane-associated immunoreactive SNS showed a small increase (17 and 25%, respectively), while CGRP levels increased fourfold. SNS expression is thus little dependent on NGF even though SNS transcript levels dropped by more than 60% 7-14 days after axotomy. In the streptozotocin diabetic rat SNS levels fell 25%, while in several manipulations of the L5/6 tight nerve ligation rat neuropathic pain model, SNS levels fell 40-80% in rat strains that are either susceptible or relatively resistant to the development of allodynia. Increased expression of SNS mRNA is thus unlikely to underlie sensory neuron hyperexcitability associated with inflammation, while lowered SNS transcript levels are associated with peripheral nerve damage.
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PMID:Regulation of expression of the sensory neuron-specific sodium channel SNS in inflammatory and neuropathic pain. 953 81

The aim of this investigation was to determine the temporal effect of an intra-articular injection of capsaicin to the temporomandibular joint on the levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-ir) in the trigeminal ganglion of the rat. The temporomandibular joints of 26 adult female rats were injected on one side with capsaicin and contralaterally with a control vehicle. Another 8 animals served as an untreated control group and received no injections. Animals were sacrificed at time intervals of 4 hours, 48 hours, 10 days, and 21 days following treatment. The trigeminal ganglia were extirpated, and CGRP-ir levels were quantified using a radioimmunoassay. Results demonstrated that when the capsaicin-treated side and the vehicle-treated side were compared, CGRP-ir levels decreased initially at 4 hours and increased at 48 hours. At 10 days, CGRP-ir levels had again dropped below control levels, followed by an increase at 21 days. CGRP-ir levels for the first two time periods investigated, which simulate an acute inflammatory state, mimic results observed in studies using limb joints, while the other time periods, which represent an intermediate and a chronic condition, respectively, suggest a more complex interaction with capsaicin-sensitive primary afferents.
J Orofac Pain 1998
PMID:Capsaicin application to the temporomandibular joint alters calcitonin gene-related peptide levels in the trigeminal ganglion of the rat. 965 88

Membrane metalloendopeptidase EC 3.4.24.11 (Enkephalinase, neutral endopeptidase, NEP) is a cellular ectoenzyme, immunophenotypically identified as the leukocyte cluster of differentiation CD10 or CALLA (common acute lymphoblastic leukemia antigen). Immunological, biochemical and molecular biology techniques have identified tis cell membrane feature in various organs: brain, cardiovascular system, lung, placenta, kidney etc. The CD10 immunophenotype is a common feature of lymphoblasts in acute lymphoid leukemia not expressing the T- or B-markers. The enzymatic activity of CD10/NEP possibly influences normal lymphocyte ontogeny by proteolytic cleavage of the regulatory peptides. The substrates of CD10/NEP in the kidneys are (see the list of abbreviations) ANP, adrenomedullin and PAMP; in the brain, the substrates are enkephalins and oxytocin; in the lung, bombesin, BLP, GRP, neuromedin C, substance P and neurokinin A; in the cardiovascular system, angiotenisin II, bradykinin and CGRP; in the gut, VIP; on the neutrophil membrane, fMLP etc. Some substrates are not strictly tissue-specific, e.g. substance P. Preclinical and clinical trials explore possibilities of therapeutic application of the inhibitors of neutral endopeptidase, such as thiorphan in the management of pain, diarrhoea, depression, arterial hypertension and asthma. Other possibilities of application include the treatment of hyalinomembranous disease and prevention of neurotoxicosis in tetanus and botulism.
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PMID:[Membrane metalloendopeptidase (CD10/CALLA): distribution, physiologic and pathophysiologic functions and its inhibitors]. 974 92

A homozygous CGRP-/- mouse line was generated by the targeted disruption of exon 5 in the calcitonin/alphaCGRP gene using homologous recombination. The mutant mice lack alphaCGRP mRNA. Furthermore CGRP immunoreactivity almost completely disappears from the spinal cord and is not at all observed in spinal ganglia and muscle synapses. However, motor end plates were still detected by acetylcholinesterase staining. Antinociceptive behavior tested by the tail flick and hot plate tests did not significantly differ in mutant and wild-type mice, except when challenged by morphine. Paradoxically, morphine analgesia was reduced in mutant mice compared with controls in the tail flick test, but not in the hot plate test. Thus, alphaCGRP differentially modulates opiate pain pathways.
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PMID:Modulation of morphine analgesia in alphaCGRP mutant mice. 1020 59

1. Migraine headache pain is thought to result from an abnormal distention of intracranial, extracerebral blood vessels and the consequent activation of the trigeminal nervous system. Migraine is also often accompanied by extracranial sensory disturbances from facial tissues. These experiments investigate whether meningeal dilation produces central sensitization of neurones that receive convergent input from the face. 2. Single unit extracellular activity was recorded from the trigeminal nucleus caudalis of anaesthetized rats in response to either noxious stimulation of the dura mater, innocuous stimulation of the vibrissae or to a transient dilation of the meningeal vascular bed. 3. Rat alpha-CGRP (calcitonin gene-related peptide; 1 microg kg(-1), i.v.) caused a dilation of the middle meningeal artery and facilitated vibrissal responses by 36+/-7%. 4. The 5-HT1B/1D agonist, L-741,604 (3 mg kg(-1), i.v.), inhibited responses to noxious stimulation of the dura mater (16+/-7% of control) and, in a separate group of animals, blocked the CGRP-evoked facilitation of vibrissal responses. 5. L-741,604 (3 mg kg(-1), i.v.) also inhibited responses to innocuous stimulation of the vibrissa (14+/-10% of control) with neurones that received convergent input from the face and from the dura mater, but not with cells that received input only from the face (70+/-12% of control). 6. These data show that dilation of meningeal blood vessels causes a sensitization of central trigeminal neurones and a facilitation of facial sensory processing which was blocked by activation of pre-synaptic 5-HT1B/1D receptors. 7. Sustained dural blood vessel dilation during migraine may cause a sensitization of trigeminal neurones. This may underlie some of the symptoms of migraine, such as the headache pain and the extracranial allodynia. Inhibition of this central sensitization may therefore offer a novel strategy for the development of acute and/or prophylactic anti-migraine therapies.
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PMID:Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5-HT1B/1D agonist. 1021 43

The meninges of the brain are innervated by afferent nerve fibres containing SP and CGRP, two typical peptides found in sensory neurons. These fibres project to the trigeminal nuclear complex and the cervical dorsal horn. Discharge of the afferents may provide a physiological basis for some types of headaches. Considerable speculation surrounds the possible causes of meningeal afferent activation. Blood-borne substances released during subarachnoid haemorrhage are one possibility and there is a possibility that these also play a role in migraine. In the case of migraine, blood components, e.g. from platelets, cannot be excluded. To investigate the possible effects of platelets and plasma factors, the subarachnoid space of the rat was continuously perfused with artificial cerebrospinal fluid during extracellular recordings from single units of the caudal trigeminal nucleus. Washed and concentrated suspensions of adenosindiphosphate (ADP)--activated platelets and plasma, from which platelets had been removed--were introduced as a bolus into the continuous flow. Neurons in the caudal nucleus of the trigeminal complex receiving input from the meninges were stimulated. They did not respond to the activated platelet suspensions but showed intense responses to plasma. Plasma completely lost its ability to excite trigeminal neurons after heat inactivation (30 min, 56 degrees C). It is concluded that the complement system may be involved in the excitatory nociceptive effect of platelet-poor plasma.
Pain 1999 Jun
PMID:Nociceptive neurons in the rat caudal trigeminal nucleus respond to blood plasma perfusion of the subarachnoid space: the involvement of complement. 1043 15

Calcitonin gene-related peptide [CGRP]--a powerful vasodilator, is a 37 amino acid peptide that is find primarily in the central and peripheral nervous system. It affects the regulation of local blood flow, smooth muscle tone and glandular secretion. It is an endocrine regulator and in the lungs it also exerts a bronchoconstricting effect. CGRP has a proliferative effect on human endothelial cells. Therefore, it is important for the formation of new vessels, example, in ischemia, inflammations, and in the healing of wounds. Plasma levels of CGRP are increase in patients with chronic cardiac failure and sepsis, indicating that CGRP may be another important peptide in chronic illness. We have therefore measured the release of this peptide and another sensory peptide [Substance P (SP)]; a vasoconstrictor peptide [Endothelin (ET)]; and a perivascular peptide [Neuropeptide Y (NPY)], within 24 hours of injury, in the plasma of patients with soft tissue injury. Neuropeptides were measure by enzyme immunoassay technique. Median: (lower quartile-upper quartile) in pmol/L CGRP level was elevated in patients [50.37: (12.4-110.9)] compared to controls [13.9: (10.9-36.96)] p<0.05; Endothelin and NPY did not vary much between groups p=NS; ET: patients [8.7: (1.7-87.1), controls 8.8: (1.7-32.9)]; NPY: Patients [11.7: (10.5-14.99), controls 11: (10.3-12.8)]. SP was increase in patients [302.3: (79.9-707.3)], than controls [5.6: (3.2-36.6)] p<0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications), was measure (ng/L), and found to be slightly higher in patients (102: 25.5-223), than controls (91.8: 45.9-127). In summary, plasma levels of sensory peptides increased significantly, in patients with soft tissue injury, in contrast to vasocostrictor peptides that remained unchanged. These sensory peptides may yet be another group of neuromodulators playing a significant role in immune, pain, inflammatory and wound healing in soft tissue injury patients.
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PMID:Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury. 1050 54

Current theories propose that the primary dysfunction in migraine occurs within the CNS and that this evokes changes in blood vessels within pain-producing intracranial meningeal structures that give rise to headache pain. Migraine is now thought of as a neurovascular disorder. It has been proposed that genetic abnormalities may be responsible for altering the response threshold to migraine specific trigger factors in the brain of a migraineur compared to a normal individual. The exact nature of the central dysfunction that is produced in migraineurs is still not clear and may involve spreading depression-like phenomena and activation of brain stem monoaminergic nuclei that are part of the central autonomic, vascular and pain control centers. It is generally thought that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is a key mechanism underlying the generation of headache pain associated with migraine. This activation of the 'trigeminovascular system' is thought to cause the release of vasoactive sensory neuropeptides, especially CGRP, that increase the pain response. The activated trigeminal nerves convey nociceptive information to central neurons in the brain stem trigeminal sensory nuclei that in turn relay the pain signals to higher centers where headache pain is perceived. It has been hypothesized that these central neurons may become sensitized as a migraine attack progresses. The 'triptan' anti-migraine agents (e.g. sumatriptan, rizatriptan, zolmitriptan naratriptan) are serotonergic agonists that have been shown to act selectively by causing vasoconstriction through 5-HT1B receptors that are expressed in human intracranial arteries and by inhibiting nociceptive transmission through an action at 5-HT1D receptors on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brain stem sensory nuclei. These three complementary sites of action underlie the clinical effectiveness of the 5-HT1B/1D agonists against migraine headache pain and its associated symptoms.
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PMID:Pathophysiology of migraine--new insights. 1056 28

Cerebrospinal fluid (CSF) levels of calcitonin gene-related peptide-like activity (CGRP-LI), were determined in 35 patients with painful orthopaedic disorders and the activity was compared to that of 12 healthy controls without pain. Fourteen patients had pain from osteoarthritis of the hip or the knee, 11 had rhizopathic pain due to a herniated lumbar disc and 10 had pain from a hip fracture. In all patients, decreased CGRP-LI was observed in CSF compared to the controls. The lowest values were found in the patients with osteoarthritis, while there was less, but still significant, reduction of CGRP-LI in the patients with herniated lumbar disc and those with a hip fracture. In most of the patients, CGRP-LI was also analysed at a second lumbar puncture after operative treatment, when pain had subsided or was reduced. However, the CGRP-LI remained low after treatment, which may suggest the influence of factors other than pain.
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PMID:Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients. 1065 34

A possibly beneficial effect of spinal cord stimulation (SCS) on acute and chronic nociceptive pain is still a controversial issue. In the present experimental study, SCS was applied, with parameters similar to those used clinically, to awake but restrained rats submitted to intraplantar injection of carrageenan (CAR). The paw circumference and the threshold of paw withdrawal and/or vocalization to pressure, applied by a pair of strain gauge calibrated flat forceps to the paw, were determined before and after CAR injection. As controls, one group of rats was treated by CAR injection only; a second group was subjected to SCS after CAR injection; a third group was pretreated with SCS for 3 days before the injection; a fourth group subjected to SCS only. In the acute phase, 3 h after the injection, SCS enhanced the CAR-induced hyperalgesia and oedema. Conversely, in the subacute phase at day 3-5 after the injection, SCS suppressed the hyperalgesia which was, however, less marked than in the acute phase. However, in that phase, the oedema was still increased by SCS. Pretreatment by SCS influenced neither the natural time course of hyperalgesia nor that of oedema. Circumstantial evidence suggests that the oedema augmentation by SCS in the acute phase may be the result of enhanced vasodilatation with fluid extravasation, probably associated with peripheral release of several substances, such as CGRP. The concomitant increase of the hyperalgesia may reflect an enhanced release of substance P and 5-HT, both peripherally and in the dorsal horn. The attenuation of hyperalgesia in the subacute phase may be due to an inhibitory effect of SCS on A-fibre-mediated wide-dynamic-range neuronal hyperactivity, presumably involving GABAergic mechanisms. However, a direct suppressive effect on sensitized nociceptive-specific second-order neurons cannot be excluded. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
Eur J Pain 1999 Dec
PMID:Opposite effects of spinal cord stimulation in different phases of carrageenan-induced hyperalgesia. 1070 Mar 64


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