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)

Studies of regional cerebral blood flow in migraine with aura have shown that the aura phase is associated with hypoperfusion in the cortical area which relates topographically to the clinical symptoms. Thus, the previously hypoperfused area becomes hyperperfused. However, there is no strict association between hyperperfusion and headache. The mode of hypoperfusion propagation recalls the circulatory manifestations of experimental cortical spreading depression. In addition, there are no focal cerebral blood flow abnormalities in migraine without aura. During the headache phase of migraine, dilation of both the large extra- and intracranial arteries takes place. A bulk of biochemical evidence has suggested that the pain in migraine is caused by blood vessels which are dilated and sensitized by circulating pain-producing substances e.g. bradykinin, serotonin and histamine (sterile inflammation). Recently, perivascular trigeminal fibres (trigeminovascular system) which, when stimulated, release sensory peptides (substance P and the calcitonin gene-related peptide) capable of provoking marked vasodilation and plasma extravasation (neurogenic inflammation) have been identified. Thus, the activation of the trigeminovascular system is probably involved in the vasodilatative and nociceptive phenomena of the migraine attack. The finding of a reduced endorphinergic brain tonus in migraine patients supports the hypothesis of a central nociceptive derangement in migraine. Nonetheless, the exact relationship between vasodilation and headache remains to be defined. However, the potent antimigraine effectiveness of sumatriptan--an agonist of the serotonin receptors which selectively constricts dilated arteries during the migraine attack--once again stresses the fact that serotonin is probably the crucial factor in the link between vasodilation and headache.
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PMID:[The pathogenetic bases of hemicrania]. 129 98

Aging of cat tooth pulp nerves involves ultrastructural changes, and changes in the expression of some neuropeptides and in the expression of the receptor for nerve growth factor. Electron microscopy of old pulps demonstrates loss and degeneration of unmyelinated and myelinated axons, as well as demyelination. Immunohistochemical findings show a marked age-related decrease in pulpal calcitonin-gene related peptide- and substance P-like immunoreactivity, and a reduction in nerve growth factor receptor-like immunoreactivity. Changes in neuropeptide expression are not entirely due to loss of nerve fibers, since most aging pulps contain nerve growth factor receptor-positive fibers which lack neuropeptide-like immunoreactivity. The changes reported here parallel the observation that there is an age-related reduction in sensitivity to pulpal stimulation, but may also contribute to the development of oral sensory phenomena such as neuropathic pain. Moreover, the senescent transformation of pulpal nerves probably affects hemoregulation of the pulp, and may thus have consequences for pulpal extraneuronal tissue.
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PMID:Changes in pulpal nerves with aging. 132 1

The local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
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PMID:Local motor responses to bradykinin and bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) in the guinea-pig isolated renal pelvis and ureter. 133 50

We evaluated the effect of intrathecal (i.t.) capsaicin (CAP) and the NK-1 selective non-peptidic antagonist, CP,96-345, on the thermal hyperalgesia ordinarily observed after unilateral partial ligation of the sciatic nerve in rats. CAP was injected i.t. 2 days after constriction injury. Seven days after partial ligation, the levels of substance P (sP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were the same in the left and right dorsal horns of the lesioned rats which were injected with vehicle (VEH). CAP (75 micrograms/15 microliters of 20% 2-hydroxypropyl-beta-cyclodextrin) resulted in an equal reduction (40-50%) in the dorsal horn levels of sP and CGRP, but not VIP. After 7 days, i.t. CAP increased the paw withdrawal latency (PWL) of the non-injured hind paw. In contrast, there was no change in the PWL of the injured paw when compared to that of VEH-treated animals. Thus, CAP did not abolish the hyperalgesic state. We concluded that the thermal hyperalgesia after sciatic nerve constriction injury is not mediated by CAP-sensitive C fibers. CP,96-345 given i.t. at a dose which is physiologically active (400 micrograms) had little effect on the thermal response latency of either the normal or hyperesthetic paw. This provides further evidence that neither the normal pain response nor hyperalgesic state is dependent upon a dorsal horn action of sP.
Pain 1992 Dec
PMID:Effects of intrathecal capsaicin and an NK-1 antagonist, CP,96-345, on the thermal hyperalgesia observed following unilateral constriction of the sciatic nerve in the rat. 133 98

The analgesic action of calcitonin (0.25 MRC units.kg-1) injected into lateral cerebral ventricle was investigated in rats. The pain threshold was evaluated by the tail-flick test. The influences of icv naloxone 5 micrograms/rat, a blocker of opiate receptor, on the analgesic action of calcitonin were observed. The results showed that icv calcitonin produced a significant analgesic action, which was reversed by naloxone. While the pain threshold was raised by calcitonin, the contents of central monoamines (5-HT, NE, DA) in brain (diencephalon, brain stem) were examined by fluorophotometry, which were increased remarkably. It is suggested that calcitonin-induced analgesia is related to the opiate receptors and the contents of 5-HT, NE, and DA in CNS.
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PMID:[Central analgesic action of calcitonin and its relationship with central monoamine transmitters]. 135 Aug 81

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.
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PMID:Changes in peptidergic innervation in chronic pancreatitis. 137 38

Increases in neuronal activity in response to tissue injury lead to changes in gene expression and prolonged changes in the nervous system. These functional changes appear to contribute to the hyperalgesia and spontaneous pain associated with tissue injury. This activity-dependent plasticity involves neuropeptides, such as dynorphin, substance P and calcitonin gene-related peptide, and excitatory amino acids, such as NMDA, which are chemical mediators involved in nociceptive processing. Unilateral inflammation in the hindpaw of the rat results in an increase in the expression of preprodynorphin and preproenkephalin mRNA in the spinal cord, which parallels the behavioral hyperalgesia associated with the inflammation. Cellular intermediate-early genes, such as c-fos, are also expressed in spinal cord neurons following inflammation and activation of nociceptors. Peripheral inflammation results in an enlargement of the receptive fields of many of these neurons. Dynorphin applied to the spinal cord also induces an enlargement of receptive fields. NMDA antagonists block the hyperexcitability produced by inflammation. A model has been proposed in which dynorphin, substance P and calcitonin gene-related peptide enhance excitability at NMDA receptor sites, leading first to dorsal horn hyperexcitability and then to excessive depolarization and excitotoxicity.
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PMID:Activity-dependent neuronal plasticity following tissue injury and inflammation. 137 25

Rats exposed to a cold environment (4 degrees C) for 30 min every 1 h during the day and at night show a gradual decrease in the nociceptive threshold for pressure stimulation. Such hyperalgesia, referred to as repeated cold stress (RCS)-induced hyperalgesia, is stable for at least 4 h and maintained for 3 days only by exposing to cold overnight; thus, no adaptation to RCS is apparent. Hyperalgesia gradually returns over 4 days after cold exposure ceases. To determine whether three neuropeptides, substance P (SP), calcitonin gene-related peptide (CGRP) and galanin (GAL), which are present in the superficial dorsal horn including primary afferent terminals, would be responsible for RCS-induced hyperalgesia, we examined the effects of intrathecal injections of their antibodies (used as inhibitors of neuropeptide-mediated synaptic transmission) on the nociceptive threshold of RCS rats, and compared this with the antibody effect on carrageenan-induced hyperalgesia. An intrathecal injection of anti-SP antibody significantly inhibited the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia, and slightly increased the nociceptive threshold of non-RCS rats. Anti-CGRP antibody produced an improvement in the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia without having an effect on the nociceptive threshold of non-RCS rats. Although anti-GAL antibody significantly inhibited carrageenan-induced hyperalgesia, it did not affect the nociceptive threshold of RCS and non-RCS rats. The present results suggest that enhancement of synaptic transmission mediated by SP and CGRP, but not GAL, in the spinal dorsal horn is, at least in part, involved in RCS-induced hyperalgesia.
Pain 1992 May
PMID:Effects of intrathecal antibodies to substance P, calcitonin gene-related peptide and galanin on repeated cold stress-induced hyperalgesia: comparison with carrageenan-induced hyperalgesia. 137 88

The effects of an experimentally induced arthritis on immunoreactivity of putative primary afferents neurotransmitter/neuromodulators were examined. Immunoreactive staining for substance P (SP), calcitonin gene-related peptide (CGRP) and glutamate (Glu) in the monkey dorsal horn was examined following inflammation of one knee joint induced by injection of 5% kaolin and 5% carrageenan. Spinal cords were examined at different time periods after induction of arthritis (2.5, 4, 6 and 8 h). Side to side differences in immunoreactivity were determined by a computer assisted quantitation system. A significant overall decrease in immunoreactivity of the lumbar versus the cervical dorsal horn was found for SP. The decrease for SP showed maximal changes of 68.3% at 4 h and 54.7% at 6 h. Immunoreactivity for CGRP was decreased 31.5% at 8 h and variable at other time points. Immunoreactivity for Glu, showed an ipsilateral increase of 31.4% at 4 h, 33.7% at 6 h, 39.9% at 8 h and a significant effect for lumbar versus cervical. Repetitive peripheral stimulation of the joint was shown to be important for changes in SP and Glu immunoreactivity. Without frequent peripheral stimulation in the early stages of the development of arthritis, SP showed no quantitative side to side differences. Increases in Glu immunoreactivity were present but not as prominent with minimal joint manipulation. These studies suggest that Glu may be involved in the aching pain of inflammation at rest whereas SP, CGRP and Glu may mediate pain induced by joint movement.
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PMID:Neural changes in acute arthritis in monkeys. III. Changes in substance P, calcitonin gene-related peptide and glutamate in the dorsal horn of the spinal cord. 137 98

Intramuscular hemangiomas are idiopathic lesions which are either tumoral or developmental in origin. A close association of abnormal blood vessels with nerve fibers is found and may suggest that nerves have a primary inciting role in the development of these lesions. In the current study, the number of nerve fibers in different zones around the tumors, as well as the type of neuropeptides present in these fibers, was quantitatively assessed by computer-assisted image analysis of immunohistochemical staining of histological slides. The number of nerve fibers as determined by positive staining by anti-protein S-100 antibodies was found to be elevated in the immediate vicinity of the abnormal blood vessels. The density of the nerve fibers rapidly declined with increasing distance from the hemangiomas, reaching normal values at distances of over 2 mm. Furthermore, hemangiomas contain a significantly higher number of calcitonin gene-related peptide (CGRP), substance P, and Met-enkephalin-positive fibers. The most significant rise in number is that of CGRP-positive fibers. This neuropeptide is a known mitogen, which could be responsible for the growth of the hemangiomatous blood vessels. Substance P is a nociceptive neurotransmitter and its presence can explain the pain which often accompanies even tiny intramuscular hemangiomas.
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PMID:Neuropeptidergic innervation of intramuscular hemangiomas. 137 96


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