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)

Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.
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PMID:Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord. 128 May 19

Neuropeptide FF (NPFF) is a mammalian FMRFamide-like octapeptide with antiopioid properties that inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, a series of three experiments was carried out to investigate the interactions between opioid receptor stimulation and antiopioid systems. First, by using in vitro superfusion system with rat spinal cord slices, we showed that morphine stimulated NPFF release in a dose-dependent manner. The stimulating effect which was observed with morphine concentrations as low as 100 fM reached a maximum at 0.1 nM, then decreased and was ineffective at 10 microM. The morphine-induced release of NPFF was abolished by naloxone (1 microM) but unaltered by tetrodotoxin. Second, by an in vivo approach, we showed that a single heroin administration (2.5 mg/kg, s.c.) elicited in 30 min a drastic drop (38%) in spinal NPFF content. In a third experiment, we evaluated the capacity of naloxone in revealing an antiopioid component associated with opioid receptor stimulation. The administration of naloxone (1 mg/kg, s.c..) 25 min following that of heroin (2.5 mg/kg, s.c.) not only abolished the heroin-induced increase of tail-flick latency, but also lowered it under the basal value by 30%. These results indicate that opioid receptor stimulation activates both pain inhibitory and pain facilitatory systems in which NPFF may play a significant role and that opiate-induced analgesia is always partly masked.
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PMID:Simultaneous activation of spinal antiopioid system (neuropeptide FF) and pain facilitatory circuitry by stimulation of opioid receptors in rats. 862 8

Neuropeptide FF (NPFF) and neuropeptide AF (NPAF) are two mammalian amidated neuropeptides which are highly concentrated in the posterior pituitary, spinal cord, hypothalamus and medulla. One precursor protein has been identified in mouse, rat, bovine and human brain. The precursor contains a single copy of both peptides, followed by a glycine residues necessary for amidation and flanked by basic residues necessary for processing by enzymes. In the brain, NPFF-like immunoreactive neurons are found in the hypothalamus and medulla. These systems may be associated with observed effects of NPFF on memory and autonomic regulation, respectively. A hypothalamo-pituitary pathway may be involved in neuroendocrine regulation. This is supported by lack of NPFF in the pituitary gland of vasopressin-deficient Brattleboro rats. It is also possible that NPFF acts as a hormone, as it has been detected in human plasma. The spinal cord contains an intrinsic NPFF-ir neuron system, with cell bodies in the dorsal horn and around the central canal. Nerve terminals are highly concentrated in the superficial laminae of the dorsal horn, where NPFF-immunoreactivity can be released by, e.g., potassium and substance P. One specific high-affinity binding site, distinct from binding sites for other peptides, has been characterized in the rat and human brain and spinal cord. The NPFF receptor appears to be coupled to a G-protein, but details of the second messenger systems have not been clarified yet. Intracerebroventricular injection of NPFF induces a vigorous abstinence syndrome in morphine-tolerant rats. Although clear antiopioid-like effects of NPFF on pain have been observed, some studies have also demonstrated long-lasting analgesic effects. These findings and the observed increase in NPFF-immunoreactivity in the cerebrospinal fluid during development of opiate tolerance render NPFF an interesting and challenging target of investigation.
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PMID:Neuropeptide FF, a mammalian neuropeptide with multiple functions. 880 17

Neuropeptide FF (NPFF) is a neuropeptide with some antiopioid characters found in several mammalian species. In human brain it might be an important pain-regulating peptide. Using a specific and sensitive radioimmunoassay we found a mean concentration of NPFF in human cerebrospinal fluid (CSF) of healthy volunteers of 1.6 +/- 1.1 pg/ml (n = 19) and in chronic pain (CPD) patients of 1.4 +/- 1.2 pg/ml (n = 16). The NPFF concentrations in CSF and plasma did not correlate. There was no difference in the NPFF concentrations in CSF and plasma between CPD patients and healthy controls. NPFF in CPD patients did not correlate significally with any pain characteristic. This study provides evidence for the presence of NPFF in human brain, but does not support the hypothesis that chronic pain is a consequence of elevated production of NPFF.
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PMID:Neuropeptide FF-like immunoreactivity in human cerebrospinal fluid of chronic pain patients and healthy controls. 935 47

The effect of neuropeptide FF in the periaqueductal gray on pain behaviour was studied in rats with a chronic neuropathy induced by unilateral ligation of two spinal nerves. Neuropeptide FF produced in a non-monotonic fashion a significant attenuation of tactile allodynia. The antiallodynic effect was not significantly modulated by naloxone administered systemically or intracerebrally. The dose of neuropeptide FF producing a significant antiallodynic effect was not antinociceptive in a test of mechanical or thermal nociception. The thermal antinociceptive effect induced by morphine administered in the periaqueductal gray was significantly attenuated by neuropeptide FF, whereas that induced by systemically administered morphine was not. The interaction of neuropeptide FF with intracerebrally or systemically administered morphine in a test of tactile allodynia was not significant. The results indicate that neuropeptide FF in the periaqueductal gray may produce a selective attenuation of tactile allodynia in neuropathic rats. This antiallodynic effect is at least partly independent of naloxone-sensitive opioid receptors. Furthermore, neuropeptide FF in the periaqueductal gray attenuates antinociception induced by intracerebrally but not systemically administered morphine.
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PMID:A differential modulation of allodynia, hyperalgesia and nociception by neuropeptide FF in the periaqueductal gray of neuropathic rats: interactions with morphine and naloxone. 969 64

The modulatory effects of 1DMe (d-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an agonist of Neuropeptide FF (NPFF) receptors, on opioid antinociceptive activity have been compared in naive and tolerant mice in the tail-flick and the hot-plate tests. In naive mice, 1DMe alone had no effect on pain threshold but decreased dose-dependently (3-22 nmol) the analgesic activity of morphine in both tests. In tolerant mice, injections of 60-fold lower doses of 1DMe (0.05-0.5 nmol) reverse morphine-induced analgesia in the tail-flick test but this anti-opioid effect was no longer observed with the highest doses of 1DMe tested (3-22 nmol). In the hot-plate test, the anti-opioid action of 1DMe was not detected, whatever doses tested. Neither the NPFF-like immunoreactivity content of spinal cord and of olfactory bulbs, nor the density of NPFF receptors in olfactory bulbs, were altered. These results indicate that a chronic morphine treatment modifies the pharmacological properties of NPFF but the type of pain test is crucial in determining NPFF effects.
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PMID:Anti-opioid efficacy of neuropeptide FF in morphine-tolerant mice. 976 58

Neuropeptides FF (NPFF), AF (NPAF), and SF (NPSF) are homologous amidated peptides that were originally identified on the basis of similarity to the molluscan neuropeptide FMRF-amide. They have been hypothesized to have wide-ranging functions in the mammalian central nervous system, including pain modulation, opiate function, cardiovascular regulation, and neuroendocrine function. We have cloned the NPFF gene from human, bovine, rat, and mouse, and show that the precursor mRNA encodes for all three of the biochemically identified peptides (NPFF, NPAF, and NPSF). We demonstrate that NPFF precursor mRNA expression by Northern analysis and map sites of expression by in situ hybridization. We confirm the validity of the in situ hybridization by showing that its distribution in the brain and spinal cord matches the distribution of NPFF and NPSF immunoreactivity. We go on to show that the mRNA levels (as measured by in situ hybridization) in the spinal cord can be up-regulated by a model for inflammatory pain (carrageenan injection), but not by a model for neuropathic pain (lumbar nerve ligation). Our results confirm the evolutionary conservation of NPFF, NPAF, and NPSF neuropeptide expression in mammalian brain. They also provide a context for the interpretation of the pain-sensitizing effects of injections of these peptides that have been previously reported. Our results support a model for the role of these peptides in pain regulation at the level of the spinal cord.
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PMID:Gene for pain modulatory neuropeptide NPFF: induction in spinal cord by noxious stimuli. 1022 May 58

Neuropeptide FF (NPFF) and the related longer peptide neuropeptide AF (NPAF) derive from a single gene in several mammalian species. The gene product is expressed mainly in the CNS, where the posterior pituitary and dorsal spinal cord contain the highest concentrations. Evidence from biochemical and immunohistochemical studies combined with in situ hybridization using NPFF gene-specific probes suggest that all NPFF-like peptides may not derive from the characterized NPFF gene, but that other genes can exist which give rise to related peptides. Intraventricular NPFF exerts antiopioid effects, but intrathecal NPFF potentiates the analgesic effects of morphine. NPFF mRNA expression is upregulated in the dorsal horn of the spinal cord after carrageenan-induced inflammation in the hind paw of the rat, but not in the neuropathic pain model induced by ligation of the spinal roots. NPFF produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem stimulation in the spinal cord during inflammation, and this effect is independent of naloxone-sensitive opioid receptors. In neuropathic animals, NPFF injected into the periaqueductal grey produces a significant attenuation of tactile allodynia, which is not modulated by naloxone. NPFF thus modulates pain sensation and morphine analgesia under normal and pathological conditions through both spinal and brain mechanisms.
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PMID:Neuropeptide FF and modulation of pain. 1061 11

Opiate tolerance and dependence are major clinical and social problems. The anti-opiate neuropeptides FF and AF (NPFF and NPAF) have been implicated in pain modulation as well as in opioid tolerance and may play a critical role in this process, although their mechanism of action has remained unknown. Here we describe a cDNA encoding a novel neuropeptide Y-like human orphan G protein-coupled receptor (GPCR), referred to as HLWAR77 for which NPAF and NPFF have high affinity. Cells transiently or stably expressing HLWAR77 bind and respond in a concentration-dependent manner to NPAF and NPFF and are also weakly activated by FMRF-amide (Phe-Met-Arg-Phe-amide) and a variety of related peptides. The high affinity and potency of human NPFF and human NPAF for HLWAR77 strongly suggest that these are the cognate ligands for this receptor. Expression of HLWAR77 was demonstrated in brain regions associated with opiate activity, consistent with the pain-modulating activity of these peptides, whereas the expression in adipose tissue suggests other physiological and pathophysiological activities for FMRF-amide neuropeptides. The discovery that the anti-opiate neuropeptides are the endogenous ligands for HLWAR77 will aid in defining the physiological role(s) of these ligands and facilitate the identification of receptor agonists and antagonists.
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PMID:Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor. 1085 Dec 42

This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) to modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(n.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH(2)), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperitoneal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-dependent antinociception not reversed by naloxone, an opioid antagonist, but inhibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c.v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothermia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions and could modulate pain transmission independently of opioids.
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PMID:Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia. 1103 7


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