Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.
 ...
PMID:Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. 1148 30

Neuropeptide FF (NPFF) is an endogenous anti-opioid peptide. NPFF could potentiate the naloxone-precipitated morphine withdrawal syndromes in morphine-dependent rats, indicating the possible involvement of the endogenous NPFF system in opioid analgesia and dependence. The present study was performed to examine the effects of dansyl-PQRamide (dns-PQRa), a putative NPFF antagonist, on conditioned place preference (CPP), in addition, its interaction with the opioid system. Two CPP experiments were conducted. First, rats were treated with dns-PQRa (4-13 mg/kg, i.p.) and paired with the non-preferred compartment while the vehicle was paired with the preferred compartment. Second, similar to experiment 1 except naloxone (1 mg/kg, i.p.) was given 10 min prior to each dns-PQRa administration. The post-drug place preference was examined after 4 alternative pairings. Another group of animals after repetitive dns-PQRa treatments were analyzed for levels of neurotransmitters in discrete brain areas. Dns-PQRa (4-13 mg/kg, i.p.) induced a significant dose-dependent CPP. The dns-PQRa-induced CPP was completely blocked by pretreatment with 1 mg/kg i.p. naloxone, while naloxone alone did not induce any place aversion. The chronic dns-PQRa-treated (13 mg/kg, i.p., b.i.d.) rats caused a significant increase in 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the olfactory tubercle compared to the vehicle-treated controls. There was also an increase in the turnover of serotonin in the olfactory tubercle, nucleus accumbens and medial prefrontal cortex. These results suggest that blockade of the NPFF system produces rewarding, possibly via an inhibition of the anti-opioid action of NPFF. These results also reveal a close relationship between NPFF, drug rewarding and the dopaminergic and serotoninergic neurons in the mesolimbic system.
 ...
PMID:Dansyl-PQRamide, a possible neuropeptide FF receptor antagonist, induces conditioned place preference. 1183 98

Neuropeptide FF (NPFF) and its analog 1DMe ([D-Tyr(1),(NMe)Phe(3)]NPFF) have been shown to reverse or potentiate morphine analgesia in rat depending on the supraspinal or spinal site of injection. The properties, in the mouse tail-flick test, of 1DMe and its related compound Nic-1DMe (Nicotinoyl-Pro-1DMe) were investigated after their local (i.c.v. and i.t.) and systemic administration. Whereas Nic-1DMe and 1DMe exhibit the same affinity and selectivity towards NPFF(1) and NPFF(2) receptors, Nic-1DMe, in contrast to 1DMe, is unable to inhibit morphine-induced analgesia after i.c.v. and i.p. administration. Conversely, after i.t. and i.p. administration, both neuropeptide FF analogs could potentiate morphine analgesia. Differences in disposition parameters between 1DMe and Nic-1DMe are evidenced, suggesting that the two neuropeptide FF analogs could stimulate differentially supraspinal neuropeptide FF receptors. The predominant activation of spinal neuronal pathways by Nic-1DMe could explain the selective pro-opioid action of this compound after i.t., i.c.v. and i.p. administration.
 ...
PMID:Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs. 1216 11

Neuropeptide FF, one of the mammalian PQRFamides, has been reported to affect the latency of the tail-flick response in rat. We intended to examine the nociceptive effect by the peptide PQRFamides from the comparative aspect. Using the dot immunoblot method with antiserum to FMRFamide as an assay system, a peptide (frog's nociception-related peptide, fNRP) which has the C-terminal sequence PQRFamide was isolated from the brain of the frog, Rana catesbeiana. The determined sequence, SIPNLPQRF-NH(2), is the same as that named first (frog growth hormone-releasing peptide-gene-related peptide-1: fGRP-RP-1, which is encoded in the cDNA of the fGRP precursor. Since the peptide was isolated from the frog brain, we tested another amphibian, the newt, which has a tail, by the hot beam tail-flick test. Intraperitoneal injection of fNRP significantly increased the latency of the pain response (tail-flick) 90 min after administration. The effect was blocked by simultaneous administration of 5 mM naloxone. The result provides evidence for the interaction of fNRP and opioid steps in the analgesia pathways in the newt.
 ...
PMID:Identification of a novel frog RFamide and its effect on the latency of the tail-flick response of the newt. 1260 Jun 86

The pharmacological effects of Neuropeptide FF (NPFF) analogs exhibiting different selectivities towards Neuropeptide FF1 (NPFF1) and Neuropeptide FF2 (NPFF2) receptors were investigated after supraspinal administration in mice. Injected into the third ventricle, VPNLPQRF-NH2, which is selective for Neuropeptide FF1 receptor induced a hypothermia while EFWSLAAPQRF-NH2 and SPAFLFQPQRF-NH2 which are selective for Neuropeptide FF2 receptor, did not. Furthermore, EFWSLAAPQRF-NH2 significantly increased the body temperature when compared to saline treated mice, indicating that Neuropeptide FF1 receptor could be responsible for hypothermia while Neuropeptide FF2 mediated an hyperthermic effect. After administration into the lateral ventricle, 1DMe ([D.Tyr1,(N.Me)Phe3]NPFF), a weakly selective Neuropeptide FF2 receptor agonist, exerted a clear anti-opioid effect in the tail flick test. The selective Neuropeptide FF1 receptor agonist VPNLPQRF-NH2 did not induce significant anti-opioid actions but rather increased, dose-dependently, morphine analgesia while EFWSLAAPQRF-NH2, the highest selective Neuropeptide FF2 receptor analog, induced the same pharmacological effect as VPNLPQRF-NH2 at comparable doses. These features indicate that the pro- and anti-opioid actions are not strictly related to the selectivity towards Neuropeptide FF2 or Neuropeptide FF1 receptor. Our data demonstrate that Neuropeptide FF1 and Neuropeptide FF2 receptors differently modulate nervous system functions.
 ...
PMID:Comparison of pharmacological activities of Neuropeptide FF1 and Neuropeptide FF2 receptor agonists. 1568 Feb 60

Neuropeptide FF (NPFF) has been characterized as an endogenous anti-opioid peptide because its intraventricular injection (icv) reversed morphine- and stress-induced analgesia, and precipitates withdrawal syndrome in morphine-dependent rats. The role of NPFF in other aspects of drug dependence is unknown. Therefore, the aim of this study was to determine NPFF influence on the expression of sensitization to the morphine-induced hyperlocomotion. As the opioid system plays a role in ethanol effects, the influence of NPFF on the expression of sensitization to hyperlocomotor effect of ethanol was also investigated. Our study indicated that acute administration of NPFF (5, 10, 20nmol, icv) inhibited the expression of morphine-induced sensitization at doses of 10 (P<0.05) and 20nmol (P<0.01), and also inhibited ethanol-induced sensitization at a dose of 20nmol (P<0.01). Furthermore, NPFF inhibited the acute locomotor effect of morphine (10 and 20nmol) but not that of ethanol. NPFF, given alone, did not change the locomotor activity of mice and did not disturb motor coordination of animals in the rotarod test. In conclusion, our experiments indicated that NPFF attenuated the acute morphine locomotion and the expression of sensitization to locomotion. We anticipate that NPFF may be involved in both of these effects.
 ...
PMID:The role of neuropeptide FF (NPFF) in the expression of sensitization to hyperlocomotor effect of morphine and ethanol. 1710 11

The tetra-peptide FMRF-NH(2) is a cardioexcitatory peptide in the clam. Using the antibody against this peptide, FMRF-NH(2)-like immunoreactive material was detected in mammalian CNS. Subsequently, mammalian FMRF-NH(2) immunoreactive peptides were isolated from bovine brain and characterized to be FLFQPQRF-NH(2) (NPFF) and AGEGLSSPFWSLAAPQRF-NH(2) (NPAF). The genes encoding NPFF precursor proteins and NPFF receptors 1 and 2 are expressed in all vertebrate species examined to date and are highly conserved. Among many biological roles suggested for the NPFF system, the possible modulatory role of NPFF in nocicetion and opiate analgesia has been most widely investigated. Pharmacologically, NPFF-related peptides were found to exhibit analgesia and also potentiate the analgesic activity of opiates when administered intrathecally but attenuate the opiate induced analgesia when administered intracerebroventricularly. RF-NH(2) peptides including NPFF-related peptides were found to delay the rate of acid sensing ion channels (ASIC) desensitization resulting in enhancing acid gated currents, raising the possibility that NPFF also may have a pain modulatory role through ASIC. The genes for NPFF as well as NPFF-R2, preferred receptor for NPFF, are highly unevenly expressed in the rat CNS with the highest levels localized to the superficial layers of the dorsal spinal cord. These two genes are also present in the dorsal root ganglia (DRG), though at low levels in normal rats. NPFF and NPFF-R2 mRNAs were found to be coordinately up-regulated in spinal cord and DRG of rats with peripheral inflammation. In addition, NPFF-R2 immunoreactivity in the primary afferents was increased by peripheral inflammation. The findings from the early studies on the analgesic and morphine modulating activities suggested a role for NPFF in pain modulation and this possibility is further supported by the distribution of NPFF and its receptor and the regulation of the NPFF system in vivo.
 ...
PMID:Modulatory role of neuropeptide FF system in nociception and opiate analgesia. 1785 90

Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFF A and pro-NPFF B) and two receptors (NPFF1 and NPFF2). Very recently, the novel compound RF9 was reported as the truly selective antagonist on NPFF receptors. The present study examined the effects of RF9 on the hypothermia and anti-morphine action induced by NPFF in mice. (1) RF9 injected into the third ventricle was devoid of any residual agonist activity, but it completely antagonized the hypothermic effects of NPFF (30 or 45 nmol) after cerebral administration in mice; (2) RF9 did not alter the tail-flick latency and morphine analgesia in nociceptive test, however, co-administration of RF9 prevented the anti-morphine action of intracerebroventricularly applied NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay. Collectively, our data indicate that RF9, behaving as a truly pure NPFF receptors antagonist, prevents NPFF-induced drops of the body temperature and morphine analgesia in mice. In addition, it further confirms that the hypothermia and anti-morphine action of NPFF are mediated directly by NPFF receptors.
 ...
PMID:Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist. 1827 24

Neuropeptide FF (NPFF) is a neurotransmitter known to modulate opioid-induced analgesia, sensitization, and reward. The expression of the immediate early gene c-Fos was analyzed to map the distribution of neurons whose activity is regulated by central administration of the NPFF(2)-selective agonist dNPA in naive mice and in animals who had received a systemic injection of morphine. The number of c-Fos positive nuclei was quantified in 28 brain regions. Intracerebro-ventricular injection of 1 nmol dNPA alone produced an overall inhibition of basal c-Fos expression in the brain with a statistically significant decrease in the lateral ventral part of the bed nucleus of the stria terminalis, the medial preoptic area, and the medial parvicellular part of the paraventricular nucleus of the hypothalamus. In contrast, intraperitoneal injection of morphine 5 mg.kg(-1) induced a statistically significant increase in c-Fos expression in the prelimbic cortex, the nucleus accumbens core and shell, the ventral pallidum, the lateral hypothalamus, and the nucleus of the tractus solitarius. dNPA counteracted morphine effect only in the nucleus accumbens shell and the ventral pallidum. The inhibitory effects of a low dose of dNPA in the hypothalamus and its afferents suggest that NPFF(2) receptors negatively regulate the hypothalamic-pituitary-adrenal axis in mouse. Moreover, our study identified the nucleus accumbens shell and ventral pallidum as putative sites of interaction between NPFF and opioid systems in relation with the modulation of acute morphine rewarding and locomotor effects.
 ...
PMID:Modulation of basal and morphine-induced neuronal activity by a NPFF(2) selective agonist measured by c-Fos mapping of the mouse brain. 2033 29

Neuropeptide FF (NPFF) belongs to an opioid-modulating peptide family. NPFF has been reported to play important roles in the control of pain and analgesia through interactions with the opioid system. However, very few studies examined the effect of supraspinal NPFF system on analgesia induced by opiates administered at the peripheral level. In the present study, intracerebroventricular (i.c.v.) injection of NPFF (1, 3 and 10 nmol) dose-dependently inhibited systemic morphine (0.12 mg, i.p.) analgesia in the mouse tail flick test. Similarly, i.c.v. administration of dNPA and NPVF, two agonists highly selective for NPFF(2) and NPFF(1) receptors, respectively, decreased analgesia induced by i.p. morphine in mice. Furthermore, these anti-opioid activities of NPFF and related peptides were blocked by pretreatment with the NPFF receptors selective antagonist RF9 (10 nmol, i.c.v.). These results demonstrate that activation of central NPFF(1) and NPFF(2) receptors has the similar anti-opioid actions on the antinociceptive effect of systemic morphine.
 ...
PMID:Central administration of neuropeptide FF and related peptides attenuate systemic morphine analgesia in mice. 2112 89


<< Previous 1 2 3 Next >>