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

In the arcuate nucleus of hypothalamus (ARC), galaninergic fibers form synaptic contacts with proopiomelanocortin neurons, which are involved in pain modulation. The present study assessed the role of exogenous and endogenous galanin in the modulation of nociception in the ARC of rats. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation was assessed by the hot-plate test and the Randall Selitto Test. Intra-ARC injection of galanin dose-dependently increased the HWLs in intact rats, indicating an antinociceptive role of exogenous galanin in the ARC. The antinociceptive effect of galanin was blocked by following intra-ARC injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, intra-ARC injection of galanin increased the HWL in rats with inflammation. Intra-ARC administration of galantide alone reduced the HWLs in rats with inflammation, while there were no influences of galantide on the HWL in intact rats. Taken together, the results show that galanin has an antinociceptive role in the ARC of intact rats and rats with inflammation.
Pain 2003 Nov
PMID:An antinociceptive role of galanin in the arcuate nucleus of hypothalamus in intact rats and rats with inflammation. 1458 Nov 21

We have examined the effect of systemically administered galnon, a novel low-molecular weight agonist of galanin receptors, on neuropathic pain-like behaviors in rats after photochemically induced partial nerve injury. Galnon is a galanin receptor ligand with moderate affinity to spinal cord membranes (K(D) of 6+/-0.6 microM). While intraperitoneally applied galnon produced no significant effect on mechanical or cold hypersensitivity, it dose-dependently prolonged heat withdrawal latency in nerve-injured rats. The effect of galnon was more potent on the injured side which has significantly shorter latency than the contralateral side. The anti-hyperalgesic effect of galanon was prevented by intrathecal M35, a galanin receptor antagonist. No side effects, such as sedation or motor impairment, were seen following systemic galnon treatment at the doses used. It is concluded that systemic galnon alleviated heat-hyperalgesic response in rats with partial sciatic nerve injury. This effect was likely to be mediated by activation of spinal galanin receptors.
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PMID:Systemic galnon, a low-molecular weight galanin receptor agonist, reduces heat hyperalgesia in rats with nerve injury. 1466 14

Although the tuberomammillary nucleus (TM) is well defined in terms of anatomy and neurochemistry, little is known about its function in nociceptive modulation. There was an abundance of galanin-immunoreactive fibers in the TM, and galanin has been implicated in pain processing. The present study assessed the role of galanin in the modulation of nociception in the TM of rats. Intra-TM injection of galanin dose-dependently increased the hindpaw withdrawal latency of rats to a noxious thermal stimulus, indicating an antinociceptive role of galanin in the TM. The antinociceptive effect of galanin was blocked by a subsequent intra-TM injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, there was abundant galanin receptor 1 (GalR1) in the TM, and the number of GalR1-positive neurons in the ipsilateral TM increased significantly after unilateral loose ligation of the sciatic nerve compared with the contralateral TM or the TM of intact rats. However, the number of GalR1-positive neurons was not significantly altered by carrageenan-induced inflammation, in either the ipsilateral or the contralateral TM. The results suggest that galanin and GalR1 in the TM may play important roles in pain regulation.
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PMID:Antinociceptive effects of galanin in the rat tuberomammillary nucleus and the plasticity of galanin receptor 1 during hyperalgesia. 1535 18

The fact that galanin, beta-endorphin and their receptors are present in the arcuate nucleus of hypothalamus (ARC), coupled with our previous observation that both beta-endorphin and galanin play antinociceptive roles in pain modulation in the ARC, made it of interest to study their interactions. The hindpaw withdrawal latency (HWL) in response to noxious thermal and mechanical stimulation was assessed by the hot-plate test and the Randall Selitto Test. We showed that the antinociceptive effect induced by intra-ARC injection of galanin was dose-dependently attenuated by the following intra-ARC injection of naloxone. Furthermore, intra-ARC administration of the selective mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) attenuated the increased HWL induced by intra-ARC injection of galanin in a dose-dependent manner, while the delta-opioid receptor antagonist naltrindole or the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) did not. Moreover, intra-ARC injection of a galanin receptor antagonist galantide attenuated intraperitoneal morphine-induced increases in HWLs. These results demonstrate that the antinociceptive effect of galanin was related to the opioid system, especially mu-opioid receptor was involved in, and that systemic morphine induced antinociception involves galanin in the ARC.
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PMID:Interactions of galanin and opioids in nociceptive modulation in the arcuate nucleus of hypothalamus in rats. 1554 39

Galanin, acting at the GalR1-3 subtypes of galanin receptors, is involved in the regulation of cognition, mood, feeding, seizure activity and pain. The understanding of galanin's effects in molecular and cellular terms has been hampered by the lack of receptor subtype selective ligands and antibodies. Previous in situ hybridization data showed that GalR1 and GalR2 receptors are abundant in the rat brain, while the distribution of GalR3 is contradictory and most studies demonstrated a low expression levels in the rat brain. The distribution of galanin receptor subtypes at protein level is unknown. In the present study, we report the regional distribution of the galanin receptors: GalR1 and non-GalR1 receptors, using a recently synthesized high affinity GalR2/3 selective ligand, galanin (2-11), and galanin (1-29), as competitors, in saturating (125)I-galanin membrane binding assay. We show that paraventricular nucleus (PVN) express predominantly GalR1, whereas areas like the dorsal raphe nucleus (DRN), hippocampus and amygdala express both the GalR1 and non-GalR1 receptors. We speculate that the GalR2/3 binding sites detected by galanin (2-11) binding in our study probably represent mostly GalR2 receptors. In addition, we show regionally specific and subtype specific regulation of galanin receptors. Status epilepticus (SE), known to deplete galanin from axonal projections of locus coeruleus and septum/diagonal band neurons in the hippocampus and to induce galanin expression in a subset of hippocampal cells, down regulates GalR2 receptor mRNA and proteins by 30% without altering the GalR1 receptors.
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PMID:Distribution and differential regulation of galanin receptor subtypes in rat brain: effects of seizure activity. 1594 3

Numerous reports suggest a significant role of peripheral galanin (GAL) in pain transmission; however, due to the lack of selective galanin receptor agonists and antagonists, the role of GAL receptors (GalR1-3) in pain transmission remains unclear. In this study, a new agonist, M617, that preferentially binds to GalR1, a GalR2 agonist (AR-M1896), and a GalR2 antagonist (M871) were tested in the periphery to elucidate the role of peripheral GalR1 and GalR2 in nociception. Ipsilateral, but not contralateral, hindpaw injection of M617 reduced capsaicin (CAP)-induced flinching by approximately 50%, suggesting that GalR1 activation produces anti-nociception. This anti-nociceptive effect was blocked by intraplantar injection of the non-selective GalR antagonist M35. In contrast ipsilateral, but not contralateral, intraplantar injection of GalR2 agonist AR-M1896 enhanced the CAP-induced nociception (1.7-fold). The GalR2 antagonist M871 blocked the pro-nociceptive effect of AR-M1896 in a dose-dependent manner. This antagonist had no effect on nociceptive behaviors induced by CAP alone. The data demonstrate that activation of peripheral GalR1 results in anti-nociception but activation of peripheral GalR2 produces pro-nociception. Thus, the use of these pharmacological tools may help to elucidate the contribution of GalR subtypes in nociceptive processing, identifying potential drug targets for the treatment of peripheral pain.
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PMID:Activation of peripheral galanin receptors: differential effects on nociception. 1699 22

The neuropeptide galanin and galanin receptors are widespread throughout cortical, limbic and midbrain areas implicated in reward, learning/memory, pain, drinking and feeding. While many studies have shown that galanin produces a variety of presynaptic and post-synaptic responses, work studying the effects of galanin on neural activation is limited. The present study examined patterns of c-Fos immunoreactivity resulting from intracerebroventricular administration of galanin versus saline injection in awake rats. An initial comprehensive qualitative survey was conducted to identify regions of high c-Fos expression followed up with quantitative analysis. Galanin induced a significant increase in c-Fos levels relative to saline-treated controls in dorsomedial hypothalamus and in the central nucleus of the amygdala. This pattern of activation was also produced by galanin receptor type 1 agonist M617. The present findings confirm that galanin upregulates c-Fos activation in hypothalamic nuclei, and supports roles for galanin in central amygdala-mediated regulation of stress-responses, food intake, and Pavlovian conditioning.
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PMID:Intracerebroventricular administration of galanin or galanin receptor subtype 1 agonist M617 induces c-Fos activation in central amygdala and dorsomedial hypothalamus. 1733 94

Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and micro-selective beta-funaltrexamine (beta-FNA). In contrast, a delta-opioid receptor antagonist, naltrindole (NTI) or the kappa-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL.
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PMID:Interactions of galanin with endomorphin-2, vasopressin and oxytocin in nociceptive modulation of the trigemino-hypoglossal reflex in rats. 1794 54

The neuropeptide galanin has been shown to play a role in psychiatric disorders as well as in other biological processes including regulation of pain threshold through interactions with three G-protein coupled receptors, galanin receptor subtypes 1-3 (GalR1-3). While most of the pharmacological studies on galanin in stress-related disorders have been done with rats, the continuous development of genetically engineered mice involving galanin or its receptor subtype(s) validates the importance of mouse pharmacological studies. The present study on mice examined the homeostatic, endocrinological and neuroanatomical effects of the galanin, injected intracerebroventricularly (i.c.v.), in regulation of stress responses after restraint stress. Furthermore, the roles of GalR1 on these effects were studied using GalR1 knockout (KO) mice. The core body temperature and the locomotor activity were monitored with radio telemetry devices. Galanin (i.c.v.) decreased locomotor activity and exerted a bidirectional effect on the restraint stress-induced hyperthermia; a high dose of galanin significantly attenuated the stress-induced hyperthermic response, while a low dose of galanin moderately enhanced this response. The bidirectional effect of galanin was correlated with changes in stress hormone levels (adrenocorticotropic hormone and corticosterone). To neuroanatomically localize the effects of galanin on stress response, cFos immunoreactivity was assessed in galanin receptor rich areas; paraventricular nucleus (PVN) of the hypothalamus and the locus coeruleus (LC), respectively. A high dose of galanin significantly induced cFos activity in the LC but not in the PVN. In GalR1KO mice, a high dose of galanin failed to induce any of the above effects, suggesting the pivotal role of GalR1 in decreased locomotor activity and stress-resistant effects caused by galanin i.c.v. injection studied here.
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PMID:Bidirectional regulation of stress responses by galanin in mice: involvement of galanin receptor subtype 1. 1927 14

Treatment of chronic neuropathic pain resulted from peripheral nerve injury is one of the most difficult problems in modern clinical practice. The use of cell lines as biologic "minipumps" to chronically deliver anti-nociceptive molecules into the pain-processing centers of spinal cord is a newly developing technique for the treatment of pain. Moreover, spinal administration of exogenous galanin (GAL) is a useful target for the treatment of chronic pain after nerve injury. Because of better histocompatibility, lower immunogenicity and reproducibility, immortalized astrocytes (IAST) have been served as a promising cellular vehicle to deliver therapeutic molecules into CNS. In this study, the rat IAST was transfected with rat preprogalanin cDNA and the galanin-synthesizing and secreting cell line, IAST/GAL, was isolated. After cells were transplanted into the subarachnoid space of rats with chronic neuropathic pain induced by spared nerve injury (SNI) of sciatic nerve, their analgesic potential was evaluated by behavioral tests. The results showed that IAST/GAL transfected with preprogalanin gene could express and secrete significantly higher level of GAL protein in vitro and in vivo as compared with control cells. In addition, the pain-related behaviors, thermal hyperalgesia and mechanical allodynia were significantly alleviated during the 1-7 weeks after grafts of IAST/GAL cells, which could be reversed by galanin receptor antagonist M35 temporarily. Taken together, these data suggest that subarachnoid transplant of immortalized galanin-overexpressing astrocytes near the pain-processing centers was able to reverse the development of chronic neuropathic pain, which offers an adjunct approach to currently used therapies for the pain management.
Eur J Pain 2010 Jul
PMID:Subarachnoid transplantation of immortalized galanin-overexpressing astrocytes attenuates chronic neuropathic pain. 2000 1


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