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

Since the neuropeptide galanin's discovery in 1983, information has accumulated that implicates it in a wide range of functions, including pain sensation, stress responses, appetite regulation, and learning and memory. This article reviews the evidence for specific functions of galanin in cognitive processes. Consistencies as well as gaps in the literature are organized around basic questions of methodology and theory. This review shows that although regularities are evident in the observed behavioral effects of galanin across several methods for measuring learning and memory, generalization from these findings is tempered with concerns about confounds and a restricted range of testing conditions. Furthermore, it is revealed that many noncognitive behavioral constructs that are relevant for assessing potential roles for galanin in cognition have not been thoroughly examined. The review concludes by laying out how future theory and experimental work can overcome these concerns and confidently define the nature of the association of galanin with particular cognitive constructs.
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PMID:Galanin and cognition. 1581 8

Bone is the most common site of chronic pain in patients with metastatic cancer. What remains unclear are the mechanisms that generate this pain and why bone cancer pain can be so severe and refractory to treatment with opioids. Here we show that following injection and confinement of NCTC 2472 osteolytic tumor cells within the mouse femur, tumor cells sensitize and injure the unmyelinated and myelinated sensory fibers that innervate the marrow and mineralized bone. This tumor-induced injury of sensory nerve fibers is accompanied by an increase in ongoing and movement-evoked pain behaviors, an upregulation of activating transcription factor 3 (ATF3) and galanin by sensory neurons that innervate the tumor-bearing femur, upregulation of glial fibrillary acidic protein (GFAP) and hypertrophy of satellite cells surrounding sensory neuron cell bodies within the ipsilateral dorsal root ganglia (DRG), and macrophage infiltration of the DRG ipsilateral to the tumor-bearing femur. Similar neurochemical changes have been described following peripheral nerve injury and in other non-cancerous neuropathic pain states. Chronic treatment with gabapentin did not influence tumor growth, tumor-induced bone destruction or the tumor-induced neurochemical reorganization that occurs in sensory neurons or the spinal cord, but it did attenuate both ongoing and movement-evoked bone cancer-related pain behaviors. These results suggest that even when the tumor is confined within the bone, a component of bone cancer pain is due to tumor-induced injury to primary afferent nerve fibers that innervate the tumor-bearing bone. Tumor-derived, inflammatory, and neuropathic mechanisms may therefore be simultaneously driving this chronic pain state.
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PMID:Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain. 1581 67

In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes.
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PMID:Generation and phenotypic characterization of a galanin overexpressing mouse. 1589 31

The 29/30 amino acid neuropeptide galanin is present in a small population of DRG neurons under normal condition but is strongly upregulated after nerve injury. There is evidence that this upregulated galanin has trophic actions, for example promoting neurite outgrowth as well as influencing pain processing. In fact, both pro- and antinociceptive effects have been reported, probably relating to activation of different receptors. It has been proposed that presynaptic GalR2 receptors are pro-nociceptive by enhancing release of excitatory transmitters in the dorsal horn, and anti-nociceptive via an action on GalR1-positive interneurons. These neurons have recently been shown to be glutamatergic. Several other peptides and molecules are also regulated by nerve injury. Here we focus on neuropeptide tyrosine (NPY), which is upregulated in parallel with galanin. We review data reporting on coexistence between galanin and NPY and between these two peptides and the two NPY receptors Y1 and Y2. The data show considerable overlap, and it will be an important task to analyse how cross-talk between these neuropeptides can influence pain processing. It is proposed that such cross-talk can occur by release of peptides from DRGs neuron somata within dorsal root ganglia. To what extent these mechanisms shown to exist in rodents also occur in human is important, if one wants to discuss novel strategies for pain treatment on the basis of these findings. So far information is limited, but it has been demonstrated that galanin is expressed in DRGs and possibly also regulated.
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PMID:Galaninergic mechanisms at the spinal level: focus on histochemical phenotyping. 1589 17

The Third Galanin Symposium presented many different and exciting results on galanin research reflecting a major progress since the previous symposium in 1998. A major impression was the many possible relationships of galaninergic mechanisms to important brain functions such as development, cognition and ageing as well as many aspects related to a wide spectrum of diseases, including Alzheimer's disease, anxiety/depression, addiction, obesity, pain and tumour growth. These studies were based on an extensive armament of methodologies including various strains of transgenic mice. Unfortunately, the pharmaceutical industry had only a minor participation. Nevertheless, exciting developments in the generation of agonists and antagonists are emerging, providing hope that we at the next symposium will be able to validitate many of the challenging hypotheses concerning galanin and disease with the help of pharmacological tools.
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PMID:Galanin and its receptors: introduction to the Third International Symposium, San Diego, California, USA, 21-22 October 2004. 1590

Women are more than three times as likely as men to experience migraine headaches and temporomandibular joint pain, and painful episodes are often linked to the menstrual cycle. To understand how hormone levels may influence head and face pain, we assessed expression of pain-associated neuropeptides and estrogen receptor alpha (ERalpha) during the natural estrous cycle in mice. Gene expression was analyzed in the trigeminal ganglia of cycling female mice at proestrus, estrus and diestrus using RT-PCR. Peptide/protein expression in trigeminal neurons was analyzed using immunohistochemistry. ERalpha mRNA was present at all stages and highest at estrus. ERalpha protein was present in the cytoplasm of medium-sized and small trigeminal neurons. ERalpha immunoreactive neurons were most common at diestrus. CGRP and ANP mRNAs did not change across the estrous cycle, while expression of galanin and NPY mRNAs were strongly linked to the estrous cycle. Galanin mRNA levels peaked at proestrus, when expression was 8.7-fold higher than the diestrus levels. Galanin immunoreactivity also peaked at proestrus. At proestrus, 7.5% of trigeminal neurons contained galanin, while at estrus, 6.2% of trigeminal neurons contained galanin, and at diestrus, 4.9% of trigeminal neurons contained galanin. NPY mRNA peaked at estrus, when levels were 4.7-fold higher than at diestrus. Our findings suggest that estrogen receptors in trigeminal neurons modulate nociceptive responses through effects on galanin and NPY. Variations in neuropeptide content in trigeminal neurons across the natural estrous cycle may contribute to increases in painful episodes at particular phases of the menstrual cycle.
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PMID:Ovarian steroids regulate neuropeptides in the trigeminal ganglion. 1593 15

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

The neuropeptide galanin is present at high levels within the dorsal root ganglia (DRG) and spinal cord during development and after peripheral nerve damage in the adult. This pattern of expression suggests that it may play a role in the adaptive response of the peripheral nervous system (PNS) to injury. Several experimental paradigms have demonstrated that galanin modulates pain transmission, particularly after nerve injury. In our laboratory we have used a transgenic approach to further elucidate the functions of galanin within the somatosensory system. We have generated mice which over-express galanin (either inducibly after nerve injury, or constitutively), and knock-out (KO) mice, in which galanin is absent in all cells, throughout development and in the adult. Analysis of the nociceptive behaviour of the galanin over-expressing animals, before and after nerve injury, supports the view that galanin is an inhibitory neuromodulator of spinal cord transmission. In apparent contradiction to these findings, galanin KO animals fail to develop allodynia and hyperalgesia after nerve injury. However, further studies have shown that galanin is critical for the developmental survival of a subset of small diameter, unmyelinated sensory neurons that are likely to be nociceptors. This finding may well explain the lack of neuropathic pain-like behaviour after injury in the KO animals. Furthermore, the developmental survival role played by galanin is recapitulated in the adult where the peptide is required for optimal neuronal regeneration after injury, and in the hippocampus where it plays a neuroprotective role after excitotoxic injury.
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PMID:Use of genetically engineered transgenic mice to investigate the role of galanin in the peripheral nervous system after injury. 1594 11

Genetically modified mice with transgenic overexpression of galanin or depletion of genes for galanin or galanin receptors have become available, providing a new approach for analyzing the role of galanin in nociception. Mice overexpressing galanin had a moderate heat hypoalgesia, reduced spinal sensitization after repetitive C-fiber stimulation and reduced development of neuropathic pain-like behavior after sciatic nerve injury. On the other hand, mice lacking the GALR1 receptor (Galr1-/-) exhibited only slight increase in heat nociception in the hot plate, but not tail flick, test and showed no increase in spinal sensitization. The duration, but not magnitude, of neuropathic pain-like behaviors, was increased in Galr1-/- mice after nerve injury. These results support an inhibitory effect of galanin on nociception, but the physiological role played by galanin via GALR1 receptors needs to be further studied.
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PMID:Galanin and spinal nociceptive mechanisms: recent results from transgenic and knock-out models. 1594 13

The neuropeptide galanin has important effects on hormone secretion from the hypothalamus and pituitary, and it may also be involved in central biological processes such as pain, memory, and food intake. Yet, there is limited knowledge about how these processes are reflected by circulating galanin. To study the levels and molecular forms of galanin in the human circulation, plasma was analysed from 26 healthy subjects, 14 women and 12 men, using two extraction methods and a specific radioimmunoassay for human galanin. Galanin-LI levels in unextracted plasma were higher (141-191 pmol/L) than after immunoextraction (3.4-30.7 pmol/L) and Sep Pak extraction (2.2-12.6 pmol/L). Galanin immunoreactivity after Sep Pak and immunoextraction correlated (r = 0.74, p<0.001). Galanin-LI levels were significantly higher in the men than in the women (p = 0.01) after Sep Pak extraction. A small increase in galanin-LI was seen with age in the women (r = 0.54, p < 0.05). The proportion of Sep Pak extracted galanin-LI increased with age in the women (r = 0.73, p < 0.05)) but not in the men.
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PMID:Galanin in human plasma. 1594 32


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