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)

We investigated a possible link between galanin expression and evoked pain accompanying painful partial sciatic nerve lesions. Increased galanin immunoreactivity (IR) in the dorsal horn, in gracile nucleus, and in sensory neurons following chronic constriction injury (CCI) compared to complete sciatic transection suggested a facilitatory role in thermal and mechanical hypersensitivity (allodynia). We therefore investigated the effects of endogenous interleukin-6 (IL-6) and nerve growth factor (NGF) on allodynia and neuropeptide expression. IL-6 knockout mice showed decreased allodynia and galanin-IR compared to wild-type mice, but also decreased substance P (SP)-IR in the dorsal horn. Anti-NGF-treated rats with CCI also showed decreased allodynia and SP-IR, but increased galanin-IR in the dorsal horn. These results suggest that evoked pain is more tightly linked to SP than to galanin expression. If galanin's effects are inhibitory as the bulk of the literature suggests, its effects are subordinate to those of SP and to other changes following CCI.
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PMID:Galanin expression in neuropathic pain: friend or foe? 992 85

Galanin can normally be detected only in a few dorsal root ganglion (DRG) neurons, but it is dramatically upregulated after peripheral nerve injury in both rat and monkey. Galanin is stored in large dense core vesicles, which after axotomy are often found close to the membrane of afferent nerve endings in the dorsal horn. In the monkey there is an increase in galanin in many nerve terminals in the superficial dorsal horn after axotomy, but such an increase is more difficult to detect in the rat. Galanin is also present in local dorsal horn neurons, where it is upregulated by peripheral inflammation. Both galanin-R1 and galanin-R2 receptor mRNAs are expressed in rat DRGs, mainly in, respectively, large and small DRG neurons. Galanin-R1 receptor mRNA is downregulated in DRG neurons after axotomy, and a small decrease in galanin-R2 receptor mRNA levels can also be seen. After peripheral tissue inflammation galanin-R1 receptor mRNA levels decrease and galanin-R2 receptor mRNA levels increase. The present results show that galanin and galanin receptors are present in sensory and local dorsal horn neurons and are regulated by nerve injury and inflammation. Galanin may therefore be involved in processing of pain information, primarily exerting analgesic effects. Whereas local dorsal horn neurons represent a defense system against inflammatory pain, we have proposed that a second defense system, against neuropathic pain, is intrinsic to DRG neurons.
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PMID:Regulation of expression of galanin and galanin receptors in dorsal root ganglia and spinal cord after axotomy and inflammation. 992 86

We have previously suggested that the neuropeptides galanin and galanin message-associated peptide (GMAP) may have an inhibitory role in spinal nociception. The present study examined the effects of intrathecal (i.t.) administration of these two peptides on allodynia-like behaviours in response to mechanical and cold stimulation in rats after photochemically induced ischaemic peripheral nerve injury. I.t. galanin significantly alleviated the mechanical- and cold-allodynia-like behaviours in nerve injured rats, and was not associated with motor impairment or sedation. I.t. GMAP relieved mechanical allodynia much less than galanin. I.t. M-35, a high-affinity galanin receptor antagonist, did not significantly alter the response of the rats to mechanical or cold stimulation. At 1 or 2 weeks postinjury, around 15% of dorsal root ganglion (DRG) neuron profiles showed galanin-like immunoreactivity. These profiles were mostly small sized. Although the number of galanin positive cells was thus increased in the DRG in the present model, the increase was substantially less than after complete sciatic nerve section, as previously shown. The present results showed that spinal administration of galanin inhibited some abnormal pain-like behaviours in rats after partial peripheral nerve injury. These results further support an inhibitory function for galanin in nociception. However, endogenous galanin may not play a significant role in suppressing nociceptive input after partial ischaemic peripheral nerve injury, as the upregulation of galanin is moderate.
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PMID:Intrathecal galanin alleviates allodynia-like behaviour in rats after partial peripheral nerve injury. 1005 43

Partial sciatic nerve ligation (PSNL) is a widely used model for the study of neuropathic pain. However, there is little information on neuropeptide expression in primary sensory neurons after PSNL. We examined galanin (GAL) mRNA expression in L4 and L5 dorsal root ganglion (DRG) neurons of adult rats after PSNL. We found that 4 and 14 days after PSNL the percentages of GAL mRNA positive neurons were significantly increased in the ipsilateral DRG compared to the contralateral side. Using combined retrograde fluorescent dye tracing and in situ hybridization, we found that 47% of the injured neurons and 10% of the spared neurons were GAL mRNA positive. Since only 2-3% of neurons in the contralateral uninjured DRG were GAL mRNA positive, PSNL induced up-regulation of GAL mRNA in both injured and spared DRG neurons.
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PMID:Increase of galanin mRNA in lumbar dorsal root ganglion neurons of adult rats after partial sciatic nerve ligation. 1021 89

The possible physiological and pathophysiological role of monoamines-adrenergic transmitter (norepinephrine), serotonin; cholinergic transmitter (acetylcholine); inhibitory (gamma-aminobutyric acid) and excitatory (glutamate) amino acids; opioid and nonopioid peptides, enkephalins, beta-endorphin and substance P, neurokinin-A, neurokinin-B, neurotensin, cytokines, calcitonine gene-related peptide, galanin, neuropeptide Y, nerve growth factor, cholecystokinin; purines; nitric oxide; vanilloid receptor agonists (capasaicin); and nociceptin-in spinal transmission of pain is reviewed. The role of substance P, neurokinin-A and neurokinin-B in the dorsal horn has been identified. These were suggested to be primary afferent transmitters mediating or facilitating the expression of nociceptive inputs. Pronociceptive modulators will be discussed later. Recent findings showing that N-methyl-D-aspartate (NMDA) receptor activation generates nitric oxide and prostanoids that enhance pain transmission whereas adenosine release acts to control these NMDA-mediated events are also mentioned. The clinical importance of centrally acting alpha2-adrenoceptor agonists (clonidine and dexmedetomidine) is also discussed. Antinociceptive and morphine-potentiating drugs are ideal adjuvants for anesthesia; their application in spinal anesthesia is highlighted. The recent development in understanding the importance of noradrenergic transmission and subtypes of alpha2-adrenoceptors (alpha2A and alpha2B) for the first time is reviewed.
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PMID:Transmitters involved in antinociception in the spinal cord. 1023 Jul 4

After transection of the sciatic nerve there is a dramatic increase in both galanin/galanin message-associated peptide-like immunoreactivities and preprogalanin messenger RNA levels in rat and mouse lumbar 4 and 5 dorsal root ganglion neurons. There is strong evidence that after nerve injury leukemia inhibitor factor is a key molecule in the control of peptide expression both in sympathetic neurons and in dorsal root ganglion neurons, although the cells of origin of endogenous leukemia inhibitory factor remain to be established. We have therefore studied the effect of leukemia inhibitory factor on galanin expression in 72 h cultured dorsal root ganglion neurons from normal mice, leukemia inhibitory factor-deficient and heterozygous mice with immunohistochemistry and in situ hybridization. In cultures of leukemia inhibitory factor-deficient (-/-) mice only 13% of the dorsal root ganglion neurons expressed galanin message-associated peptide and in cultures from heterozygous (+/-) and wild-type (+/+) mice the corresponding figures were, respectively, 24 and 40%. After addition of leukemia inhibitory factor (10 or 50 ng/ml) to the culture medium, the number of neurons expressing galanin message-associated peptide was increased (up to 41%) in cultures from (-/-) animals after the high concentration and reached similar values in cultures from heterozygous animals incubated with the low concentration. These findings were supported by parallel analysis of prepro-galanin messenger RNA levels, where similar transcript levels and effects in the various cultures were observed in the non-radioactive in situ hybridization experiments. These results support the hypothesis that leukemia inhibitory factor is an important regulator of galanin/galanin message-associated peptide expression following axotomy, and may therefore be involved in the defence mechanisms against neuropathic pain at the level of dorsal root ganglion neurons.
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PMID:Leukemia inhibitory factor regulates galanin/galanin message-associated peptide expression in cultured mouse dorsal root ganglia; with a note on in situ hybridization methodology. 1036

Partial nerve injury is a potential cause of distressing chronic pain for which conventional analgesic treatment with opiates or anti-inflammatory agents is not very effective. Constriction nerve injury, widely used to study neuropathic pain, was shown here to induce interleukin-6 (IL-6) mRNA in a subset of rat primary sensory neurons. When we inflicted chronic nerve constriction on mice with null mutation of the IL-6 gene, the hypersensitivity to cutaneous heat and pressure that is induced in wild-type mice was not evident, the loss of substance P in sensory neurons was excessive and the induction of galanin in central sensory projections was reduced. In additional experiments, intrathecal infusion of IL-6 in rats was shown to stimulate synthesis of galanin in approximately one-third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL-6 mediates some of the hypersensitive responses that characterize peripheral neuropathic pain, and influences two neuropeptides that have been implicated in pain transmission.
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PMID:Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. 1038 13

In the present brief overview we summarize results from several studies focusing on two neuropeptides, galanin and neuropeptide Y (NPY) in discrete neuronal systems, where they coexist with classic transmitters. On the basis of studies in different animal models we propose that these peptides may be involved in regulation of certain CNS functions and that drugs acting on their receptors may be of use in new therapeutic strategies. At the spinal level galanin and NPY are regulated in DRG neurons by nerve injury and in dorsal horn neurons by inflammation. It is possible that this leads to attenuation of pain sensitivity. Moreover, both peptides may exert trophic effects, for example to enhance regeneration. In the hypothalamic arcuate nucleus NPY and its receptors are part of the feeding circuitry, and we suggest that derangement of these NPY neurons may at least in part underlay the lethal phenotype of anorectic mice, which die 22 days postnatally after showing decreased food intake and growth retardation. Expression of NPY and NPY receptors is changed in the hippocampus of mice comparatively early after prion inoculation, indicating that this peptide system is affected in this spongiform degenerative disease in a region of importance for learning and memory. Finally, galanin is co-localized with classic monoamine transmitters in two central systems, the dorsal raphe serotonin neurons and the locus coeruleus noradrenergic neurons. In both cases galanin causes hyperpolarization (at high concentrations) and prolongs monoamine-induced outward currents (at low concentrations), thus modulating activity in two systems of importance for many brain functions including mood regulation. It may therefore be interesting to analyse to what extent drugs affecting galaninergic transmission also may be efficient in the treatment of, for example, depression.
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PMID:Galanin and NPY, two peptides with multiple putative roles in the nervous system. 1042 30

Neuropeptide plasticity in the gracile nucleus is thought to play a role in the development of neuropathic pain following nerve injury. Two weeks after chronic constriction injury of adult rat sciatic nerve, galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities were increased in fibers and cells in the gracile nucleus ipsilateral to injury. At the electron microscopic level, this increased neuropeptide immunoreactivity was localized in myelinated axons, boutons, dendrites, neurons and glial cells. Galanin-, neuropeptide Y- and calcitonin gene-related peptide-immunoreactive boutons were frequently presynaptic to dendrites of both immunoreactive and non-immunoreactive neurons. However, no neuropeptide Y, galanin and calcitonin gene-related peptide messenger RNA was detected in the injured side gracile nuclei by in situ hybridization. These results show that partial nerve injury to the sciatic nerve induces increases in the content of galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities in synaptic terminals within the gracile nucleus, which suggests that there may be increased release of these neuropeptides following sensory or spontaneous stimulation of large-diameter primary afferents following partial nerve injury, perhaps one mechanism involved in neuropathic pain. We also show an apparent transfer of these neuropeptides to the cells of the gracile nucleus, both neurons and glial cells, an intriguing phenomenon of unknown functional significance.
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PMID:Ultrastructural localization of increased neuropeptide immunoreactivity in the axons and cells of the gracile nucleus following chronic constriction injury of the sciatic nerve. 1043 Apr 97

The development of a strain of galanin knockout mice has provided confirmation of a neuroendocrine role for galanin, as well as supporting results of previous physiological investigations indicating a role for galanin in analgesia and neuropathic pain, and potentially in neuronal growth and regeneration processes. Whether elevation of galanin expression in neurodegenerative disorders such as Alzheimer's disease represents a survival response or exacerbates functional deficit in afflicted individuals remains to be determined. More detailed analysis of the phenotype of the galanin knockout mouse should provide insights into the physiological role of galanin in memory and learning processes, as well as in hypothalamic function and other aspects of neuroendocrine regulation. Biochemical and molecular cloning efforts have demonstrated that the multiplicity of actions of galanin is matched by complexity in the distribution and regulation of galanin and its receptors. A focus on characterisation of galanin receptors has resulted in the molecular cloning of three receptor subtypes to date. The distribution and functional properties of these receptors have not yet been fully elucidated, currently precluding assignment of discrete functions of galanin to any one receptor subtype. It is not currently possible to reconcile available pharmacological data using analogs of galanin and chimeric peptides in functional assay systems with the pharmacological properties of cloned receptor subtypes. This highlights the value of further knockout approaches targeting galanin receptor subtypes, but also raises the possibility of the existence of additional receptor subtypes that have yet to be cloned, or that receptor activity may be modulated by regulatory molecules that remain to be identified. The development of receptor subtype-specific compounds remains a high priority to advance work in this area. The ability to selectively modulate the many different actions of galanin, through a clearer understanding of receptor structure-function relationships and neuronal distribution, promises to provide important insights into the molecular and cellular basis of galanin action in normal physiology, and may provide lead compounds with therapeutic application in the prevention and treatment of a range of disorders.
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PMID:Galanin and galanin receptors. 1045 68


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