Abstract：
:The analgesic effect of alpha-2 adrenergic receptor (α2AR) agonists, which relieve chronic neuropathic pain, is highly variable among individuals. Here, we used a mouse model of spared nerve injury (SNI) to show that treatment time after the establishment of neuropathic pain was important for the variability in the analgesic efficacy of α2AR agonists, which was related to the activity of regulator of G-protein signaling protein 4 (RGS4). Intrathecal treatment with α2AR agonists, clonidine (0.1-1 nmol) or dexmedetomidine (0.3-1 nmol), relieved mechanical allodynia and thermal hyperalgesia on postoperative day (POD) 14, but their efficacy was weaker on POD28 and absent on POD56. The RGS4 level of plasma membrane was increased on POD56 compared to that on POD14. Moreover, in RGS4-deficient or RGS4 inhibitor (CCG50014)-treated mice, the analgesic effect of the α2AR agonists was conserved even on POD56. The increased plasma membrane RGS4 expression and the reduced level of active Gαi after clonidine injection on POD56 were completely restored by CCG50014. Higher doses of clonidine (10 nmol) and dexmedetomidine (3 nmol) relieved neuropathic pain on POD56 but were accompanied with serious side effects. Whereas, the coadministration of CCG50014 with clonidine (1 nmol) or dexmedetomidine (1 nmol) did not cause side effects. These findings demonstrated that SNI-induced increase in plasma membrane RGS4 expression was associated with low efficacy of α2AR agonists in a model of persistent, chronic neuropathic pain. Furthermore, α2AR agonist administration together with RGS4-targeted intervention represents a novel strategy for the treatment of neuropathic pain to overcome dose-limiting side effects.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Yoon SY,Roh DH,Yeo JH,Woo J,Han SH,Kim KSdoi
10.1016/j.neuroscience.2020.12.021subject
Has Abstractpub_date
2020-12-25 00:00:00pages
177-194eissn
0306-4522issn
1873-7544pii
S0306-4522(20)30798-3journal_volume
455pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract：:Activity within the mesolimbic dopamine system is associated with the performance of naturally motivated behaviors, one of which is aggression. In male rats, aggressive behavior induces neurochemical changes within the nucleus accumbens, a key structure within the mesolimbic dopamine system. Corresponding studies have...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2012.09.064
更新日期：2012-12-27 00:00:00
abstract：:Two radial maze tasks, random foraging and delayed spatial win-shift, have been used to investigate, in rats, the functions and inter-relationships of structures connected through the corticostriatal loops, such as the prelimbic cortex, nucleus accumbens, ventral pallidum and mediodorsal thalamus. The random foraging ...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(02)00108-2
更新日期：2002-01-01 00:00:00
abstract：:There is increasing evidence that a subset of midbrain dopamine (DA) neurons uses glutamate as a co-transmitter and expresses vesicular glutamate transporter (VGLUT) 2, one of the three vesicular glutamate transporters. In the present study, double in situ hybridization was used to examine tyrosine hydroxylase (TH) an...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2008.07.032
更新日期：2008-09-22 00:00:00
abstract：:Histochemical and immunohistochemical techniques were used to determine relationships between the parvalbumin or calbindin D28k content and the cytochrome oxidase or carbonic anhydrase activity of neurons in lumbar dorsal root ganglia in rat. Subpopulations of dorsal root ganglion neurons that displayed parvalbumin- o...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(89)90216-9
更新日期：1989-01-01 00:00:00
abstract：:Dorsal vagal complex (DVC) AMPK regulation of food intake in the estradiol-treated ovariectomized (OVX) female rat is energy state-dependent. Here, RT-PCR array technology was used to identify estradiol-sensitive AMPK-regulated DVC signal transduction pathways that exhibit differential reactivity to sensor activation ...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2014.10.068
更新日期：2015-01-22 00:00:00
abstract：:Microinjection of L-glutamate into a subregion of the gigantocellular nucleus of the rat medulla oblongata significantly lowers arterial pressure. This vasodepressor area, the gigantocellular depressor area, is topographically distinct from other vasoactive areas of the medulla. We sought to determine the efferent pro...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(94)90503-7
更新日期：1994-06-01 00:00:00
abstract：:Reversal learning is a domain that involves cognitive flexibility and is defined as the ability to rapidly alter established patterns of behavior when confronted with changing circumstances. This function depends critically on the orbitofrontal cortex (OFC) in the prefrontal cortical (PFC) structure, which is among th...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2010.08.037
更新日期：2010-11-10 00:00:00
abstract：:The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. I...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(89)90028-6
更新日期：1989-01-01 00:00:00
abstract：:Earlier studies have implicated brain-derived neurotrophic factor in stress and in the mechanism of action of antidepressants. It has been shown that antidepressants upregulate, whereas corticosterone downregulates, brain-derived neurotrophic factor expression in rat brain. Whether various classes of antidepressants r...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2005.12.058
更新日期：2006-01-01 00:00:00
abstract：:High-intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can prod...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2015.09.040
更新日期：2015-12-03 00:00:00
abstract：:The effects of systemically administered interleukin-1beta (1.0 microg), interleukin-6 (1.0 microg) and interleukin-2 (1.0 microg) on in vivo variations of monoamines were assessed in the nucleus accumbens. Administration of interleukin-1beta did not affect extracellular accumbal dopamine, provoked a modest rise of ho...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(98)00271-1
更新日期：1999-01-01 00:00:00
abstract：:In spite of the existence of pedunculopontine tegmental nucleus (PPTg) projections to cerebellar nuclei, their nature and functional role is unknown. These fibers may play a crucial role in postural control and may be involved in the beneficial effects induced by deep-brain stimulation (DBS) of brainstem structures in...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2015.12.055
更新日期：2016-03-11 00:00:00
abstract：:Skilled performance and acquisition is dependent upon afferent input to motor cortex. The present study used short-latency afferent inhibition (SAI) to probe how manipulation of sensory afference by attention affects different circuits projecting to pyramidal tract neurons in motor cortex. SAI was assessed in the firs...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2017.07.028
更新日期：2017-09-17 00:00:00
abstract：:The binding of the GABAA/benzodiazepine receptor agonist [3H]flunitrazepam was studied in the hippocampus of rats kindled by daily stimulation of the Schaffer collaterals, using semi-quantitative autoradiography. Two kindled stages were investigated: (i) 24 h after the last generalized tonic-clonic seizure (fully kind...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(95)00158-f
更新日期：1995-09-01 00:00:00
abstract：:In mammals, the extraocular muscle fibers can be categorized in singly-innervated and multiply-innervated muscle fibers. In the monkey oculomotor, trochlear and abducens nucleus the motoneurons of multiply-innervated muscle fibers lie separated from those innervating singly-innervated muscle fibers and show different ...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2005.10.038
更新日期：2006-02-01 00:00:00
abstract：:N-methyl-D-aspartate-receptors are implicated in several neuropathological conditions including epilepsy. As a model of complex partial seizures, rapid hippocampal kindling was chosen to investigate changes in the expression of messenger RNAs encoding the N-methyl-D-aspartate-receptor subunits NR1, NR2A and NR2B both ...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(93)90064-m
更新日期：1993-11-01 00:00:00
abstract：:Alzheimer's disease (AD) is characterized by the accumulation and deposition of plaques of amyloid-β (Aβ) peptide in the brain. Growing epidemiological and experimental studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts neuroprotection against AD. However, the underlying mechanisms of the action rem...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2016.01.041
更新日期：2016-05-13 00:00:00
abstract：:Using an indirect immunofluorescence method the distribution of vasoactive intestinal peptide (VIP) immunoreactivity was studied in human foetus and newborn infant spinal cord and dorsal root ganglia. Further, for comparison some newborn infant brains were also investigated. Vasoactive intestinal peptide-like immunore...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(85)90173-3
更新日期：1985-01-01 00:00:00
abstract：:Efferent projections of intrastriatally implanted striatal neurons have been studied using a combination of anterograde and retrograde axonal tracers. Adult rats subjected to a unilateral ibotenic acid lesion of the head of the caudate putamen received cell suspension grafts obtained from 14 15-day-old striatal primor...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(89)90256-x
更新日期：1989-01-01 00:00:00
abstract：:The effect of re-exposure of rats to an aversive environment on the induction of long-term potentiation was investigated in the CA3 region 3 and 12 h after contextual conditioning. Electro-physiological recordings showed that re-exposure of rats to the conditioning chamber produced a significant and long-lasting decre...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(97)00285-6
更新日期：1998-01-01 00:00:00
abstract：:Handedness in humans and paw preference (PP) in rodents have been associated with neural and physiological correlates, which frequently appear to be sex-specific. The present study examines sex differences in the effects of differential PP on post mortem measures of regional monoamine activity in adult Long-Evans rats...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2011.12.001
更新日期：2012-01-27 00:00:00
abstract：:Mutations in the presenilin 1 and 2 genes cause the majority of early onset familial forms of Alzheimer's disease. Here we describe the biochemical and immunohistochemical characterization of calsenilin, a novel calcium binding protein that we have previously shown to interact with presenilins 1 and 2, in mouse brain....
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(02)00251-8
更新日期：2002-01-01 00:00:00
abstract：:The dorsal hippocampus (DH) is a structure of the limbic system that is involved in emotional, learning and memory processes. There is evidence indicating that the DH modulates cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint stress (RS) is an unavoidable stress situation that ev...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2013.11.022
更新日期：2014-01-31 00:00:00
abstract：:Most mammals rely on semiochemicals, such as pheromones, to mediate their social interactions. Recent studies found that semiochemicals are perceived by at least two distinct chemosensory systems: the main and accessory olfactory systems, which share many molecular, cellular, and anatomical features. Nevertheless, the...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2011.05.039
更新日期：2011-08-25 00:00:00
abstract：:The Tg2576 mouse model of Alzheimer's disease (AD) exhibits age-dependent amyloid beta (Abeta) deposition in the brain. We studied electroencephalographically defined sleep and the circadian regulation of waking activities in Tg2576 mice to determine whether these animals exhibit sleep abnormalities akin to those in A...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2004.11.018
更新日期：2005-01-01 00:00:00
abstract：:GABAergic neurons occur in the myenteric plexus and submucosa and their innervations of the gut, where GABA stimulates motor neurons, and non-neural cells via "central type" GABA(A) receptors. These receptors occur on half of the neurons in the rat intestine. The GABA(A) receptor is a ligand-gated chloride channel con...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(99)00174-8
更新日期：1999-01-01 00:00:00
abstract：:The concentration of intracellular Ca(2+) ([Ca(2+)](i)) influences neuronal properties ranging from excitability to neurotransmitter release. Persistent inflammation is associated with changes in the properties of primary afferent neurons ranging from excitability to transmitter release. The purpose of the present stu...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2008.02.006
更新日期：2008-04-22 00:00:00
abstract：:Changes in the distribution of 5-hydroxytryptamine-like immunoreactivity have been examined in enteric neurons at various times after microsurgical lesions of the enteric plexuses. In the myenteric plexus, varicose immunoreactive nerve fibres disappeared or were reduced in number in ganglia anal to an interruption of ...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/0306-4522(82)90271-8
更新日期：1982-02-01 00:00:00
abstract：:Previous attempts to reproduce striatonigral degeneration, the core pathology underlying Parkinsonism in multiple system atrophy, have been impeded by interactions in the neurotoxins used to replicate striatal and nigral degeneration in rodents. To overcome these interactions, we have developed a new model of striaton...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/s0306-4522(02)00401-3
更新日期：2002-01-01 00:00:00
abstract：:The Ts65Dn mouse model of Down syndrome (DS) and Alzheimer's disease (AD) exhibits cognitive impairment and degeneration of basal forebrain cholinergic neurons (BFCNs). Our prior studies demonstrated that maternal choline supplementation (MCS) improves attention and spatial cognition in Ts65Dn offspring, normalizes hi...
journal_title：Neuroscience
pub_type： 杂志文章
doi：10.1016/j.neuroscience.2016.11.001
更新日期：2017-01-06 00:00:00
