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Yuqiu Zhang - One of the best experts on this subject based on the ideXlab platform.

  • evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of Monoarthritis
    Clinical and Experimental Pharmacology and Physiology, 2010
    Co-Authors: Weishi Zhang, Jia Le Yang, Xiaoming Deng, Yuqiu Zhang
    Abstract:

    Summary 1. Spinal glial cells play a key role in developing and maintaining allodynia and hyperalgesia following tissue inflammation. Dexmedetomidine, a highly selective α2-adrenoceptor (α2-AR) agonist, has exhibited a significant analgesic effect in various rodent models of chronic pain. However, whether spinal glial activation is involved in the analgesic effect of dexmedetomidine remains unknown. The present study investigated whether spinal administration of dexmedetomidine could antagonize glial activation in the spinal dorsal horn and attenuate thermal hyperalgesia in complete Freund’s adjuvant (CFA)-induced ankle joint monoarthritic (MA) rats. 2. Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Repeated lumbar puncture (LP) administration of dexmedetomidine (10 μg) significantly attenuated MA-induced thermal hyperalgesia in a cumulative manner. Monoarthritis-induced spinal glial activation was also suppressed following dexmedetomidine application. The α2A-AR, essential for the antinociceptive effects of α2-AR agonists, was detected in spinal neurons and glia, as well as in dorsal root ganglion primary afferent neurons, which may be implicated in dexmedetomidine-induced suppression of spinal glial activation and antihyperalgesic effects. 3. These data provide the first evidence that blocking spinal glial activation is involved in the analgesic action of dexmedetomidine.

  • dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of Monoarthritis
    Acta Pharmacologica Sinica, 2010
    Co-Authors: Weishi Zhang, Jia Le Yang, Xiaoming Deng, Yuqiu Zhang
    Abstract:

    To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (α2AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by Monoarthritis (MA). MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 μg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.

  • evidence for suppression of electroacupuncture on spinal glial activation and behavioral hypersensitivity in a rat model of Monoarthritis
    Brain Research Bulletin, 2008
    Co-Authors: S Sun, Zhiqi Zhao, Hongbin Cao, Mei Han, Yuqiu Zhang
    Abstract:

    Our previous study demonstrated that single intrathecal (i.t.) application of fluorocitrate, a glial metabolic inhibitor, synergized electroacupuncture (EA) antagonizing behavioral hypersensitivity in complete Freund's adjuvant (CFA)-induced monoarthritic rat. To further investigate the relationship between spinal glial activation and EA analgesia, the present study examined the effects of multiple EA on spinal glial activation evoked by Monoarthritis (MA). The results showed that (1) unilateral intra-articular injection of CFA produced a robust glial activation on the spinal cord, which was associated with the development and maintenance of behavioral hypersensitivity; (2) multiple EA stimulation of ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints or i.t. injection of fluorocitrate (1 nmol) significantly suppressed spinal glial activation; (3) inhibitory effects of EA on spinal glial activation and behavioral hypersensitivity were significantly enhanced when EA combined with fluorocitrate, indicating that disruption of glial function may potentiate EA analgesia in inflammatory pain states. These data suggested that analgesic effects of EA might be associated with its counter-regulation to spinal glial activation, and thereby provide a potential strategy for the treatment of arthritis.

  • alterations of membrane properties and effects of d serine on nmda induced current in rat anterior cingulate cortex neurons after Monoarthritis
    Neuroscience Letters, 2005
    Co-Authors: Jidong Guo, Hua Wang, Yuqiu Zhang, Zhiqi Zhao
    Abstract:

    Abstract Accumulated evidence implicates the anterior cingulate cortex (ACC) in pain processing. The activation of the NMDA receptor requires the occupation of both the glutamate site and the glycine site. d -Serine released by astrocytes is presumed to be an endogenous ligand for the glycine site of the NMDA receptor. Using whole-cell patch clamp recording, membrane characteristics and effects of exogenous d -serine on NMDA-evoked currents were examined in neurons in ACC slices from normal and complete Freund's adjuvant-induced monoarthritic rats. Neurons from rats with Monoarthritis exhibited more depolarized membrane potential, lower firing threshold, lower input resistance and higher slope conductance compared with normal rats. The NMDA-evoked currents were enhanced by d -serine (20 μM) in both normal (135.3 ± 4.3% of control, p p d -serine was greater in arthritic rats than control rats ( p

Thomas R. Tölle - One of the best experts on this subject based on the ideXlab platform.

  • Metabolic activity changes in the rat spinal cord during adjuvant Monoarthritis.
    Neuroscience, 1999
    Co-Authors: Jan Schadrack, Fani Neto, A. Ableitner, Frode Willoch, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Thomas R. Tölle
    Abstract:

    Abstract The development of chronic pain is associated with activity-dependent plastic changes in neuronal structures in the peripheral and central nervous system. In order to investigate the time-dependent processing of afferent noxious stimuli in the spinal cord we employed the quantitative autoradiographic 2-deoxyglucose technique in a model of chronic monoarthritic pain in the rat. Spinal metabolic activity was determined at various time-points (two, four and 14 days) after the injection of complete Freund's adjuvant into the left tibiotarsal joint. In addition, the effect of acute noxious mechanical stimulation of the arthritic joint was investigated at 14 days of Monoarthritis. Local glucose utilization was determined in lumbar segments L 2 –L 5 , ipsi- and contralateral to the inflamed hindpaw, and compared with saline-injected controls. In general, monoarthritic animals had bilaterally increased metabolic activity in all laminae of the spinal cord. Detailing the time-course showed that in rats with two days of Monoarthritis metabolic activity was significantly increased to a similar extent on both sides of all spinal laminae. In contrast, at four days, glucose utilization in deep laminae of the dorsal horn (laminae V–VI), the central gray area (laminae X) and the ventral horn (laminae VII–IX) tended to return to control levels. At 14 days of Monoarthritis, however, metabolic activity showed a further increase in all laminae of the spinal cord. This increase was more pronounced on the side ipsilateral to inflammation, reaching 65% above corresponding control levels in laminae V, VI. Animals with 14 days of Monoarthritis which were subjected to mechanical noxious stimulation of the arthritic joint displayed clear behavioral signs of acute pain. Although in this group metabolic activity was above control levels, it was lower than in animals with 14 days of Monoarthritis that were not additionally stimulated. The data show not only a general increase of spinal cord metabolic activity during the time-course of the development of a chronic pain state, but also show a region-specific non-linear time profile. This may reflect the complexity of transducing and suppressive transmitter systems involved in the central processing of ongoing pain.

  • Supraspinal metabolic activity changes in the rat during adjuvant Monoarthritis
    Neuroscience, 1999
    Co-Authors: Fani Neto, A. Ableitner, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Jan Schadrack, Thomas R. Tölle
    Abstract:

    Abstract Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic Monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during Monoarthritis were assessed using the quantitative [ 14 C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of Monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day Monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of Monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. 112 The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful Monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the Monoarthritis and accompanying its development.

  • Supraspinal metabolic activity changes in the rat during adjuvant Monoarthritis
    Neuroscience, 1999
    Co-Authors: Fani Neto, A. Ableitner, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Jan Schadrack, Thomas R. Tölle
    Abstract:

    Abstract Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic Monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during Monoarthritis were assessed using the quantitative [ 14 C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of Monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day Monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of Monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. 112 The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful Monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the Monoarthritis and accompanying its development.

Fani Neto - One of the best experts on this subject based on the ideXlab platform.

  • Reversal of Monoarthritis-induced affective disorders by diclofenac in rats.
    Anesthesiology, 2014
    Co-Authors: Gisela Borges, Fani Neto, Juan Antonio Micó, Esther Berrocoso
    Abstract:

    BACKGROUND Nonsteroidal anti-inflammatory drugs are effective for arthritic pain, but it is unknown whether they also benefit anxiety and depression that frequently coexist with pain. Using the Monoarthritis model, the authors evaluated the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in structures implicated in both sensorial and emotional pain spheres, and it was verified whether analgesia can reverse Monoarthritis-mediated affective responses. METHODS Monoarthritis was induced in male rats by complete Freund's adjuvant injection. Allodynia (ankle-bend test), mechanical hyperalgesia (paw-pinch test), anxiety- and depression-like behaviors (elevated zero maze and forced swimming tests, respectively), and ERK1/2 phosphorylation (Western blot) in the spinal cord, paragigantocellularis nucleus, locus coeruleus, and prefrontal cortex were evaluated at 4, 14, and 28 days postinoculation (n = 6 per group). Changes in these parameters were evaluated after induction of analgesia by topical diclofenac (n = 5 to 6 per group). RESULTS Despite the pain hypersensitivity and inflammation throughout the testing period, chronic Monoarthritis (28 days) also resulted in depressive- (control [mean ± SEM]: 38.3 ± 3.7 vs. Monoarthritis: 51.3 ± 2.0; P < 0.05) and anxiogenic-like behaviors (control: 36.8 ± 3.7 vs. Monoarthritis: 13.2 ± 2.9; P < 0.001). These changes coincided with increased ERK1/2 activation in the spinal cord, paragigantocellularis, locus coeruleus, and prefrontal cortex (control vs. Monoarthritis: 1.0 ± 0.0 vs. 5.1 ± 20.8, P < 0.001; 0.9 ± 0.0 vs. 1.9 ± 0.4, P < 0.05; 1.0 ± 0.3 vs. 2.9 ± 0.6, P < 0.01; and 1.0 ± 0.0 vs. 1.8 ± 0.1, P < 0.05, respectively). Diclofenac decreased the pain threshold of the inflamed paw and reversed the anxio-depressive state, restoring ERK1/2 activation levels in the regions analyzed. CONCLUSION Chronic Monoarthritis induces affective disorders associated with ERK1/2 phosphorylation in paragigantocellularis, locus coeruleus, and prefrontal cortex which are reversed by diclofenac analgesia. (Anesthesiology 2014; 120:1476-90).

  • Metabolic activity changes in the rat spinal cord during adjuvant Monoarthritis.
    Neuroscience, 1999
    Co-Authors: Jan Schadrack, Fani Neto, A. Ableitner, Frode Willoch, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Thomas R. Tölle
    Abstract:

    Abstract The development of chronic pain is associated with activity-dependent plastic changes in neuronal structures in the peripheral and central nervous system. In order to investigate the time-dependent processing of afferent noxious stimuli in the spinal cord we employed the quantitative autoradiographic 2-deoxyglucose technique in a model of chronic monoarthritic pain in the rat. Spinal metabolic activity was determined at various time-points (two, four and 14 days) after the injection of complete Freund's adjuvant into the left tibiotarsal joint. In addition, the effect of acute noxious mechanical stimulation of the arthritic joint was investigated at 14 days of Monoarthritis. Local glucose utilization was determined in lumbar segments L 2 –L 5 , ipsi- and contralateral to the inflamed hindpaw, and compared with saline-injected controls. In general, monoarthritic animals had bilaterally increased metabolic activity in all laminae of the spinal cord. Detailing the time-course showed that in rats with two days of Monoarthritis metabolic activity was significantly increased to a similar extent on both sides of all spinal laminae. In contrast, at four days, glucose utilization in deep laminae of the dorsal horn (laminae V–VI), the central gray area (laminae X) and the ventral horn (laminae VII–IX) tended to return to control levels. At 14 days of Monoarthritis, however, metabolic activity showed a further increase in all laminae of the spinal cord. This increase was more pronounced on the side ipsilateral to inflammation, reaching 65% above corresponding control levels in laminae V, VI. Animals with 14 days of Monoarthritis which were subjected to mechanical noxious stimulation of the arthritic joint displayed clear behavioral signs of acute pain. Although in this group metabolic activity was above control levels, it was lower than in animals with 14 days of Monoarthritis that were not additionally stimulated. The data show not only a general increase of spinal cord metabolic activity during the time-course of the development of a chronic pain state, but also show a region-specific non-linear time profile. This may reflect the complexity of transducing and suppressive transmitter systems involved in the central processing of ongoing pain.

  • Supraspinal metabolic activity changes in the rat during adjuvant Monoarthritis
    Neuroscience, 1999
    Co-Authors: Fani Neto, A. Ableitner, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Jan Schadrack, Thomas R. Tölle
    Abstract:

    Abstract Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic Monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during Monoarthritis were assessed using the quantitative [ 14 C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of Monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day Monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of Monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. 112 The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful Monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the Monoarthritis and accompanying its development.

  • Supraspinal metabolic activity changes in the rat during adjuvant Monoarthritis
    Neuroscience, 1999
    Co-Authors: Fani Neto, A. Ableitner, Walter Zieglgänsberger, José Manuel Castro-lopes, Peter Bartenstein, Jan Schadrack, Thomas R. Tölle
    Abstract:

    Abstract Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic Monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during Monoarthritis were assessed using the quantitative [ 14 C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of Monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day Monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of Monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. 112 The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful Monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the Monoarthritis and accompanying its development.

Weishi Zhang - One of the best experts on this subject based on the ideXlab platform.

  • evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of Monoarthritis
    Clinical and Experimental Pharmacology and Physiology, 2010
    Co-Authors: Weishi Zhang, Jia Le Yang, Xiaoming Deng, Yuqiu Zhang
    Abstract:

    Summary 1. Spinal glial cells play a key role in developing and maintaining allodynia and hyperalgesia following tissue inflammation. Dexmedetomidine, a highly selective α2-adrenoceptor (α2-AR) agonist, has exhibited a significant analgesic effect in various rodent models of chronic pain. However, whether spinal glial activation is involved in the analgesic effect of dexmedetomidine remains unknown. The present study investigated whether spinal administration of dexmedetomidine could antagonize glial activation in the spinal dorsal horn and attenuate thermal hyperalgesia in complete Freund’s adjuvant (CFA)-induced ankle joint monoarthritic (MA) rats. 2. Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Repeated lumbar puncture (LP) administration of dexmedetomidine (10 μg) significantly attenuated MA-induced thermal hyperalgesia in a cumulative manner. Monoarthritis-induced spinal glial activation was also suppressed following dexmedetomidine application. The α2A-AR, essential for the antinociceptive effects of α2-AR agonists, was detected in spinal neurons and glia, as well as in dorsal root ganglion primary afferent neurons, which may be implicated in dexmedetomidine-induced suppression of spinal glial activation and antihyperalgesic effects. 3. These data provide the first evidence that blocking spinal glial activation is involved in the analgesic action of dexmedetomidine.

  • dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of Monoarthritis
    Acta Pharmacologica Sinica, 2010
    Co-Authors: Weishi Zhang, Jia Le Yang, Xiaoming Deng, Yuqiu Zhang
    Abstract:

    To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (α2AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by Monoarthritis (MA). MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 μg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.

Wei-yi Gong - One of the best experts on this subject based on the ideXlab platform.

  • Chronic Monoarthritis Pain Accelerates the Processes of Cognitive Impairment and Increases the NMDAR Subunits NR2B in CA3 of Hippocampus from 5-month-old Transgenic APP/PS1 Mice.
    Frontiers in aging neuroscience, 2017
    Co-Authors: Wei-yi Gong, Rong Wang, Yuan Liu, He Jin, Zhiwei Zhao, Yu-lan Wang, Xu Zhang
    Abstract:

    Many factors impact cognitive impairment; however, the effects of chronic pain and the mechanisms underlying these effects on cognitive impairment are currently unknown. Here we tested the hypothesis that chronic pain accelerates the transition from normal cognition to mild cognitive impairment in 5-month-old transgenic APP/PS1 mice, an animal model of Alzheimer’s disease, and that neurotoxicity induced by N-methyl-D-aspartic acid receptor (NMDAR) subunits may be involved in this process. Chronic Monoarthritis pain was induced in transgenic APP/PS1 mice and 5-month-old wild-type mice by intra- and pre-articular injections of Freund’s complete adjuvant into one knee joint. Pain behavior, learning and memory function, and the distribution and quantity of NMDAR subunits (NR1, NR2A and NR2B) in hippocampal CA1 and CA3 regions were assessed. Our results showed that although persistent and robust Monoarthritis pain was induced by the Freund’s complete adjuvant injections, only the transgenic APP/PS1 mice with chronic Monoarthritis pain exhibited marked learning and memory impairments. This result suggested that chronic Monoarthritis pain accelerated the cognitive impairment process. Furthermore, only transgenic APP/PS1 mice with chronic Monoarthritis pain exhibited an overexpression of NR2B and an increased NR2B/NR2A ratio in the hippocampus CA3. These findings suggest that chronic pain is a risk factor for cognitive impairment and that increased neurotoxicity associated with NMDAR subunit activation may underpin the impairment. Thus, NMDARs may be a therapeutic target for the prevention of chronic pain-induced cognitive impairment.

  • Chronic Monoarthritis Pain Accelerates the Processes of Cognitive Impairment and Increases the NMDAR Subunits NR2B in CA3 of Hippocampus from 5-month-old Transgenic APP/PS1 Mice
    Frontiers Media S.A., 2017
    Co-Authors: Wei-yi Gong, Rong Wang, Yuan Liu, He Jin, Zhiwei Zhao, Yu-lan Wang
    Abstract:

    Many factors impact cognitive impairment; however, the effects of chronic pain and the mechanisms underlying these effects on cognitive impairment are currently unknown. Here we tested the hypothesis that chronic pain accelerates the transition from normal cognition to mild cognitive impairment (MCI) in 5-month-old transgenic APP/PS1 mice, an animal model of Alzheimer’s disease (AD), and that neurotoxicity induced by N-methyl-D-aspartic acid receptor (NMDAR) subunits may be involved in this process. Chronic Monoarthritis pain was induced in transgenic APP/PS1 mice and 5-month-old wild-type (WT) mice by intra- and pre-articular injections of Freund’s complete adjuvant (FCA) into one knee joint. Pain behavior, learning and memory function, and the distribution and quantity of NMDAR subunits (NR1, NR2A and NR2B) in hippocampal CA1 and CA3 regions were assessed. Our results showed that although persistent and robust Monoarthritis pain was induced by the FCA injections, only the transgenic APP/PS1 mice with chronic Monoarthritis pain exhibited marked learning and memory impairments. This result suggested that chronic Monoarthritis pain accelerated the cognitive impairment process. Furthermore, only transgenic APP/PS1 mice with chronic Monoarthritis pain exhibited an overexpression of NR2B and an increased NR2B/NR2A ratio in the hippocampus CA3. These findings suggest that chronic pain is a risk factor for cognitive impairment and that increased neurotoxicity associated with NMDAR subunit activation may underpin the impairment. Thus, NMDARs may be a therapeutic target for the prevention of chronic pain-induced cognitive impairment