Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats

Cao, Hong; Zang, Kaikai; Han, Mei; Zhao, Zhi‐Qi; Wu, Gen-Cheng; Zhang, Yu‐Qiu

doi:10.1016/j.brainresbull.2014.06.005

Cited by 18 publications

(13 citation statements)

References 46 publications

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“…LPS activation renders microglia ameboid, induces several pro-and antiinflammatory signaling molecules (Lim et al, 2015;Zhu et al, 2014) and neurotoxic substances through binding to the CD14/MD-2/Toll-like receptor 4-complex (Fricker et al, 2012;Tokes et al, 2011), and gives rise, among others, to cell spreading by interfering with the organization of the actin cytoskeleton through the alteration of integrin clustering (Abram and Lowell, 2009). Microglia activation was shown to involve the signaling pathways nuclear factor B and p38 mitogenactivated protein kinase (Bachstetter et al, 2007;Cao et al, 2014;Kaushal et al, 2007). It must be noted, however, that the activation of microglial cells by LPS is not proliferative (Suzumura et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Calmodulin inhibition regulates morphological and functional changes related to the actin cytoskeleton in pure microglial cells

Szabó

Dulka

Gulya

2016

Brain Research Bulletin

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The roles of calmodulin (CaM), a multifunctional intracellular calcium receptor protein, as concerns selected morphological and functional characteristics of pure microglial cells derived from mixed primary cultures from embryonal forebrains of rats, were investigated through use of the CaM antagonists calmidazolium (CALMID) and trifluoperazine (TFP). The intracellular localization of the CaM protein relative to phalloidin, a bicyclic heptapeptide that binds only to filamentous actin, and the ionized calcium-binding adaptor molecule 1 (Iba1), a microglia-specific actin-binding protein, was determined by immunocytochemistry, with quantitative analysis by immunoblotting. In unchallenged and untreated (control) microglia, high concentrations of CaM protein were found mainly perinuclearly in ameboid microglia, while the cell cortex had a smaller CaM content that diminished progressively deeper into the branches in the ramified microglia. The amounts and intracellular distributions of both Iba1 and CaM proteins were altered after lipopolysaccharide (LPS) challenge in activated microglia. CALMID and TFP exerted different, sometimes opposing, effects on many morphological, cytoskeletal and functional characteristics of the microglial cells. They affected the CaM and Iba1 protein expressions and their intracellular localizations differently, inhibited cell proliferation, viability and fluid-phase phagocytosis to different degrees both in unchallenged and in LPS-treated (immunologically challenged) cells, and differentially affected the reorganization of the actin cytoskeleton in the microglial cell cortex, influencing lamellipodia, filopodia and podosome formation. In summary, these CaM antagonists altered different aspects of filamentous actin-based cell morphology and related functions with variable efficacy, which could be important in deciphering the roles of CaM in regulating microglial functions in health and disease.

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Section: Discussionmentioning

confidence: 99%

Calmodulin inhibition regulates morphological and functional changes related to the actin cytoskeleton in pure microglial cells

Szabó

Dulka

Gulya

2016

Brain Research Bulletin

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“…NSAIDs have also been shown to reverse pain-related depression of motivated behavior in the ICSS platform [Leitl et al, 2014] and the conditioned place preference procedure [Rutten et al, 2011]. In the latter example, a range of analgesic drugs, including the NSAID indomethacin, attenuated a carrageenaninduced conditioned place aversion [Cao et al, 2014]. Both CPP and CPA are thought to measure aspects of the affective components of pain-like states in rodents [Johansen and Fields 2004;Xie et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Postoperative Pain‐Like State on Motivated Behavior in Rats: Effects of Plantar Incision on Progressive‐Ratio Food‐Maintained Responding

Warner

Krivitsky

Cone

et al. 2015

Drug Development Research

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There has been recent interest in characterizing the effects of pain-like states on motivated behaviors in order to quantify how pain modulates goal-directed behavior and the persistence of that behavior. The current set of experiments assessed the effects of an incisional post-operative pain manipulation on food-maintained responding under a progressive-ratio (PR) operant schedule. Independent variables included injury state (plantar incision or anesthesia control) and reinforcer type (grain pellet or sugar pellet); dependent variables were tactile sensory thresholds and response breakpoint. Once responding stabilized on the PR schedule, separate groups of rats received a single ventral hind paw incision or anesthesia (control condition). Incision significantly reduced breakpoints in rats responding for grain, but not sugar. In rats responding for sugar, tactile hypersensitivity recovered within 24 hrs, indicating a faster recovery of incision-induced tactile hypersensitivity compared to rats responding for grain, which demonstrated recovery at PD2. The NSAID analgesic, diclofenac (5.6 mg/kg) completely restored incision-depressed PR operant responding and tactile sensitivity at 3 hr following incision. The PR schedule differentiated between sucrose and grain, suggesting that relative reinforcing efficacy may be an important determinant in detecting pain-induced changes in motivated behavior.

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“…Therefore one of the objectives of the present work was to determine the capability of 14-O-MeM6SU to produce analgesic tolerance in mice chronically treated with morphine or 14-O-MeM6SU. Prefrontal cortical neurons beside their role in the emotional components of pain are also critically involved in withdrawal, reward and tolerance development as indicated by in in vivo and in vitro studies (Cao et al, 2014;Wu et al, 2013). Thus we have also measured the effect of 14-O-MeM6SU on spontaneous excitatory postsynaptic currents (sEPSCs) in layer V pyramidal cells of rat prefrontal cortical slices, compared to morphine to clarify how the new compound may affect glutamatergic transmission.…”

Section: Introductionmentioning

confidence: 98%

A new potent analgesic agent with reduced liability to produce morphine tolerance

Király¹,

Caputi²,

Hanuska³

et al. 2015

Brain Research Bulletin

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Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats

Cited by 18 publications

References 46 publications

Calmodulin inhibition regulates morphological and functional changes related to the actin cytoskeleton in pure microglial cells

Calmodulin inhibition regulates morphological and functional changes related to the actin cytoskeleton in pure microglial cells

Evaluation of a Postoperative Pain‐Like State on Motivated Behavior in Rats: Effects of Plantar Incision on Progressive‐Ratio Food‐Maintained Responding

A new potent analgesic agent with reduced liability to produce morphine tolerance

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