Nociception in cyclooxygenase isozyme-deficient mice

Ballou, Leslie R.; Botting, Regina M.; Goorha, Salil; Zhang, Jianyi; Vane, John R.

doi:10.1073/pnas.180319297

Cited by 190 publications

(119 citation statements)

References 29 publications

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“…In the acetic acid writhing model of inflammatory hyperalgesia, using COX-1-and COX-2-deficient mice, COX-1 appears to be a major contributor of the response, with COX-2 contributing a relatively minor component (38). In this present study, PGE 2 levels were significantly reduced in the acetic acid-treated mPGES1 Ϫ/Ϫ animals compared with controls.…”

Section: Resultssupporting

confidence: 51%

Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase

Trebino

Stock

Gibbons

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

510

478

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Prostaglandin (PG)E2 is a potent mediator of pain and inflammation, and high levels of this lipid mediator are observed in numerous disease states. The inhibition of PGE2 production to control pain and to treat diseases such as rheumatoid arthritis to date has depended on nonsteroidal antiinflammatory agents such as aspirin. However, these agents inhibit the synthesis of all prostanoids. To produce biologically active PGE2, PGE synthases catalyze the isomerization of PGH2 into PGE2. Recently, several PGE synthases have been identified and cloned, but their role in inflammation is not clear. To study the physiological role of the individual PGE synthases, we have generated by targeted homologous recombination a mouse line deficient in microsomal PGE synthase 1 (mPGES1) on the inbred DBA͞1lacJ background. mPGES1-deficient (mPGES1 ؊/؊ ) mice are viable and fertile and develop normally compared with wild-type controls. However, mPGES1 ؊/؊ mice displayed a marked reduction in inflammatory responses compared with mPGES1 ؉/؉ mice in multiple assays. Here, we identify mPGES1 as the PGE synthase that contributes to the pathogenesis of collagen-induced arthritis, a disease model of human rheumatoid arthritis. We also show that mPGES1 is responsible for the production of PGE 2 that mediates acute pain during an inflammatory response. These findings suggest that mPGES1 provides a target for the treatment of inflammatory diseases and pain associated with inflammatory states.arthritis ͉ inflammation ͉ macrophage ͉ knockout ͉ PGE2

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Section: Resultssupporting

confidence: 51%

Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase

Trebino

Stock

Gibbons

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

510

478

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“…This was performed as described previously (Ballou et al, 2000). Mice were individually placed at the center of the heated flat surface (25 Â 25 cm; 551C) of an Analgesia Meter (Columbus Instrument, Columbus, OH) and removed immediately after they licked the footpad of the hind paw.…”

Section: Measurement Of Nociceptive Responsesmentioning

confidence: 99%

Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)

Zhang

Huang

Masood

et al. 2007

Neuropsychopharmacol

157

143

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Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression-and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4BÀ/À). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4BÀ/À mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4BÀ/À mice. Compared to PDE4B + / + littermates, PDE4BÀ/À mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light-dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4BÀ/À mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4BÀ/À mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4BÀ/À mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior.

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“…Strain C57/DBA1 of wild-type, PGHS-1 null, and PGHS-2 null mice used in these studies were developed at the Department of Veterans Affairs Medical Center in Memphis (Ballou et al, 2000) from mating pairs that originated at the University of North Carolina Morham et al, 1995). Before experiments, animals were housed in Plexiglas cages at 25°C and kept on a 12-hour light/12 hour dark cycle in a virus-free environment.…”

Section: Animalsmentioning

confidence: 99%

“…Because of fertility problems of the PGHS null mice, homozygous males were bred with heterozygous females to obtain the homozygous female mice used in all experiments. The genotypes of the animals were determined by PCR (Ballou et al, 2000).…”

Section: Animalsmentioning

confidence: 99%

“…Internal standards for RT-PCR of PGHS-1 and PGHS-2 were created as described elsewhere (Ballou et al, 2000) such that PCR products from cRNAs for PGHS-1 and PGHS-2 could be generated using the same deoxyoligonucleotide primers as for mRNAs in the RT-PCR reactions. The PGHS-1 cRNA product contained a 165-bp internal deletion (ϩ1517 to ϩ1681) of the PGHS-1 mRNA RT-PCR product (ϩ1496 to ϩ2097), and the PGHS-2 cRNA product contained a 131-bp internal deletion (ϩ1351 to ϩ1481) of the PGHS-2 mRNA RT-PCR product (ϩ1227 to ϩ1500).…”

Section: Rt-pcr Analysis Of Wound Site Rnamentioning

confidence: 99%

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Both Constitutive and Inducible Prostaglandin H Synthase Affect Dermal Wound Healing in Mice

Laulederkind

Thompson-Jaeger

Goorha

et al. 2002

Laboratory Investigation

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SUMMARY:In an attempt to define the roles of prostaglandin H synthase 1 (PGHS-1, cyclooxygenase-1, COX-1) and prostaglandin H synthase 2 (PGHS-2, cyclooxygenase-2, COX-2) in wound healing, we investigated the healing of incisional dermal wounds in wild-type, PGHS-1 null, and PGHS-2 null mice. We measured tensile strength of the wounds, levels of PGHS-1 and PGHS-2 mRNA in the wound site, and histologic markers for the inflammatory, proliferative, and remodeling phases of wound healing. Although no gross visible differences were noted among healed wounds of the different mouse types, measurement of tensile strength showed that both PGHS-1 and PGHS-2 null wounds were weaker (75% and 70%, respectively) than wild-type wounds at 12 days after incision. At Day 8 the endothelial staining was 70% greater in the wounds of PGHS-2 null mice compared with their wild-type counterparts. In contrast at Day 12, staining for macrophages and myofibroblasts was less in PGHS-1 null wounds compared with wild-type and PGHS-2 null tissue. Compensatory expression of the alternate PGHS mRNA could be demonstrated by RT-PCR in the wounds of PGHS null mice on Days 1 and 4. We conclude that both PGHS-1 and PGHS-2 genes play distinct roles in the process of dermal wound healing. (Lab Invest 2002, 82:919 -927).

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Nociception in cyclooxygenase isozyme-deficient mice

Cited by 190 publications

References 29 publications

Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase

Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase

Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)

Both Constitutive and Inducible Prostaglandin H Synthase Affect Dermal Wound Healing in Mice

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