Etodolac Attenuates Hippocampal Blood Flow Responses Induced by Tooth Pulp Stimulation in Rats

Makoto Hasegawa, Junichi Hada, Tetsuya Abe, Nao Ohtsu, Kousuke Honda, Masahiro Urade

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DOI: 10.4236/nm.2011.23038                

Abstract

In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (MABP) and HBF in urethane-anesthetized rats using laser Doppler flowmetry and examined the effects of etodolac, a specific COX-2 inhibitor, on TPS-induced MABP and HBF responses. The MABP response was not attenuated by the intraperitoneal (i.p.) administration of etodolac (10 mg/kg); however, the HBF response was significantly attenuated by etodolac administration. These results suggest that COX-2 may be involved in the mechanisms regulating TPS-induced HBF responses.

Keywords

Cyclooxygenase-2 (COX-2), Etodolac, Fear Memory, Hippocampal Blood Flow, Mean Arterial Blood Pressure, Tooth Pulp Stimulation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. Ploghaus, C. Narain, C. F. Beckmann, S. Clare, S. Bantick, R. Wise, P. M. Matthews, J. N. P. Rawlins and I. Tracey, “Extracerbation of Pain by Anxiety is Associated with Activity in a Hippocampal Network,” Journal of Neuroscience, Vol. 21, No. 24, 2001, pp. 9896-9903.
[2]	K. Okawa, T. Ichinohe and Y. Kaneko, “Anxiety May Enhance Pain during Dental Treatment,” The Bulletin of Tokyo Dental College, Vol. 46, No. 3, 2005, pp. 51-58.
[3]	M. Funahashi, Y.-F. He, T. Sugimoto and R. Matsuo, “Noxious Tooth Pulp Stimulation Suppresses c-fos Expression in the Rat Hippcampal Formation,” Brain Research, Vol. 827, 1999, pp. 215-220.
[4]	M. Hasegawa, J. Hada, T. Abe, K. Honda, A. Shimizu and M. Urade, “Theophylline Attenuates Hippocampal Blood Flow Responses Induced by Tooth Pulp Stimulation in Rats,” Neuroscience Research, Vol. 65, No. 2, 2009, pp. 156-159.
[5]	K. Caesar, N. Akgoren, C. Mathiesen and M. Lariyzen, “Modification of Activity-dependent Increases in Cerebellar Blood Flow by Extracellular Potassium in Anaesthetized Rats,” Journal of Physiology, Vol. 520, No. 1, 1999, pp. 281-292.
[6]	U. Lindauer, D. Megow, H. Matsuda, and U. Dirnagl, “Nitric Oxide: A Modulator, But Not a Mediator, of Neurovascular Coupling in Rat Somatosensory Cortex,” American Journal of Physiology, Vol. 277, No. 2, 1999, pp. H799-H811.
[7]	M. Zonta, M. C. Angulo, S. Gobbo, B. Rosengarten, K.-A. Hossman, T. Pozzan, and G. Carmignoto, “Neuron-to- Astrocyte Signaling is Central to the Dynamic Control of Brain Microcirculation,” Nature Neuroscience, Vol. 6, No. 1, 2003, pp. 43-50.
[8]	H. Suyama, M. Kawamoto, S. Gaus, and O. Yuge, “Effect of Etodolac, a COX-2 Inhibitor, on Neuropathic Pain in a Rat Model,” Brain Research, Vol. 1010, No. 1-2, 2004, pp. 144-150.
[9]	K. Niwa, E. Araki, S. G. Morham, M. E. Ross and C. Iadecola, “Cyclooxygenase-2 Contributes to Functional Hyperemia in Whisker-barrel Cortex,” Journal of Neuroscience, Vol. 20, No. 2, 2000, pp. 763-770.
[10]	R. N. Dubois, S. B. Abramson, L. Grottrd, R. A. Gupta, L. S. Simon, L. B. A. van de Putte and P. E. Lipsky, “Cyclooxygenase in Biology and Disease,” The FASEB Journal, Vol. 12, No. 12, 1998, pp. 1063-1073.
[11]	W. E. Kaufmann, P. F. Worley, J. Pegg, M. Bremer, and P. Isakson, “COX-2, a Synaptically Induced Enzyme, Is Expressed by Excitatory Neurons at Postsynaptic Sites in Rat Cerebral Cortex,” Proceeding of the National Academy of Sciences of the United States of America, Vol. 93, No. 6, 1996, pp. 2317-2321.
[12]	A. J. Gelsema, D. J. Mckitrick and F. R. Calaresu, “Cardiovascular Responses to Chemical and Electrical Stimulation of Amygdala in Rats,” American Journal of Physiology, Vol. 253, No. 5, 1987, pp. R712-R718.
[13]	T. Seidenbecher, T. R. Laxmi, O. Stork and H.-C. Page, “Synchronization of Amygdalar and Hippocampal Theta Oscillations during Retrieval of Pavlovian Fear Memory,” Science, Vol. 301, No. 5634, 2003, pp. 846-850.