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Intratrigeminal ganglionic injection of LPA causes neuropathic pain-like behavior and demyelination in rats

Ahn, Dong K.a,*; Lee, Sang Y.a; Han, Seung R.a; Ju, Jin S.a; Yang, Gwi Y.a; Lee, Min K.a; Youn, Dong H.a; Bae, Yong C.b

doi: 10.1016/j.pain.2009.07.012
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ABSTRACT We have previously reported a novel method for producing chronic nociceptive behavior in rats following compression of the trigeminal ganglion. In the present study, we have further studied the role of demyelination in the development of prolonged nociceptive behavior in the trigeminal territory. For this purpose, lysophosphatidic acid (LPA) was injected into the trigeminal ganglia of male Sprague–Dawley rats weighing between 250 and 260 g. Under pentobarbital sodium anesthesia, the rats were mounted onto a stereotaxic frame and 3 μL of LPA (1 nmol) solution was injected into the trigeminal ganglion to produce demyelination. This treatment decreased the air-puff thresholds both ipsilateral and contralateral to the injection site, which persisted until postoperative day 100 and returned to the preoperative levels 130 days after the LPA injection. The LPA injection also produced a significant ipsilateral hyper-responsiveness to pin-prick stimulation. The effects of DGPP, an LPA1/3 receptor antagonist, and Y-27632, a Rho kinase inhibitor, upon LPA-induced mechanical allodynia and hyperalgesia were also investigated. Pretreatment with DGPP blocked both mechanical allodynia and ipsilateral hyperalgesia. However, pretreatment with Y-27632 blocked only ipsilateral and contralateral mechanical allodynia. These results thus indicate that a targeted blockade of LPA receptor and Rho kinase pathways are potentially important new treatments for demyelination-induced trigeminal neuralgia-like nociception.

aDepartment of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea

bDepartment of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea

*Corresponding author. Address: Department of Oral Physiology, School of Dentistry, Kyungpook National University, 188-1 Sam Deok 2ga, Chung-gu, Daegu 700-412, Republic of Korea. Tel.: +82 53 660 6840; fax: +82 53 421 4077.

E-mail: dkahn@knu.ac.kr

Received February 11, 2009; Received in revised form July 7, 2009; Accepted July 13, 2009.

© 2009 Lippincott Williams & Wilkins, Inc.
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