Intratrigeminal ganglionic injection of LPA causes neuropathic pain-like behavior and demyelination in rats.
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 microL 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.
Ahn
Dong K
DK
Department of Oral Physiology, School of Dentistry, Kyungpook National University, 188-1 Sam Deok 2ga, Chung-gu, Daegu 700-412, Republic of Korea. dkahn@knu.ac.kr
Lee
Sang Y
SY
Han
Seung R
SR
Ju
Jin S
JS
Yang
Gwi Y
GY
Lee
Min K
MK
Youn
Dong H
DH
Bae
Yong C
YC
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D007267:Injections; D008246:Lysophospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010146:Pain / Q000139:chemically induced* / Q000523:psychology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000523:psychology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics; D012668:Trigeminal Ganglion / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D054460:rho-Associated Kinases; C032881:lysophosphatidic acid