A novel trigeminal neuropathic pain model: Compression of the trigeminal nerve root produces prolonged nociception in rats

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2012-08, Vol.38 (2), p.149-158
• Main Authors: Jeon, Hye J., Han, Seung R., Park, Min K., Yang, Kui Y., Bae, Yong C., Ahn, Dong K.
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Behavior, Animal - physiology; Biological and medical sciences; Carbamazepine; Disease Models, Animal; Facial Pain - physiopathology; Hyperalgesia; Hyperalgesia - physiopathology; Male; Medical sciences; Neuralgia - physiopathology; Neuropathic pain; Neuropharmacology; Nociception - physiology; Pain Measurement; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion - physiology; Trigeminal Nerve - physiopathology; Trigeminal neuralgia
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2012.03.002

We demonstrate the establishment of a novel animal model for trigeminal neuropathic pain following compression of the trigeminal nerve root, which produces prolonged nociceptive behavior and demyelination of the trigeminal nerve root. Under anesthesia, male Sprague–Dawley rats (200–230g) were mounted onto a stereotaxic frame and injections of a 4% agar solution (10μl) were given to achieve compression of the trigeminal nerve root. A sham operation was performed using identical procedures but without agar injections. Nociceptive behavior was examined 3days before and then at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70days after the surgery. Compression of the trigeminal nerve root caused mechanical allodynia, hyperalgesia, and cold hypersensitivity. Mechanical allodynia was established within 3days and recovered to preoperative levels on postoperative day (POD) 40. Mechanical hyperalgesia and cold hypersensitivity persisted until 55days following compression. The compression produced focal demyelination in the trigeminal nerve root. In the medullary dorsal horn, phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) was found to be exclusively expressed in the microglia on POD 14. Furthermore, intraperitoneal administration of carbamazepine (50mg/kg) significantly blocked mechanical allodynia and reduced p38 MAPK activation induced by the compression of the trigeminal nerve root. Our findings suggest that prolonged nociceptive behavior following compression of the trigeminal nerve root may mimic trigeminal neuralgia in this animal model and that the activation of p38 MAPK in the microglia contributes to pain hypersensitivity in rats that have undergone compression of the trigeminal nerve root. ►Compression of trigeminal nerve root produces nociceptive behavior and p38 activation.► P-p38 expression is found to be predominantly co-localized in the microglia. ► Carbamazepine attenuates both mechanical allodynia and up-regulated p-p38.