Skip to main content

Volume 10 Supplement 1

Proceedings of the Seventh Scientific Meeting of The TMJ Association

  • Oral presentation
  • Open access
  • Published:

Study of chronic orofacial pain with preclinical models


Chronic orofacial pain conditions such as trigeminal neuropathic pain, reflex sympathetic dystrophy of the face, and temporomandibular pain disorders are debilitating pain conditions. They are known to respond poorly to treatment including opioids in human patients. There is a pressing need to better understand the mechanisms of these chronic orofacial pain conditions so that new and effective therapeutic targets can be identify. To achieve this goal, preclinical animal models that well represent human chronic orofacial pain conditions are needed. In the present study we used two preclinical models of chronic orofacial pain, the chronic constriction nerve injury of the infraorbital nerve (ION-CCI model) and the oxaliplatin-induced orofacial pain (oxaliplatin model). We applied newly developed orofacial operant behavioral assessment to study orofacial pain and to test effects on Kv7.2 channel activators in alleviating orofacial pain in these animals.

Materials and methods

Male Sprague–Dawley rats (300–450 g) were used in this study. In the ION-CCI model a chronic constriction nerve injury was created using unilateral ligation of the infraorbital nerve. For oxoliplatin model of orofacial pain, oxaliplatin was administered to rats (i.p.) at 2 mg/kg per day for five consecutive days. Orofacial pain behaviors in responses to mechanical and cold stimuli were assessed by the orofacial operant behavioral assessment method. To test the effects of Kv7.2 activators in alleviating orofacial pain in these two preclinical models, retigabine or CF341 was administered to these animals at the doses ranging from 0.19 to 15 mg.


Rats of both ION-CCI model and oxaliplatin model showed significant orofacial mechanical allodynia and cold allodynia/hyperalgesia as examined by using the orofacial operant assessment method. Retigabine, a classical Kv7.2 channel activator, significantly alleviated orofacial cold allodynia in both ION-CCI model and oxaliplatin model. CF341, a newly synthesized Kv7.2 channel activator, also showed alleviation of the orofacial cold allodynia with efficacy similar to retigabine.


In both ION-CCI model and oxaliplatin model, orofacial operant behavioral assessment gives quantitative measurements of chronic orofacial pain and therapeutic effects of Kv7.2 activators. The preclinical models shown in this work are useful for both mechanistic study and drug development for chronic orofacial pain.


This work was supported by a NIH/NIDCR grant DE018661 to J.G.

Author information

Authors and Affiliations


Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit

The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

ABD-Elsayed, A., Kohan, K., Zuo, X. et al. Study of chronic orofacial pain with preclinical models. Mol Pain 10 (Suppl 1), O6 (2014).

Download citation

  • Published:

  • DOI: