(PR09) Designer Receptors: A Novel Potential Therapeutic for Management of Trigeminal Neuropathic Pain

Abstract: Painful post traumatic trigeminal neuropathy (PTTN) is a Neuropathic pain (NP) disorder - presents as constant, dull, aching and burning pain. Following routine RCT (induces mild nerve injury), PTTN has been found in around 3% of patients. Transfection of a new class of receptors termed DREADDs into Trigeminal ganglion (TG) is an attractive therapeutic possibility.

Aims: To induce NP in a rat model via chronic constriction injury (CCI) to the infraorbital nerve (IoN), transfect rats’ TG cells with DREADDs and test for analgesic effect of activated DREADDs, by behavioral responses.

Methods: 44 rats were split in four experimental groups: IoN-CCI and injected with active DREADDs into ipsilateral TG; IoN-CCI and injected with control DREADDs into the ipsilateral TG; naive animals injected unilaterally with active DREADDs into TG and naive animals injected unilaterally with control DREADDs into the TG. The Von Frey Hypersensitivity (VFH) was used to assess ‘Tactile allodynia’ and Pinprick hypersensitivity was used to assess ‘Mechanical hyperalgesia’. Data were analyzed by Student’s t-test and Wilcoxon/Kruskal Wallis test (p < 0.05).

Results: It was observed that the CNO mediated activation of DREADDs transduced into the ipsilateral TG resulted in alleviation of VFH following IoN-CCI and significant reduction in the pinprick response score.

Conclusion: CNO-mediated activation of DREADDs attenuates pain-like behavior in rats with NP. DREADDS can be as effective in managing NP as centrally acting drugs, without any systemic side-effects.