Background and aims: Sensitization of primary and secondary trigeminal sensory neurons underlies hyperalgesia and allodynia in orofacial pain and headache syndromes. Hemokinin-1 (HK-1) encoded by the Tac4 gene is the newest member of the tachykinin family. It has been suggested to play a role in nociceptor sensitization but it has not been investigated in facial pain models. Therefore, we aimed to investigate the expression of Tac4 mRNA in trigeminal ganglia (TRG) and compare wild-type and Tac4 gene-deficient mice in Complete Freund’s Adjuvant (CFA)-induced orofacial inflammation.
Methods: CFA was injected in the whisker pad of Wistar rats, C57Bl/6 or Tac4 gene-deleted mice. Mechanical pain thresholds of the face were determined with von Frey filaments. Gene expression changes in TRG were measured by quantitative PCR at different time points after inflammation.
Results: In rats, orofacial mechanical allodynia developed by day 1 after CFA injection with a maximum on day 3. The course of allodynia correlated with increased expression of Tac4, as well as neuronal and glial activation markers in the TRG. We could not reliably measure CFA-induced orofacial allodynia in mice. However, neuronal and glial activation markers were elevated at a lower extent in the TRG of Tac4 gene-deleted mice compared to wild-type animals. 
Conclusions: Expression of HK-1 was detected in TRG and it was upregulated after orofacial inflammation. The potential role of HK-1 in sensitization of trigeminal afferents is supported by reduced neuronal and glial activation in Tac4 gene-deficient mice. 

Acknowledgements: The study was supported by grants KTIA_NAP_13-2014-0022, GINOP-2.3.2-15-2016-00048, NTP-NFTÖ-18-B-0455, EFOP-3.6.3-VEKOP-16-2017-00009.

INVOLVEMENT OF HEMOKININ-1 IN TRIGEMINAL SENSITIZATION AFTER OROFACIAL INFLAMMATION