P2X ₃ receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice

Ectopic pain in other orofacial regions develops with local inflammation in separated orofacial structures. However, the basis for the spreading of pain to adjacent orofacial areas after local inflammation is still unknown. In the present study, we determined if the P2X ₃ receptor (P2X ₃R) was associated with altered mechanical sensitivity of the whisker pad skin following complete Freund's adjuvant (CFA) injection into the lower lip. Mice with local inflammation induced by CFA injection into the lower lip demonstrated significant mechanical allodynia of whisker pad skin. The mechanical allodynia was reversed by P2X ₃R antagonist, A-317491 administration into whisker pad skin. The number of P2X ₃R and calcitonin gene-related peptide (CGRP) positive trigeminal ganglion (TG) neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip. CGRP protein expression in TG ipsilateral to CFA injection was also significantly greater than that of the saline-injected mice. The present findings suggest that induced CGRP by local inflammation in the lower lip increases P2X ₃R in TG neurons, the increased P2X ₃Rs are involved in the sensitization of primary afferent neurons in the whisker pad skin. This P2X ₃R overexpression may underlie ectopic mechanical allodynia in the whisker pad skin after CFA injection into the lower lip.