Local knockdown of Nav1.6 relieves pain behaviors induced by BmK I.

Voltage-gated sodium channels (VGSCs) in peripheral nociceptive sensory neurons are critical to transmit pain signals. BmK I purified from the venom of scorpion Buthus martensi Karsch (BmK) has been demonstrated to be the primary contributor of envenomation-associated pain. However, the role of distinct VGSCs such as Nav1.6 in the induction and maintenance of pain behaviors induced by BmK I was ambiguous. Herein, using molecular and behavioral approaches we investigated the mRNA and protein expression profiles of Nav1.6 in rat DRG after intraplantar injection of BmK I and tested the pain behaviors after knockdown of Nav1.6 in BmK I-treated rats. It was shown that during induction and maintenance of pain responses induced by BmK I, the expression of Nav1.6 in DRG was found to be significantly increased at both mRNA and protein levels. The percentage of co-localization of Nav1.6 and Isolectin B4, a molecular marker of small diameter non-peptidergic DRG neurons, was increased at the maintenance phase of pain responses. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, were significantly alleviated after knockdown of Nav1.6. These data strongly suggest that Nav1.6 plays an indispensable role in the peripheral pain hypersensitivity induced by BmK I.