**5.5 Tetrodoxin resistant channels (TTXr)**

The Tetrodoxin resistant channels (TTXr) family of sodium channels have been demonstrated to be resistant to the effects of local anesthesia. Anesthetic failures in a hot tooth are caused by increased expression of sodium channels in the pulp. The TTXr channels are resistant to lidocaine, resulting in insufficient anesthetic [18]. TTXr channels are expressed on nociceptors, and their activation with Prostaglandin E2 is relatively resistant to lidocaine. Because they are less susceptible to lidocaine, sodium channels that are resistant to TTX. As the concentration of lidocaine rises, the sodium channels get blocked [19].

## **5.6 Altered membrane excitability of peripheral nociceptors**

Inflamed tissue nerves have a lower excitability threshold and an altered resting potential. Lower excitability thresholds are responsible for impulse transmission [20].
