**Abstract**

Achieving anesthesia in a hot tooth or tooth with inflamed pulp is challenging, especially during endodontic treatment. In the presence of symptomatic irreversible pulpitis, mainly in mandibular teeth, pose even more challenge to attain profound anesthesia. Tetradoxin resistant channel is a class of sodium channel that is found to be increased in such condition and is found to resist local anesthesia. The pH also determines the success of local anesthesia. In inflammatory conditions, the surrounding area's pH, which eventually decreases the amount of base form of local anesthetic penetration into the nerve membrane, thereby causing anesthetic failure. In such conditions, the excitability threshold is reduced, leading to failure in achieving anesthesia. This chapter highlights and discusses the cause of anesthetic failure and its management in obtaining profound anesthesia during endodontic treatment.

**Keywords:** Local Anesthesia, Endodontic Treatment, Pain, Irreversible Pulpitis Pulpal Inflammation

## **1. Introduction**

Pain is an unpleasant sensation that can range from slight discomfort to excruciating agony and can be linked to actual or potential tissue damage [1]. It is a multimodal and biopsychosocial event with an individual objective and subjective occurrences, resulting in significantly diverse perceptions of pain between the individuals. One of the most common reasons for a patient to visit an endodontist is dental pain. Managing dental pain and anxiety during and after treatment is still a difficult task, which depends on the clinician's skill and knowledge [2].

### **2. Pulpal inflammation**

In symptomatic pulp tissue diagnosed with irreversible pulpitis, extracellular levels of Substance P are elevated. When comparing pulp tissue diagnosed with irreversible pulpitis to clinically normal pulp tissue, an 8-fold rise in Substance P was found [3]. As a result, irreversible pulpitis is linked to high peptidergic system activation. It is generally known that root canal preparation causes inflammation in the periapical tissues, explaining why root canal therapy causes post-treatment pain (such as symptomatic apical periodontitis). SP is released in the periodontal

ligaments as a result of varied canal preparation approaches, which was found to be quite interesting. However, the amount of released SP differs among procedures. Inflammation in the periapical tissues could be triggered by an elevation in SP [4]. This might thus be considered a key mediator of neurogenic inflammation and related hyperalgesia, and hence a prospective target for therapeutics targeted at regulating pain and minimizing the harmful effects of tissue injury [5].

When a carious lesion gets close to the pulp, the pulp's inflammatory alterations get worse. An acute exacerbation of chronic inflammation occurs at this stage, with an influx of neutrophils and the release of inflammatory mediators (prostaglandins and interleukins), proinflammatory neuropeptides and mediators (substance P, Bradykinin, and calcitonin gene related peptide) [6]. These mediators can increase pain perception and neuronal excitability by stimulating peripheral nociceptors within the pulp of the affected tooth. This causes moderate-to-severe discomfort. Conventional procedures may not provide sufficient anesthesia. As a result, endodontists must achieve profound anesthesia in order to alleviate the pain [7].
