Comparative Evaluation of Perioperative Analgesic and Anaesthetic Efficacy in Supraperiosteal Infiltration of Tramadol Hydrochloride in patients with Symptomatic Irreversible Pulpitis – A Triple-blind randomized controlled trial.

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (Raja SN et al., 2020). Symptomatic irreversible pulpitis is generally considered to be the most difficult condition in dentistry with respect to pain control during and after treatment. Management of pain in symptomaticirreversible pulpitis is often an emergency condition that requires immediate treatment (Abbott et al., 2018). These teeth exhibit intermittent or spontaneous pain and are sensitive to thermal stimulus. Rapid exposure to dramatic temperature changes (especially to cold stimuli) will elicit heightened and prolonged episodes of pain even after the thermal stimulus has been removed (Berman LH, Hargreaves KM, 2020). Local anesthetics are used alone or in combination with adjuncts for pain control during the endodontic treatment of irreversible pulpitis. One of the most widely used methods to administer local anesthetics in maxillary teeth is local infiltration anesthesia.

Local anesthetics often fail to achieve adequate pain control in inflamed teeth, as it causes metabolic acidosis which lowers the tissue pH; greater fraction of the local anesthetic in the ionized form hindering diffusion into the axolemma (Tripathy KD, 2019). Nusstein et al. reported that only 68% patients had no pain following buccal infiltration injections in the treatment of maxillary teeth (Nusstein et al.,1998).

In maxillary molars, it has been shown that pain associated with treating the pulp in the palatal canal is the commonest reason for inadequate anaesthesia in teeth with irreversible pulpitis. The length of the roots, the presence of bone and maxillary sinus reduces the volume of the anaesthetic drug that reaches the targeted nerves (Ulusoy et al., 2013). Adjuvants or additives are often used with local anesthetics for its synergistic effect by prolonging the duration of sensory/motor block and limits the cumulative dose requirement of local anesthetics. A large array of adjuvants which include vasoconstrictors like adrenaline, alpha 2 adrenoreceptor antagonists like clonidine, dexmedetomidine, steroids like dexamethasone, benzodiazepine like midazolam, NMDA receptor antagonists like ketamine and magnesium sulphate, opioids like morphine, fentanyl, sufentanyl and tramadol have been used in medicine and surgery with varying degrees of success (Swain et al. 2017). Recent in vitro studies have shown that few opioids have anaesthetic effects (Jaffe R A et al., 1996). One of these opioids is tramadol hydrochloride, a centrally acting synthetic opioid analgesic indicated for moderate-severe pain management (Srivastava et. al., 2019).

Tramadol and its metabolite *O-*desmethyl-tramadol (M1) are agonists of the μ opioid receptor. Tramadol inhibits serotonin reuptake and inhibits nor-epinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improves the analgesic efficacy (Grond et al., 2004). The analgesic effect of tramadol is also mediated via indirect modulation of the central monoaminergic inhibitory pain pathways. (Power et al., 1991). Pang et al. reported the local anaesthetic effect of tramadol when injected intradermally and reduces propofol injection pain. Jendi et al evaluated the soft tissue anaesthesia produced by tramadol hydrochloride on gingival tissues in maxilla and concluded that tramadol has a local anaesthetic effect similar to lignocaine when injected as infiltration in oral soft tissues and can be used as an alternative to conventional local anaesthetic agents in minor oral surgical procedures.  In dentistry, tramadol was added to known anaesthetic agents and the combined effect was investigated. In one study, Pozos et al. used 4% articaine with 1: 100,000 epinephrine to provide mandibular anaesthesia in third molar extraction and also administered tramadol 50 mg/mL into the surgical site. Aksoy et al. evaluated the effects of submucosal tramadol on the success of inferior alveolar nerve blocks during root canal treatment of mandibular molars with symptomatic irreversible pulpitis. Al Haideri reported that tramadol alone or in combination with adrenaline can be used as a local anaesthetic for the extraction of upper molar tooth under supraperiosteal infiltration. Tramadol has been used as a sole local anaesthetic agent for dental extraction of upper teeth and is recommended as an alternative to conventional local anaesthetic agents (Haideri et al., 2013). However, an overall review of the literature revealed that there were no studies stated the efficacy of tramadol by itself as a sole local anaesthetic agent used for endodontic therapy, nor there were any reports comparing it with other local anaesthetic agents.

Hence the aim of this in vivo study is to comparatively evaluate the perioperative analgesic and anaesthetic efficacy of pure tramadol with lignocaine during the endodontic management of maxillary molars with symptomatic irreversible pulpitis.