Effect of Menstrual Phase on the Anesthetic Efficacy of Inferior Alveolar Nerve Block in Patients With Symptomatic Irreversible Pulpitis in Mandibular Molars

Introduction Pain management is fundamental to the success of dental procedures, particularly in endodontics, where patients often present with severe preoperative pain due to irreversible pulpitis. The inferior alveolar nerve block (IANB) is the most frequently employed anesthetic technique for mandibular molars, yet its reliability in inflamed pulpal conditions remains questionable. Numerous studies have documented variable efficacy, with failure rates ranging between 30% and 80%, despite correct technique and the use of appropriate anesthetic agents (1). This unpredictability poses a significant challenge, often necessitating supplemental injections such as intraligamentary, intraosseous, or intrapulpal techniques to achieve adequate pain control.

Traditionally, the reasons for IANB failure in irreversible pulpitis have been attributed to local and central mechanisms. Locally, inflammation-induced acidosis decreases the proportion of anesthetic molecules in their non-ionized, membrane-penetrating form, thereby reducing nerve blockade efficiency (2). Inflammatory mediators, including prostaglandins and bradykinin, also sensitize nociceptors and increase expression of tetrodotoxin-resistant sodium channels, which are inherently less sensitive to lidocaine and other amide anesthetics. At the central level, hyperalgesia and central sensitization amplify nociceptive transmission, contributing to anesthetic resistance (1). Patient-related variables, such as anxiety and fear, further modulate pain perception and anesthetic outcome.

However, even after controlling for these factors, considerable inter-individual variability remains unexplained, suggesting a systemic or constitutional influence. Increasing attention has therefore been directed toward genetic, hormonal, and gender-related factors as potential modulators of anesthetic efficacy.

A large body of literature has established sex-based differences in pain perception. Women consistently report a higher prevalence of pain conditions such as migraine, temporomandibular disorders, and fibromyalgia compared to men (3). Experimental models demonstrate that women often have lower pain thresholds, reduced tolerance to noxious stimuli, and enhanced temporal summation of pain (4). These findings suggest an inherent biological variability in nociceptive processing, which extends to the clinical response to local anesthesia. Indeed, several dental anesthesia studies have observed that women require supplemental injections more frequently than men for comparable procedures (Aggarwal et al., 2009).The underlying mechanism for these sex differences is multifactorial. While psychological and cultural factors may influence pain reporting, biological variables-particularly the role of sex hormones-are now considered central.

The menstrual cycle is characterized by cyclical fluctuations in estrogen and progesterone. These hormones exert significant effects on nociceptive transmission and pain perception at peripheral, spinal, and supraspinal levels.Estrogen has dual, context-dependent effects. It can enhance excitability of nociceptive neurons by upregulating sodium channels and NMDA receptors, thereby facilitating pain (4). Conversely, estrogen also promotes endogenous opioid activity, especially via μ-opioid receptors in the central nervous system, which can increase pain inhibition (5).Progesterone is thought to lower pain thresholds by modulating GABAergic and sodium channel activity. High-progesterone phases, such as the luteal and premenstrual phases, have been associated with increased sensitivity to painful stimuli (4, 5).