There are three types of primary peripheral afferents: Ab fibers, Ad fibers, and C fibers. Ab fibers are the quickest conducting fibers due to their myelinated quality. Ad fibers are slightly slower, comprising thinner myelinated axons. The slowest conducting fibers are the C fibers consisting of the thinnest and unmyelinated fibers [2].

Trigeminal nerve mostly innervates the orofacial region, and its primary afferent cell bodies are found within the trigeminal ganglion which consists mostly of Ad fibers and C fibers [3]. The Ab fibers of the trigeminal region respond to pressure and light touch, while pain acts as a stimulus to the less conducting Ad fibers and C fibers, which are jointly termed nociceptors, the excitation of which causes considerable release of sP, which activates neurokinin-1 receptors and thereby modulates sensitivity to pain [4]. These nociceptors can be further classified into mechano-nociceptors, thermo-nociceptors, and chemo-nociceptors. Thermo-nociceptors contain vanilloid receptor 1-like receptors that contribute to the pain due to extreme temperatures [5]. Mechano-nociceptors, which are sensitive to mechanical stimuli, are located in the root pulp and are lined with epithelial Na⁺ channels that contribute to sharp pain produced by liquid motion in the dentinal tubules [6]. Chemo-nociceptors are sensitive to chemicals.

The modulation of these nociceptors is either mechanical or chemical. Canine studies have shown that the threshold for mechano-nociception can increase sensitization because it may be lowered by periodontal inflammation [7]. It is possible that this is due to the hydrodynamic mechanism (which activates the nociceptors by increasing pressure on the pulp [8]) of inflammation in the noncompliant environment in the dentine-encased pulp. In addition, there is substantial peripheral and central modulation due to the various neuropeptides released following tissue damage, and it is localized within the trigeminal ganglia. Peptides such as sP and calcitonin-related peptide are crucial in sensitizing the nociceptors: this leads to allodynia, the pain to innocuous stimuli, and hyperalgesia, increased sensitivity to painful stimuli [9].

The primary afferent neurons terminate in the trigeminal spinal tract nucleus in the brain stem. The trigeminal spinal tract nucleus is made up of three subnuclei: the subnucleus oralis, subnucleus interpolaris, and subnucleus caudalis. The subnucleus caudalis is structurally comparable to the spinal dorsal horn and hence often called the trigeminal dorsal horn [10]. This subnucleus functions as the main brain stem relay and is a critical central structure for the modulation of nociception. The subnucleus oralis and subnucleus interpolaris both receive a versatile input from all three types of fibers, particularly from the quickly conducting Ab fibers. The central neurons found within these subnuclei are further subdivided into nociceptive specific neurons. This consists of either Ad fibers and C fibers that respond only to noxious stimuli or all the three fiber types that respond to both noxious and innocuous stimuli [11]. Deep pain is attributed to the convergence of various types of receptors into a central nociceptive neuron. The intricacy of this convergence results in the misreading of the original sensation, leading to allodynia or hyperalgesia [12]. In addition, various other studies have also found that the transition zone between the subnuclei caudalis and the subnuclei interpolaris also contributes to the central processing of deep orofacial nociception [13].

From the brain stem, the orofacial impulses are conducted through the thalamus to the cortex. In the thalamus, mainly the posterior nucleus, ventral posterior nucleus, and intralaminar nucleus, nociceptive specific neurons and wide dynamic range neurons are located. The ventral posterior nucleus is involved in localization of pain to a region, and the intralaminar nucleus is responsible for the affective and motivational dimension to pain and identification of stimuli as pain is caused by the posterior nucleus. In effect, the lateral thalamus projects to the somatosensory cerebral cortex to narrow down and identify the location of the pain, and the medial thalamus projects to neighboring areas such as the hypothalamus and the cingulated gyrus in order to associate the pain with their relevant emotions [14].