Immunohistochemical Evidence for ATP Receptors in Human Dental Pulp

Abstract

Evidence is accumulating which supports a role for ATP in the initiation of pain by acting on P2X receptors, in particular P2X3, expressed on nociceptive afferent nerve terminals. To investigate whether this receptor plays a role in dental pain, we studied the presence and distribution of P2X3 receptors in human dental pulp, and their co-localization with other neural markers. Pulps were removed from extracted third molars and immunohistochemically stained with an antibody against P2X3 receptors. P2X3 immunoreactive (-ir) nerve fibers were detected in the main body of the pulp, in the sub-odontoblastic plexus of Raschkow, and within the odontoblastic area. Co-localization of the P2X3-ir neurons with neurofilament protein (NF) showed that the majority of the fibers were positive for both NF and P2X3. Double labeling with isolectin B4 (IB4) showed that all P2X3-ir neurons also bind IB4. We conclude that P2X3 receptors are present on both myelinated and unmyelinated nerve fibers in human dental pulp and may play a role in dental pain mechanisms.

Analysis of the distribution of binding sites for the plant lectin Bandeiraea simplicifolia I‐isolectin B4 on primary sensory neurones in seven mammalian species

“…Furthermore, recent studies have reported BSI-B 4 binding sites on human primary sensory neurones collected either post-mortem or from patients undergoing surgery (Yiangou et al, 2000;Alavi et al, 2001). Collectively, these findings suggest that the glycoconjugate to which BSI-B 4 binds has a ubiquitous distribution in mammals, and appears to be expressed in a subpopulation of small-diameter primary sensory neurones.…”

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

“…These in vitro data imply that P2X 2/3 receptors may be located presynaptically on the central terminals of primary afferent neurons. In the case of trigeminal primary afferents with their central terminals in the medullary dorsal horn, this would include P2X receptorexpressing nerve terminals innervating the rat and human tooth pulp Alavi et al, 2001;Renton et al, 2003) rat TMJ Shinoda et al, 2005) masseter muscle (Ambalavanar et al, 2005) and dura (present study).Other pharmacological studies indicate that P2X 2/3 and P2X 3 receptors play important roles. Nociceptive behaviour evoked by either peripheral inflammation in the hind-limb or intrathecal application of α,β-meATP can be inhibited by the P2X receptor antagonist TNP-ATP (Tsuda et al, 1999) or the highly selective P2X 2/3 /P2X 3 receptor antagonist A-317491 (McGaraughty et al, 2003), and P2X 3 receptor gene ablation or antisense oligonucleotides targeting the P2X 3 receptor gene result in significant antinociception (Honore et al, 2002;Cockayne et al, 2005).…”

“…These in vitro data imply that P2X 2/3 receptors may be located presynaptically on the central terminals of primary afferent neurons. In the case of trigeminal primary afferents with their central terminals in the medullary dorsal horn, this would include P2X receptorexpressing nerve terminals innervating the rat and human tooth pulp Alavi et al, 2001;Renton et al, 2003) rat TMJ Shinoda et al, 2005) masseter muscle (Ambalavanar et al, 2005) and dura (present study).…”

“…These neurons supply tissues that are predominantly innervated by small-diameter nociceptive afferents, some of which have unique features related to pain (see Bereiter et al, 2000;Sessle, 2000;. These P2X receptor-expressing neurons include those innervating the rat and human tooth pulp Alavi et al, 2001;Renton et al, 2003), rat temporomandibular joint (TMJ) Shinoda et al, 2005) and masseter muscle (Ambalavanar et al, 2005). Most of these studies reported P2X 3 receptor expression, and some noted increased P2X 3 receptor expression after inflammation or nerve injury (Eriksson et al, 1998;Ambalavanar et al, 2005;Shinoda et al, 2005).…”

Expression of Ecto-ATPase NTPDase2 in Human Dental Pulp

“…ATP depolarizes the membrane potential and excites sensory neurons by activating ionotropic purinergic (P2X) receptors (Chen et al, 1995;Hamilton, 2002;Wirkner et al, 2007). Ionotropic P2X3 receptors have been detected in trigeminal ganglia neurons and in dental pulp nerve fibers projecting into the odontoblast layer and the dentin tubules (Alavi et al, 2001;Jiang and Gu, 2002;Renton et al, 2003). These observations suggest that ATP signaling might be involved in the process of dental nociception.…”