Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp

Abstract

Introduction The unique innervation and anatomical features of the dental pulp contribute to the remarkable finding that any physical stimulation of pulpal tissue is painful. Further, when pathological processes, such as caries, affect teeth, and produce inflammation of the pulp, the pain experienced can be quite intense and debilitating. To better understand these underlying neurobiological mechanisms, and identify novel analgesic targets for pulpally derived pain, we have developed a powerful ex vivo model using human tooth slices. Methods Non-carious, freshly-extracted teeth were collected and sectioned longitudinally into 1mm thick slices containing both dental pulp and the surrounding mineralized tissues. Tooth slices from 36 patients were exposed to 60 uM capsaicin to stimulate the release of calcitonin gene-related peptide (CGRP) from nerve terminals in the pulp. Patient factors were analyzed for their affects on capsaicin-stimulated CGRP release using a mixed model ANOVA. Results Approximately 1/3 of the variability observed in capsaicin-evoked CGRP release was attributable to differences between individuals. In terms of individual factors, there was no effect of anesthesia type, sex or age on capsaicin-stimulated CGRP release. Using a within-subject study design, a significant effect of capsaicin on CGRP release was observed. Conclusions Capsaicin-stimulated CGRP release from dental pulp is highly variable between individuals. A within-subject study design improves the variability and maximizes the potential of this powerful translational model to test the efficacy of novel pharmacotherapeutic agents on human peripheral nociceptors.

Disclosing the physiology of pulp tissue for vital pulp therapy

“…There are several TRP receptors in odontoblasts, including the transient receptor potential cation channel subfamily V channels (TRPV) (Burns et al 2016). thermal, mechanical and chemical) can activate dentinogenesis.…”

“…Pro-inflammatory vasodilator that is released after activation of transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurons (Brain et al 1985, Burns et al 2016. Calcitonin receptor-like receptor (CRLR) is expressed in pulp during a clinical inflammatory process (Caviedes-Bucheli et al 2005.…”

“…To respond to these stimuli, odontoblasts express members of the transient receptor potential (TRP) family. There are several TRP receptors in odontoblasts, including the transient receptor potential cation channel subfamily V channels (TRPV) (Burns et al 2016). TRPVs are able to respond to a variety of stimuli.…”

Dental nerves: a neglected mediator of pulpitis

“…Thus, it seems that thermal, chemical and electric stimuli of sufficient intensity to dental nerves would lead to an increased secretion of functional molecules. However, the release of neuropeptides is highly variable between different individuals even under the same stimulating conditions (Burns et al 2016). It is worth noting that this increased release might not be the only cause of high extracellular levels of neuropeptides in pulpitis (Bowles et al 2003a,b).…”

TRPV1-Like Immunoreactivity in the Human Locus K, a Distinct Subregion of the Cuneate Nucleus

“…The aberrant activation of TRPV1 has been implicated in different neuropathological conditions including inflammation [ 38 , 39 , 40 , 41 , 42 , 43 ], neuropathic pain [ 26 , 27 , 31 , 43 ], visceral pain [ 40 , 41 , 43 , 44 , 45 ], nerve injury [ 43 , 46 , 47 ] and migraine [ 33 ]. In humans, the local injection of capsaicin has been shown to cause sensitization of the cutaneous afferents [ 48 , 49 , 50 ], release of CGRP from peripheral nerve endings [ 11 , 51 , 52 ] and pain in the deep somatic tissues [ 53 , 54 , 55 , 56 ].…”