Table 1.

Summary of evidence of serotonergic neuromodulation of TRPV1 nociceptors

Type Sensory Neurons	Methodology	Reported Findings	Citation
rat DRG neurons	ISH/IHC	13% DRG neurons coexpress 5HT3 mRNA and TRPV1	Zeitz et al., 2002
rat DRG neurons	microdialysis	5HT2A/2C agonist induces a 4-fold increase in capsaicin- evoked substance P release in the dorsal horn; 8-fold increase during inflammation; attenuated with 5HT2A antagonist	Bertelsen et al., 2003
rat colonic sensory neurons	whole-cell patch clamp	1 μM 5HT lowers thermal thresholds and enhances capsaicin-evoked currents via 5HT2 and 4 receptors	Sugiura et al., 2004
rat cutaneous nociceptors	spontaneous pain behaviors	50 nmol 5HT prolongs capsaicin-evoked flinching and licking/biting of the hindpaw	Sawynok et al., 2006
cultured rat TG neurons	whole-cell patch clamp	10 μM 5HT exposure upregulates the amplitude of capsaicin-evoked currents	Simonetti et al., 2006
cultured rat DRG neurons	whole-cell patch clamp and calcium imaging	10 μM 5HT potentiates capsaicin-evoked current and calcium influx via 5HT2A and 7 receptors; more prominent in DRG from inflamed rats	Ohta et al., 2006
rat DRG neurons	IHC	5HT2A receptors coexpress with TRPV1 in DRG	Van Steenwinckel et al., 2009
rat colon sensory neurons	whole-cell patch clamp and visceral pain behaviors	Endogenous 5HT depletion augments capsaicin- evoked visceral hypersensitivity and capsaicin- evoked currents	Qin et al., 2010
cultured rat TG neurons	calcium imaging and peptide release	5HT enhances capsaicin-evoked calcium influx and CGRP release via 5HT1B/1D, 2A and 3A receptors which colocalize with TRPV1	Loyd et al., 2011
rat cutaneous nociceptors	thermal pain behavior	Peripheral 5HT prolongs capsaicin-evoked thermal hypersensitivity via 5HT1B/1D, 2A and 3A receptors	Loyd et al., Neurosci 2012
human dental pulp nociceptors	in vitro superfusion	5HT enhances capsaicin-evoked CGRP release in dental pulp from female but not male teeth	Loyd et al., Pain 2012