Issue Archive

Mediating roles of the vanilloid receptor TRPV1 in activation of rat primary afferent nociceptive neurons by formaldehyde

TIAN Li-Juan, DU Yi-Ru, XIAO Yong, LV Zhuo-Min, YU Yao-Qing, CUI Xiu-Yu, CHEN Jun

Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, China； Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi’an 710038, China

Abstract

The formalin test is a commonly used animal model of acute and tonic pain. However, the molecular targets of formaldehyde
(FA, the main ingredient of the formalin solution) on primary nociceptor cells remain controversial. In this report, the effects of FA on
electrophysiologically-identified primary nociceptor cells were evaluated in vitro and the roles of the vanilloid receptor TRPV1 in FAproduced
activation of primary nociceptors were also examined at both cellular and behavioral levels. Of 92 acutely dissociated dorsal
root ganglion (DRG) cells recorded by current patch-clamp technique, 34% were discharged by FA application with the mean onset
latencies of the first action potential (AP) being (367.34±32.96) s. All the FA-sensitive cells were identified as nociceptor cells by their
distinguishable features of AP including longer duration, existence of a hump (a shoulder or inflection) on the repolarizing phase, and
longer after-hyperpolarization of APs. Co-application of capsazepine (CPZ), a competitive antagonist of TRPV1 receptors, could
block FA-evoked firing with partial inhibition on the membrane depolarization of all cells tested. Of another 160 cells examined by
confocal calcium imaging, 32% were shown to respond to FA with an intracellular Ca2+ rise. Of 51 FA-sensitive cells, 67% were
suppressed by CPZ, suggesting partial involvement of TRPV1 in mediation of the FA-evoked intracellular Ca2+ rise. Under voltageclamp
mode, 41% of DRG cells were evoked to give rise to inward current with the remaining 59% being unchanged. In separate
experiments on the other 56 FA-sensitive cells, concentration-dependent increase in the FA-evoked current amplitude was demonstrated.
In comparison with controls, the FA-evoked inward current could be significantly suppressed by CPZ that was further enhanced by
HC-030031, a TRPA1 selective antagonist. Finally, local effects of CPZ were confirmed in the formalin test and it was shown that the
formalin-induced paw flinches were strongly suppressed by CPZ in phase 1 but with phase 2 being significantly suppressed only
during 25-55 min. It is therefore concluded that FA can directly activate a subpopulation of primary nociceptor cells and the FA-induced
AP discharges are likely to contribute mainly to phase 1, but not phase 2 of the formalin-induced nociception. The activation of primary
nociceptor cells by FA is likely to be mediated, at least in part, through TRPV1 and/or TRPA1 receptors.

Key words: Formalin test; nociceptor; TRPV1 receptor; dorsal root ganglion; patch clamp; calcium imaging

Received: 2009-09-23　　Accepted: 2009-09-28

Corresponding author: 陈军　　E-mail: junchen@fmmu.edu.cn

Citing This Article：

TIAN Li-Juan, DU Yi-Ru, XIAO Yong, LV Zhuo-Min, YU Yao-Qing, CUI Xiu-Yu, CHEN Jun. Mediating roles of the vanilloid receptor TRPV1 in activation of rat primary afferent nociceptive neurons by formaldehyde. Acta Physiol Sin 2009; 61 (5): 404-416 (in Chinese with English abstract).