Green tea has many pharmacological actions mainly attributed to catechins. Studies have demonstrated an antinociceptive effect of green tea extract on inflammatory and neuropathic pain [1
]. (−)-Epigallocatechin-3-gallate (EGCG) is one of the major catechins of green tea leaves and it has been shown to exhibit analgesic efficacy. It has been suggested that EGCG produces an antiallodynic effect against neuropathic pain by blocking the increase in nitric oxide synthase (NOS) expression in the spinal cord and thus inhibiting the pronociceptive effects of nitric oxide (NO) [3
]. Moreover, EGCG dramatically improved pain behaviors in a rat chronic constriction injury model of neuropathic pain [4
]. (−)-Gallocatechin-3-gallate (GCG) is produced following the epimerization of EGCG during the heating procedure (). Therefore, the stability of GCG is much better than that of EGCG. Studies have shown that GCG has the most prolonged hypotensive effect in rabbits among the catechins [5
], and the inhibitory effect of GCG on cholesterol absorption was more effective than that of EGCG [6
]. However, GCG has received relatively little attention because its content in green tea is much less than EGCG. Recently, instead of EGCG, GCG was found to be the predominant catechin in cocoa tea, which is a naturally decaffeinated tea plant growing in southern China [7
]. It is therefore necessary to investigate the analgesic efficacy of GCG.
Chemical structures of (−)-Epigallocatechin-3-gallate (EGCG) (A) and (−)-Gallocatechin-3-gallate (GCG) (B).
Voltage-gated sodium channels (Nav), which produce the inward membrane current necessary to produce regenerative action potentials in neurons and muscle cells, have emerged as important targets in the study of the molecular pathophysiology of pain and in the search for new pain therapies [8
]. Nociceptive neurons within dorsal root ganglia (DRG) express multiple Na+
channel subtypes that can be separated into two groups based on their susceptibility to tetrodotoxin (TTX) [9
]. Small-diameter (<25 μm) rat DRG neurons express a combination of fast tetrodotoxin-sensitive (TTX-S) and slow tetrodotoxin-resistant (TTX-R) Na+
currents while large-diameter (>30 μm) neurons predominately express fast tetrodotoxin-sensitive Na+
]. Tetrodotoxin-resistant Na+
currents show distinctive biophysical properties, such as persistent and slowly inactivating currents. The persistent current has been attributed to Nav1.9, and the slowly inactivating current to Nav1.8. By transmitting the majority of nociceptive signals to the spinal cord, small to medium-sized DRG neurons play an important role in pain sensory detection.
Previous studies have found that EGCG potently inhibited tetrodotoxin-sensitive and tetrodotoxin-resistant Na+
currents in rat DRG neurons [10
], and Na+
currents in rat hippocampal neurons in a concentration-dependent manner [11
]. We therefore sought to investigate whether GCG could suppress Na+
currents passing through nociceptive-related tetrodotoxin-resistant Na+
channels in rat DRG neurons, and if so, whether the inhibition was frequency-dependent. The results suggest that GCG may reduce pain peripherally through inhibition of tetrodotoxin-resistant Na+
currents in nociceptive sensory neurons.