text: As described in the article Nociception, nociception is the sensory nervous system's response to harmful stimuli, such as a toxic chemical applied to a tissue. In nociception, chemical stimulation of sensory nerve cells called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses and usually results in a subjective experience, or perception, of pain.
  Work by Pan et al. first showed that TET1 and TET3 proteins are normally present in the spinal cords of mice.  They used a pain inducing model of intra plantar injection of 5% formalin into the dorsal surface of the mouse hindpaw and measured time of licking of the hindpaw as a measure of induced pain.  Protein expression of TET1 and TET3 increased by 152% and 160%, respectively, by 2 hours after formalin injection.  Forced reduction of expression of TET1 or TET3 by spinal injection of Tet1-siRNA or Tet3-siRNA for three consecutive days before formalin injection alleviated the mouse perception of pain.  On the other hand, forced overexpression of TET1 or TET3 for 2 consecutive days significantly produced pain-like behavior as evidenced by a decrease in the mouse of the thermal pain threshold.  
  They further showed that the nociceptive pain effects occurred through TET mediated conversion of 5-methylcytosine to  5-hydroxymethylcytosine in the promoter of a microRNA designated miR-365-3p, thus increasing its expression.  This microRNA, in turn, ordinarily targets (decreases expression of) the messenger RNA of Kcnh2, that codes for a protein known as K11.1 or KCNH2. KCNH2 is the alpha subunit of a potassium ion channel in the central nervous system.  Forced decrease in expression of TET1 or TET3 through pre-injection of siRNA reversed the decrease of KCNH2 protein in formalin-treated mice.