ABSTRACT
Background DPP-4 inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day 1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to receive other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) was monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated modest analgesic activity compared to baseline and placebo. Its role in painful diabetic conditions may be further explored.
ABSTRACT
The vanilloid receptor TRPV1 has been suggested to play an important role in thermal nociception and inflammatory hyperalgesia. In our previous study, we examined the expression of TRPV1 and colocalization of TRPV1 with substance P (SP) and calcitonin gene related peptide (CGRP) through fluorescence immunocytochemistry. Here, we investigated ultrastructural characteristics of TRPV1 immunoreactive fibers in the human tooth pulp through preembedding immunocytochemistry. TRPV1 immunoreactivity was present in the unmyelinated nerve fibers in the tooth pulp. There were two types of TRPV1 IR nerve fibers identified in the human tooth pulp: one containing clear round vesicles and many dense-cored vesicles, the other containing clear round vesicles and few dense-cored vesicles. TRPV1 immunoreactive fibers were constant in diameter without swellings along the length. Boutons en passant and boutons terminaux usually observed in the CNS were not observed in the TRPV1 immunoreactive fibers. Many vesicles were accumulated in the TRPV1 immunoreactive fibers, however synaptic structure was not found. It is known that dense-cored vesicles contain neuropeptides such as SP and CGRP and clear round vesicles contain neurotransmitter such as glutamate. Taken together, our results suggest that TRPV1 immunoreactive fibers showing distinct ultrastructructural features may be involved in inflammatory hyperalgesia and thermal nociception in the tooth pulp.