Chronic pelvic pain syndrome is a condition with strong impact on quality of life. Etiology is still unknown, especially for central sensitization cases. Some researchers published the result of their trials, which demonstrated significant decrease of the pain threshold in patients with CPPS [1]. Hence, normalization of pain threshold can improve the symptoms. There are many animal experiments, confirmed increasing of the pain threshold with melatonin administration [2]. Problem is a short duration of melatonin's action. We've developed hydrogel-based slow-release melatonin with a long releasing profile. We decided to conduct the animal study for estimation of releasing profile of this hydrogel in vivo.

30 rats participated in experiment. Average weigh was 257 + 13 g. 20 rats were included to melatonin group, 10 rats have been included into control group. Animals of experimental group received per os  the 0.25 ml hydrogel, made of hyaluronic acid and pectin contains 2.5 mg of melatonin. One-hour later pain threshold has been measured with hot water tail flick test. Rat was immobilized and her tail has been put into the water with 52 C temperature. Time of the latency was measured. Test was repeated every hour 8 times. Animals of the control group received 0.25 ml of hydrogel without melatonin (placebo). Hot water tail flick test was performed with same method.

Average latency time in placebo group was 7.6 + 0.9 sec. Animals in melatonin group demonstrated the results, listed below (latency time):
1st hour: 8.1 + 0.8 sec (non-significant difference)
2nd hour: 12.3 + 1.0 sec (significant difference)
3rd hour: 16.7 + 1.2 sec (significant difference)
4th hour: 15.4 + 1.2 sec (significant difference)
5th hour: 14.2 + 1.1 sec (significant difference)
6th hour: 12.1 + 1.0 sec (significant difference)
7th hour: 9.6 + 0.9 sec (non-significant)
8th hour: 8.2 + 1.0 sec (non-significant)

Significant difference of latency time between melatonin group and placebo group was noticed since 2nd till 6th hours. Melatonin can increase pain threshold, but hydrogel – based slow-release melatonin can significantly increase pain threshold during six hours.

Hydrogel – based slow-release melatonin is a promising solution for CPPS treatment, especially in cases with pain in night time (IC/BPS for example). Further trials needed.

Giamberardino MA, Tana C, Costantini R. Pain thresholds in women with chronic pelvic pain. Curr Opin Obstet Gynecol. 2014 Aug;26(4):253-9. doi: 10.1097/GCO.0000000000000083. PMID: 24921647.
Xie S, Fan W, He H, Huang F. Role of Melatonin in the Regulation of Pain. J Pain Res. 2020 Feb 7;13:331-343. doi: 10.2147/JPR.S228577. PMID: 32104055; PMCID: PMC7012243.