| Recent years, according to change of environment and improvement in healthcare, tumor incidence has risen a lot as well as people can get a longer life expectation. It’s more common to come across patients with bone tumor or tumor spinal metastasis in clinic. Pain caused by tumor or surgical incision is always a headache problem. It will cause a lot of social problems, such as drug addiction and pain killer abuse. To find a traditional Chinese herb which can be used to instead usual pain killer will have big clinical significance.Transient Receptor Potential channels(TRP channels)are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. They can be activated by various of physical and chemical stimuli. TRP channels are involved in many physiological and pathological processes. TRPM8, AKA a cold sensor, is a newly found cold associated ion channel, which can be activated by cold(<25℃). The TRPM8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices(S1-S6). The first four, S1-S4, act as the voltage sensor and allow binding of channel agonists. S5 and S6 and a connecting loop, also part of the structure, make up the pore, a non-selective cation channel which consists of a highly conserved hydrophobic region.Cold or chemical stimulus can activate TRPM8 to release pain, whose mechanism is still uncertain.Borneol is a bicyclic organic compound and a terpene. One historical name for borneol is Borneo camphor which explains the name. Borneol was used as a pain releasing medicine in clinic for more than 2000 years since ancient China. However, the target of borneol in vivo is still unknown, same as its molecular biological mechanism. This research confirmed borneol’s analgesic effect and tried to explain the mechanism through many kinds of experimental methods. Our research firstly investigated the pain releasing mechanism of borneol through the level of animal, cells and molecule. We systematically studied the downstream mechanism of borneol’s pain releasing effect. We want to give a scientific evidence and a guide for people knowing more about the pain releasing mechanism of borneol through our study.Objective:Explain the mechanism of borneol’s analgesic effect.Methods:With clinic and animal experiments, we confirmed borneol’s analgesic effect on patients’ surgical incisions. We screened some of pain-associated ion channels by patch clamp and flexstation3.Using calcium-imaging to investigate borneol’s effect on cultured DRG neurons. Borneol associated locates were studied with some mutants. We also explored the connection between borneol and some of important analgesic mechanisms we already know by intrathecal injection of the selective antagonists.Results:Our research confirmed borneol’s effect as a pain killer by clinical and animal experiments. And this analgesic effect is dose-responsed. With calcium imaging, we found that borneol can activate TRPM8 mediated extracellular calcium influx in both HEK293 cells and DRG neurons. By patch clamp borneol also can induce an outwardly rectifying currents on HEK293 cells which expressed hTRPM8 channel gene in vitro. Comparison of borneol and menthol, we found that borneol and menthol had similar analgesic effect but borneol with little side effect. By intrathecal injection,borneol’s analgesic effect may have nothing to do with the activation of opioid receptor, GABAa receptor and glycine receptor. Metabotropic glutamate receptors may be involved in the mechanism.Conclusions:1. Borneol has obvious analgesic effect on surgical incision of spinal tumor. 2. Borneol’s analgesic effect is associated with the activation of TRPM8, which is not because of inhibiting TRPA1. 3. Borneol has better clinical value compared with menthol. 4. Metabotropic glutamate receptors may be involved in the mechanism. |
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