Realize the "electronic" analgesic drugs!Can you say goodbye to painkillers?

Everyone must have experienced the experience of "somber desire". At this time, taking painkillers often become the choice of most people.

However, the side effects of existing neurological analgesic drugs have many restrictions on clinical applications. Therefore, how to develop effective analgesic drug substitutions has become a hot issue in the current development of new drugs.

Recently, Professor Xuan Zhaoqian of Dalian University of Science and Technology has cooperated with researchers from Northwestern University and Northwestern University and researchers in Oregon University to develop a biological absorbing flexible micro -flow control equipment, which is expected to be a substitute for analgesic drugs. And published the title of "Soft, BioresorBable Coolers for Reversible Conduction Block of Peripheral Nerves" on the famous international journal Science.

Pain is one of the most common clinical symptoms. Opioid (OPIOID) is very significant to alleviate moderate to severe pain, but large side effects (such as immune suppression, neuromatical disorders and depression, etc.) have limited its scope of use [1]. In addition, with great addiction and excessive death, opioids need a good alternative.

Among all opioid substitutes, some implanted electronic devices can hinder local nerve conduction through sound, light, electricity, thermal or mechanical, so as to achieve the role of alternative opioids. This alternative can effectively avoid the side effects of opioids and other neurological analgesic drugs, and have good application prospects.

Temperature is essential for biological activities of our body. The metabolism and electrical signal transmission in neural tissue show a certain temperature dependence. Local cooling of peripheral nerves can significantly reduce the conduction speed and strength of the nerve signal. The signal blocking of mammalian nerve impulses usually occurs below 15 ° C. Therefore, the use of local cooling methods to hinder nerve impulses to hinder good application prospects, and have the advantages of fast reverse and not addiction.

However, the method of local cooling blocking nerve impulses requires precise control of temperature and minimizes tissue damage caused by low temperature. In the past, the cooling nerve methods rely on external responsible facility conditions, and the application of cooling but nerve methods.

In this study, researchers use local cooling methods to cause reversible blockage to nerve, thereby achieving painkillers and avoid side effects of opioids and other analgesic drugs.

Fig.1 Soft, BioresorBable, Evaporative Microfluidic Cooler for An on-Demand Nerve Block.

This soft, absorbable peripheral nerve cooling micro -flow control device developed by researchers can perform reversible pain to patients within a limited time. This device consists of a microfluidic device and an electronic system, which can accurately measure the peripheral nerve temperature while cooling the nerves. At the same time, the elastic characteristics of the micro -flow control system combined with the external snake circuit provides a close mechanical and temperature interface for the nerves without suture. After the patience detection at 75 ° C, the material used in the device can be dissolved most of them within 20 days and completely eliminated after 50 days.

Fig.2 Evaporamed Microfluidic Cooling and Temperature Sensing System.

In this device, polymeric acid sibiol is mainly used as the main body of the microfluidic control system, and it has a good degradation rate and biocompatibility. Using liquid coolant otramiline (PFP) and dry N2 as the cooling core of the cooling, after entering the snake-shaped evaporation device by mixing the two, the whole fluorine pentane is used at room temperature (28-30 ° C) to cool the peripheral nerves. The room temperature will be -20 ° C within 2 minutes. At the same time, the magnesium line outside the snake -shaped device can be measured in real time to ensure the treatment effect of the nerve temperature as a temperature sensor to ensure the treatment effect and prevent low -temperature damage tissue.

Fig.3 in vitro Studies of Nerve-Cooling Effical.

To accurately measure the effect of nerve cooling. Researchers used hydrogels to conduct in vitro experiments at 37 ° C. The results show that the device can reduce the temperature from 37 ° C to 3 ° C within 5 minutes. After providing heat sources for the blood irrigation of the template nerve, the nerve temperature increases from 3.5 ° C to 5.5 ° C. In a continuous cooling operation for 21 consecutive days, the temperature standard difference between the device is 0.6 ° C, indicating that the device has better cooling stability.

Fig.4 cooling localization.

In addition, researchers also use structural mechanics, heat transfer analysis and other methods to confirm that the device can locate the cooling effect to the predetermined position without the insulation layer, which can achieve accurate cooling effects.

Fig.5 cooling-induced nerve block and analgesia.

Finally, the researchers used neurological pain mice models to verify the effect. The results show that the device can be reduced from 31 ° C to 5 ° C within 8 minutes, effectively inhibiting the occurrence of pain, and can maintain normal nerve activity after temperature recovery. In addition, the settings are set in the animal's body for 6 months to maintain good nerve contact capabilities. In summary, the use of the device requires the following three conditions:

1) The anatomical area of ​​abnormal nerve signals is clear;

2) The nerves carrying abnormal nerve signals have been isolated;

3) Analgesic drugs need to be used after clinical surgery.

The three clinical applications, including amputation, nerve transplantation, and spinal decompression surgery, are in line with the above three conditions, so the device can be applied directly. During the use of the device, first implant the cooler absorbed by the surrounding of the target nerve, but the pain signals generated by the nerve impulses can be reverted through cooling peripheral nerves. The device uses water -soluble material, which will naturally dissolve naturally during wound healing, so that there is no additional surgical operation. This device has the characteristics of biological absorption sensors, which can be used to monitor and accelerate wound healing, and has good development prospects.

From this study, we can see that the advantages of electronic medical equipment in neuropharmaceutical alternatives have provided new ideas for future drug development.

references:

1.rosoff, D. B. (2020). Prescripting opioid used and risk for major depression disorder and anxiety and stress-related disorders. Jama psychiatry.

2.Reeder et al. "Soft, bioresorBable Coolers for Reversible Conduction Block of Peripheral Nerves." Science 377.6601 (2022): 109-115.

- END -