A big concern in medicine today is the problem of pain relief, especially the issues toxicity, addiction and low efficacy. Choices available to patients are limited and the usual mainstays for pain have not stood up well to the scrutiny of evidence-based medicine. We need new tools.
You may be aware of the value of acupuncture for pain control, this has become so well-established now that some hospital Emergency Rooms offer the treatment and the US Army now employs battlefield acupuncturists to treat pain from injuries. But, whilst acupuncture has emerged as a promising choice, it does not enjoy the convenience of oral medications.
Current pain Medications
Paracetemol (acetaminophen) turns out to be less effective and more risky that everyone imagined. Research shows that it provides adequate relief for around a quarter of people who take it. On top of that, it has a narrow therapeutic dose range – if you don’t take quite enough it does nothing and taking a bit too much risks liver damage. The fact that many over-the-counter products contain this drug makes it too easy to accidentally overdose and worrying numbers of people end up in hospital (or worse) this way.
Aspirin and related anti-inflammatories drugs such as Brufen (Ibuprofen, Nurofen), Naprosyn (Naproxen) and Voltarol have a mild to moderate benefit but put you at significant risk of gastro-intestinal bleeding. Thousands are hospitalised every year in the UK for this complication and around 1 in 8 of those hospitalised die.
Short on options, doctors have turned to meds that were licensed for other indications, but these are not great either. Epilepsy drugs, such as Gabapentin, have been tried on the basis that they make nerves less sensitive but the evidence of overall benefit is questionable, with manufacturers Pfizer fined for fraud and a researcher who fabricated research jailed. Whistle-blower Mark Mosely MD writes “we have a professional obligation to stop prescribing these drugs”[1]
Research showed that people who are depressed are more sensitive to pain led to the trialling of the old-fashioned MAO-inhibitor antidepressants as well as the SSRI antidepressants such as Prozac but these too have drawbacks.
Opiates such as morphine and codeine are valuable for severe acute pain and for those needing terminal care but these drugs are unsuitable for longer term use as they require ever increasing doses to stay effective and they bring addiction problems. Around 25 years ago a new class of opiate drugs appeared, such as Fentanyl and Oxycontin. Some were a hundred times more potent than morphine yet manufacturers persuaded doctors to prescribe them for all types of pain, falsely claiming that they did not cause dependency and were suitable for long term use. In the US these drugs now kill around 50,000 annually and have brought problems that are costing the government almost $80Bn per year to tackle.
Oxycontin’s manufacturers were recently fined $8.9Bn for corrupt practices in marketing this drug. In October 2020 New Scientist reported that they were found guilty of “violating anti-kickback laws [i.e. bribing doctors], conspiracy to defraud the US and facilitating the dispensing of medication without a legitimate purpose”. The company declared bankruptcy.
The Search for New Options
The quest is to find better pain medications with pharmacologists searching high and low for compounds that fit the bill. Candidate drugs have included exotic insect, toad and snake venom but, although powerful, these can be impractical or risky. So, for the last few decades, science has turned to Chinese herbal medicine for help.
It is fair to say that Chinese medicine has emerged as the most viable complement to modern medicine. Although by no means perfect or fully proven, it does have a sophistication that comes from its long history of use on billions of people by educated physicians, an extensive documented written tradition and is backed up by extensive modern research. A literature search for any of the 250 or so commonly herbs used in Chinese medicine will turn up hundreds of research papers on each one.
Pharmacologists have studied various herbs traditionally use for pain and explored the way they work. Chuan xiong (Ligusticum tuber) has been found to inhibit pro-inflammatory cytokines and to calm neuropathic pain pathways. Chuan wu (Aconitum tuber) inhibits spinal sensory pain pathways (C-fibres) and stimulates spinal dynorphin production.
The front runner in this search for the ideal analgesic is the herb Yanhusuo (Corydalis yanhusuo), a tuber that has been used to treat pain since it was recorded in a medical text called the BenCao ShiYi authored by Chen Cang-qi in 720 AD. Today a search on the Pubmed research database gets around 715 hits for Corydalis supporting the idea that this may be worthwhile choice as an analgesic. The picture that emerges when we investigate the pharmacology of most substances in the Chinese materia medica gets intriguing and contrasts with licensed chemical medicines. Pharmaceutical drugs are single chemical entities intended to hit single target in the body – when they mess with other aspects of the body these are seen as risks and side effects to be factored in to the benefits-downsides analysis. One thing that makes Chinese herbal medicine interesting is that its treatments contain many biologically active substances that affect multiple aspects of our biochemistry and that these are often found to provide collateral benefits rather than harms. Polypharmacy is a dirty word in biomedicine but may be seen as one of the strengths of Chinese medicine. And this is exactly what we find when we look into the pharmacology of Yanhusuo. The work so far has identified around 100 active components, some able to relieve pain and others with those collateral benefits. Here is a brief overview.
Pain
Amongst Chinese doctors Corydalis is traditionally seen as having a morphine-like ability to relieve pain and a clinical trial has helped confirm its value[2].
Yes, it does contain some components with mild opiate activity but the pharmacology now tells us that this is not the main explanation for its analgesic properties. Instead, the analgesia it provides is largely due to DHCB (dehydrocorybulbine) alkaloids that affect dopamine D2 and THP (tetrahydropalmatine) receptors that are involved in conveying pain signals to the brain. It also has anti-cholinesterase activity which provides another part of its pain relief effect[3]. Unlike opiate analgesics the evidence indicates that subjects do not develop dependency or tolerance[4], it seems to work in a way that does not require ever-increasing doses to work and so it is believed to be suitable for chronic pain management.
Historically, China’s doctors found the pain-relieving action of Yanhusuo is stronger if it is stir-fried with vinegar, this and indeed the research suggests a 20-30% increase in its power when prepared this way. The tradition also reports that it works best when an expert physician combines herbs strategically into a prescription that is tailored to the individual. For example, its effect on menstrual pain, for example, is enhanced when Corydalis is paired with the fruit TCM calls Chuan Lian Zi (Melia toosendan).
Co-lateral benefits
And this brings us to that intriguing aspect of Chinese medicine mentioned before - the way that their side effects tend to be beneficial to health rather than harmful. An effect that has long been used deliberately and strategically by well trained TCM physicians.
Here are some of the beneficial effects of Yanhusuo.
Anti-inflammatory - The pharmacology studies have found Yanhusuo to have anti-inflammatory effects [5,6]. This is a useful side effect because so often pain and inflammation happen together.
Hepatoprotective - Virtually all medicines are broken down in the body by the liver and so their hepatotoxicity often brings risks and limits what can be done clinically. It is hepatotoxicity of Paracetemol that leads to many hospitalisations and deaths worldwide. So it is fortuitous that Yanhusuo, far from having adverse liver effects, has been found to have liver-protective actions and so a side effect of this Chinese herbs turns out to be a beneficial one[7,8].
Improves cardiac circulation/ cardioprotective - Yanhusuo enhances coronary blood flow and to help protect cardiac muscle[9,10,11]. An important consideration in patients suffering from cardiac related pain. Yanhusuo is often used in hospitals in China and the Far East to treat cardiovascular diseases such as hypertension and cardiac arrhythmia[12].
Neuroprotective - Recent studies have shown neuroprotective effects such as anticholinesterase and anti-oxidant effects as well as reduced amyloid-β clumping suggesting Yanhusuo as a candidate substance to counter dementia and neuronal cell death[13].
Other benefits - Some studies have also supported the use of Yanhusuo as an anti-cancer agent[14] that may also reduce cancer-related muscle atrophy[15]. In diabetes care as it has been found to protect cells in the pancreas[16] and may even help with antibiotic gut microbiome injury[17]:
Time will tell whether Yanhusuo will become more widely accepted as a safe and multifunctional pain killer, especially with the obstacles that exist for the acceptance of plant-based medicines. Yanhusuo contains roughly 100 bioactive substances but drug licensing procedures are designed to only recognise single chemical entities as drugs. To single out one of these as the ‘main one’ would entail loss of the collateral benefits mentioned above and probably reduced efficacy as an analgesic. Also, drug patenting of natural substances is difficult – after all, who owns the intellectual property rights on the chemicals that nature generates?
Mega-profits are made when patents and mass market authorisations are obtained and, despite its advantages, this may not happen for Yanhusuo. That said, the traditional use that has been established in the context of China’s medical history means that you may benefit more from having Yanhusuo prescribed by a traditional physician formulating a bespoke treatment tailored specifically to you according to traditional wisdom than from a licensed drug version. Note. Chinese medicine is real medicine, safe and effective in the hands of trained professionals. It is not folk medicine and self-medication with any Chinese medicines is inadvisable. Corydalis is a big plant family each one with different properties, only a few species are used medicinally as Yanhusuo.
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