Opioid misuse is a worldwide problem, affecting an estimated 15 million people per year.¹⁰ In order to combat this issue, biomedicine is turning to more natural medical approaches in search of safe and effective pain treatment strategies.

From both traditional and modern perspectives, specific herbs within the scope of Chinese herbal medicine are found to be advantageous in the treatment of pain as it relates to opioids.

Let's discuss the biological mechanisms of opioids and Chinese herbal strategies that target opioid receptors in the body.

How The Endogenous Opioid System Affects Pain

The endogenous opioid system in the human body has several functions, including the modulation of the body's response to pain. Activation of opioid receptors influences enzymes and nuclear gene transcription, and modulates ion channels in the neurons upon which they are expressed.¹⁵ These processes inhibit pain signals from reaching the brain,¹ but fail to alleviate the true sources of pain.

There are various types of opioid receptors found in the human body. The major subtypes include delta (δ), kappa (κ) and mu (µ).1 Hydrocodone, for example, is primarily a µ-receptor agonist. µ-opioid receptors have a high affinity for endogenous substrates such as beta-endorphin and enkephalin, but they are also the main receptor targets for exogenous compounds such as morphine and codeine.¹⁵

They are found pre- and post-synaptically in brain regions involved in cognition, sensory perception, reward and addiction, and in the dorsal horn of the spinal cord, where sensory input ascends to the brain.^7,9 µ opioid receptor-expressing neurons are also concentrated along the small intestine, stomach and proximal colon of the intestinal tract,¹³ and activation of these receptors prevents peristaltic movement in the intestines by inhibiting the function of the enteric nervous system.⁵

The Papaveraceae Plant Family and TCM

Pharmaceutical opioid drugs are derived from chemicals found in the Papaveraceae plant family. Within Chinese medical herbology, two significant herbs are found in this plant family: ying su ke (Papaveris pericarpium) and yan hu suo (Corydalis rhizoma).²

Ying su ke is part of the opium plant and is an obsolete substance in the Chinese herbal materia medica.² It is a natural source of µ-opioid receptor agonists including morphine and codeine.¹¹ The main indication for this herb in traditional Chinese medicine is not for pain; instead, this herb is utilized for its astringent nature. It is found in the Stabilize and Bind category and enters the lung, large intestine and kidney channels.

This herb is indicated for cough and diarrhea. Its secondary action is the treatment of pain in the chest, sinews and bones.²

Using this traditional information about ying su ke, as well as the fact the µ-opioid receptors are found in the intestinal tract, it becomes clear that µ-opioid receptor agonists (such as pharmaceutical opioids) should only be prescribed if the patient is experiencing diarrhea or cough concurrently with their pain. Using this drug type without these indications may result in respiratory depression and decreased peristalsis in the intestines (two common side effects of opioid prescriptions).¹⁵

Yan hu suo (Corydalis rhizoma) is a second herb found in the Papaveraceae plant family. It is in the Blood Invigorating category of the TCM material medica. Yan hu suo is acrid, bitter, warm, and enters the heart, liver, and stomach channels. The function of this herb is to invigorate blood and strongly stop pain.² It is found in blood-invigorating formulas such as Ge Xia Zhu Yu Tang and Shao Fu Zhu Yu Tang.¹²

Yan hu suo (Corydalis rhizoma) contains many bioactive components, and each of these molecules contributes to the different pain-relieving qualities of the herb. The actions of these molecules are not limited to µ-opioid receptors, but are also shown to affect κ-opioid receptors and dopaminergic D-2 receptors.^16,18-20

One of these alkaloids, tetrahydropalmatine (THP), has been suggested to have a preventative effect on drug-seeking behavior. In three separate mouse studies, ingestion of THP decreased self-administration of heroin (diamorphine), methamphetamine and cocaine, respectively.^8,14,17 These studies suggest yan hu suo intrinsically inhibits the herb from becoming addictive, and may also be advantageous in treating drug addiction.

Incorporating Yan Hu Suo into Clinical Practice

Yan hu suo can be used as a modification to Chinese herbal formulas when appropriate for the patient's presentation. The typical therapeutic dosage for yan hu suo is 3-9 grams per day of the crude, dried herb. At a dosage of 10-15 grams, patients may begin to feel side effects such as drowsiness, dizziness or abdominal distention.

At high dosages of 60-120 grams, patients start to experience toxicity symptoms. These side effects mimic the side effects of hydrocodone and include dizziness, drowsiness, dyspnea, facial pallor, low blood pressure, weakness, spasms, weak pulse, shock, convulsions, and respiratory failure. The patient may also experience symptoms of allergic reactions, which include dizziness, erythema, fever, nausea, pruritus, shortness of breath, and numbness of lips and extremities.²

For patient safety, yan hu suo should be use at a maximum dose of 20 grams to avoid toxicity symptoms. Intake of yan hu suo should be avoided during pregnancy or when nursing, and should be used with caution in patients with underlying deficiency, as this herb may consume qi and blood.³

Vinegar-fried yan hu suo provides the most analgesic effect. From a TCM perspective, this is because the vinegar-fried preparation enters the liver channel more directly. From a biochemical perspective, vinegar-frying makes the alkaloids in the herb more available.² It has also been suggested that concurrent use of yan hu suo with electroacupuncture is synergistic in treating pain.^3,6

When using electroacupuncture, it has been shown that 2 Hz frequency is able to activate µ receptors, 100 Hz activates κ receptors, while 10 and 15 Hz electro-acupuncture activate δ, κ and µ receptors simultaneously.¹⁸

Transform Pain Management

Health care systems worldwide are in need of improved standards of care for pain management and opiate drug use. Traditional Chinese medicine is a proven and safe treatment option, free of the complications and side effects typically found with pharmaceutical opiates, including drug dependence, tolerance and addiction.

Chinese herbs such as yan hu suo, in conjunction with effective pain-targeting modalities such as acupuncture,⁴ have been shown to modulate the endogenous opioid system and treat pain using molecular mechanisms that are more multifaceted than standard prescription opiates alone. By understanding this issue from both a biomedical and Chinese medical perspective, TCM practitioners can offer effective and informed treatment options to this patient population.

References

1. Al-Hasani R, & Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiol, 2011;115(6):1363-81.
2. Bensky D, et al. Chinese Herbal Medicine: Materia Medica. Eastland Press, 2016.
3. Chen JK, et al. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press, Inc., 2012.
4. Fan AY, et al. Acupuncture's Role in Solving the Opioid Epidemic: Evidence, Cost-Effectiveness, and Care Availability for Acupuncture as a Primary, Non-Pharmacologic Method for Pain Relief and Management –White Paper 2017. J Integrative Med, 2017;15(6):411-425.
5. Holzer P. Opioid receptors in the gastrointestinal tract. Regulatory Peptides, 2009;155(1-3):11–17.
6. Hu J, et al. [Effect of some drugs on electroacupuncture analgesia and cytosolic free Ca2 concentration of mice brain]. Acupuncture Research, 1994;19(1):55–58.
7. Kline RH, & Wiley RG. Spinal µ-opioid receptor-expressing dorsal horn neurons: role in nociception and morphine antinociception. J Neurosci, 2008;28(4):904-913.
8. Mantsch JR, et al. Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. Pharmacol Biochem and Behavior, 2010;97(2):310-316.
9. Merrer JL, et al. Reward processing by the opioid system in the brain. Physiological Reviews, 2009;89(4):1379-1412.
10. Opioid Addiction. Genetics Home Reference - NIH. https://ghr.nlm.nih.gov/condition/opioid-addiction
11. Pathan H, & Williams J. Basic opioid pharmacology: an update. British J Pain, 2012;6(1):11-16.
12. Scheid V, et al. Chinese Herbal Medicine: Formulas & Strategies. Seattle, WA: Eastland Press, 2009.
13. Sternini C, et al. The opioid system in the gastrointestinal tract. Neurogastroenterol and Motility, 2004;16(s2):3-16.
14. Su H-L, et al. Roles of levo-tetrahydropalmatine in modulating methamphetamine reward behavior. Physiology & Behavior, 2013;118:195-200.
15. Trescot AM. Opioid pharmacology and pharmacokinetics. Controlled Substance Management in Chronic Pain, 2016:45–62.
16. Wang JB, & Mantsch JR. l-tetrahydropalamatine: a potential new medication for the treatment of cocaine addiction. Future Medicinal Chem, 2012;4(2):177-186.
17. Yue K, et al. The dopamine receptor antagonist levo-tetrahydropalmatine attenuates heroin self-administration and heroin-induced reinstatement in rats. Pharmacol Biochem and Behavior, 2012;102(1):1-5.
18. Zhang R, et al. Mechanisms of acupuncture – electroacupuncture on persistent pain. Anesthesiology, 2014;120(2):482-503.
19. Zhang Y, et al. Discovery of N-methyltetrahydroprotoberberines with κ-opioid receptor agonists-opioid receptor agonist activities from corydalis yanhusuo W. T. Wang by using two-dimensional liquid chromatography. J Ethnopharmacol, 2014;155(3):1597-1602.
20. Zhang Y, et al. A novel analgesic isolated from a traditional Chinese medicine. Curr Biol, 2014;24(2):117-123.

---

Ashley Davis has a BS in Neuroscience from the University of Illinois and a Master of Science in Traditional Oriental Medicine from PCOM. She owns an acupuncture / herbal clinic in Lincolnshire, Ill., and is currently pursuing her Doctor of Acupuncture and Chinese Medicine from PCOM.

Next Article in Issue

Previous Article in Issue