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In the ongoing quest to identify pain treatments with fewer adverse effects than those commonly used, researchers at the University of California Irvine and the Chinese Academy of Sciences in Dalian, China, investigated the antinociceptive properties of a Chinese herb that has long been used for pain relief.1
Plant extracts have been used to treat pain for centuries. Perhaps most notable to western medicine are aspirin, which was initially developed from salicin, a chemical in willow bark , and opioids, which originated from the opium poppy.2
In traditional Chinese medicine, the Corydalis yanhusuo W.T. Wang (YHS) herb has been used to treat pain and inflammation for more than 1,000 years.
“There is a growing interest in finding therapies that act not on one single target but instead are multi-targeted–we call this polypharmacology,” said study co-author Olivier Civelli, PhD, a professor of pharmacology, pharmaceutical sciences, and developmental and cell biology at the University of California Irvine. “YHS is a mixture of alkaloids that together can have a different analgesic effect than isolated drugs,” he told Clinical Pain Advisor.
Previous research demonstrated the antinociceptive properties of 2 isolated alkaloids of YHS, l-tetrahydropalmatine (l-THP) and dehydrocorybulbine (DHCB).3,4 Dr Cipelli and colleagues aimed to build on those findings by investigating the analgesic effects of the full YHS extract in rodent models of acute, inflammatory, and neuropathic pain.
Mice were administered different doses of either morphine, YHS, a vehicle solution, or a mixture of the isolated alkaloids l-THP and DHCB, before being subjected to standardized tests to assess pain behavior following spinal nerve ligation, and which included the tail-flick assay, the formalin paw licking assay, the von Frey filaments assay, and the Hargreaves assay.
According to the results, YHS (500 mg/kg) showed significant antinociceptive effects in the tail-flick assay (P <.001), while a combination of its isolated compounds showed no such effect (P >.05). Results from the other 3 assays indicate antinociceptive effects on acute, inflammatory, and neuropathic pain at a non-sedative dose (200 mg/kg), compared to the vehicle solution, which had no effect.
In addition, experiments comparing wild-type mice and dopamine D2 receptor knockout (D2KO) mice revealed that the analgesic mechanisms of YHS are at least partially due to D2 receptor antagonism.
However, these effects were observed for acute and neuropathic, but not inflammatory, pain. Further testing showed that daily administration of YHS for 7 days did not lead to tolerance of its antinociceptive effects, unlike morphine (P <.01).
YHS presents a potential new treatment option for neuropathic pain management, without the tolerance observed with many analgesic drugs.
“Another benefit is that, because YHS acts, at least in part, as an antagonist to the dopamine receptors, it should not display addictive properties, which is a major issue in pain management these days,” explained Dr Civelli. Because “YHS is readily available as a supplement in the US, and it can be used by patients without prescription, clinicians could prescribe it as an adjunct therapy,” he added.
In future research, he would like to test the effects of combining YHS with commonly used analgesics to possibly prevent their overuse. He noted that research on “natural medicine” is not well-received by institutions that support basic research, partially because of the relative novelty of poly-pharmacology, which is inherent to plant-based medicine.
“For that to begin to change, we will need to decrease the power of the pharmaceutical industry on academic research. Maybe the fact that countries like China are taking their traditional medicines seriously will be a catalyst for change,” he said.
Limitations and Disclosures
Future studies should elucidate the role of D1 and D2 receptors in the antinociceptive effects of YHS, and clinical trials should be conducted to further test efficacy and safety in humans.
The authors declare that they have no conflicts of interest to disclose.
References
- Wang L, Zhang Y, Wang Z, et al. The antinociceptive properties of the Corydalis yanhusuo extract. PLoS ONE. 2016; 11(9): e0162875. doi:10.1371/journal.pone.0162875.
- University of Maryland Medical Center. Willow Bark. Retrieved 9/21/16 from http://umm.edu/health/medical/altmed/herb/willow-bark
- Hu JY, Jin GZ. Supraspinal D2 receptor involved in antinociception induced by l-tetrahydropalmatine. Zhongguo Yao Li Xue Bao. 1999; 20(8):715-719.
- Zhang Y, Wang C, Wang L, et al. A novel analgesic isolated from a traditional Chinese medicine. Curr biol. 2014; 24(2):117–123.
