Background & Aims
With increased efforts towards finding alternative treatments to opioids, attention is turning to new treatment targets for chronic pain. 5HT serotonin receptor agonist ‘psychedelic’ drugs, such as psilocybin, have sparked increased interest over the past 10 years particularly in the field of cognitive disorders such as depression. More recently, there has been growing interest in the effect of psilocybin on chronic pain. Still, while there is an abundance of anecdotal evidence to support the benefits of psilocybin in conditions such as lower back pain, migraines, cluster headaches and fibromyalgia, this research aims to provide strong, empirical, mechanistic evidence to conclusively investigate the effect of psilocybin in chronic pain.
This research aims to test the ability of psilocybin to reduce pain-like behaviour in a model of neuropathic pain induced by peripheral nerve injury and to investigate potential mechanisms of action underlying analgesic effect.
Methods
For this project, we used the Spared Nerve Injury (SNI) model of peripheral neuropathy (Decosterd and Woolf, 2000). This model induces robust mechanical and thermal hypersensitivity. Psilocybin (0.3mg/kg or 1mg/kg) was administered intraperitoneally when maximum hypersensitivity developed. We analysed static allodynia using the Von Frey test, dynamic allodynia using a brush test in the hind paw, and cold hypersensitivity using the acetone test. Finally, we investigated locomotory function using the rotarod test. Real time quantitative polymerase chain reaction (RT-qPCR) was carried out to assess changes in the 5-HT2A receptor levels following pain-state induction and injection of psilocybin.
Results
A single injection of psilocybin produced a significant long-term reduction in mechanical sensitivity. This was shown by a significant increase in the 50% withdrawal threshold, and a reduction in dynamic allodynia for up to 10 weeks post-injection. Cold hypersensitivity was significantly reduced in the psilocybin-injected group, shown by a reduction in the time spent licking and biting the paw following the application of acetone during the acetone test. No adverse effects on balance and coordination were observed in the SNI mice injected with psilocybin, but rather a trend towards increased performance was seen. Preliminary data also suggested changes in 5-HT2a receptor transcript levels at the level of the spinal cord, a trend towards an increase in the cortex after SNI surgery, as well as changes following psilocybin injection.
Conclusions
Our data strongly indicate that a single injection of psilocybin provides long period of relief from neuropathic pain. Our ongoing experiments suggest that these actions may be linked to changes in 5-HT2A receptor levels.
References
Decosterd, I., Woolf, C.J., 2000. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87, 149–158. https://doi.org/10.1016/S0304-3959(00)00276-1
Majedi, H., Dehghani, S.S., Soleyman-Jahi, S., Tafakhori, A., Emami, S.A., Mireskandari, M., Hosseini, S.M., 2019. Assessment of Factors Predicting Inadequate Pain Management in Chronic Pain Patients. Anesthesiol. Pain Med. 9, e97229. https://doi.org/10.5812/aapm.97229