“Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable.
Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum.
Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups.
Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine.
This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.”
“Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered 
“Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system.
“Many Americans rely on opioids at varying dosages to help ameliorate their suffering. However, empirical evidence is mounting that opioids are ineffective at controlling non-cancer related chronic pain, and many argue the strategies meant to relieve patient suffering are contributing to the growing opioid epidemic.
“It is thought that endogenous cannabinoids have a role in the analgesia induced by specific forms of stress.
“Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.