PROVIDENCE, R.I. - Pain triggers the brain's release of a naturally produced cannabinoid, a compound similar to the active ingredient in marijuana, according to a new study by Brown researchers that documented its release in the brain's pain response system for the first time.
The cannabinoid known as anandamide produced analgesia - the absence of a normal sense of pain - in response to pain in anesthetized rats. The findings are published in the Oct. 12 issue of the Proceedings of the National Academy of Sciences (PNAS).
Although the existence of non-opiate factors in the brain's pain suppression system were first noted 20 years ago, little was known about these substances. Brown researchers were able to measure the anandamide using a new type of mass spectrometry, which is able to detect minute amounts of a substance.
Knowledge about a pain-modulatory system based on cannabinoids is valuable for the future treatment of pain, particularly in instances where opiates are ineffective, according to J. Michael Walker, psychology professor and lead researcher.
"There are some types of pain that do not respond well to current treatments," said Walker. "The fact that you have different modulatory systems that are effective for different types of pain may offer hope."
Drugs that inhibit the reuptake of anandamide by cells, or block its degradation, may form the basis of a modern pharmacotherapy for pain, he said.
Researchers measured the levels of anandamide in the region of the brain recognized for its role in pain modulation - the periaqueductal gray (PAG). The PAG is part of the brain stem that connects the cerebral hemispheres with the spinal cord. It is very similar in animals and humans.
Electrical stimulation of the PAG in anesthetized animal models was accompanied by both pain suppression and a marked increase in the release of anandamide. Furthermore, injections of formalin, a chemical irritant that induces prolonged pain, profoundly elevated the anandamide levels in the same location of the PAG in anesthetized rats. Although animals did not feel the pain, researchers were able to observe pain modulation because the brain responds in the same way.
Researchers used atmospheric pressure-chemical ionization mass spectrometry to measure the molecular weight of anandamide. This multistep method permitted the detection of the extremely small amounts of the anandamide. They found the substance in a different location of the PAG than the location proven to play a part in the release of natural opiates.
"One of the functions of chemical transmission in the brain is to modify pain sensitivity, and the brain uses the anandamide for this purpose," said Walker. "The pain itself triggers this reaction."
The correlation between cannabinoids and pain suppression is not a startling finding in itself; cannabinoids have been used to treat pain for centuries. In ancient China, hemp extract was used as a surgical anesthetic, and archaeological finds in Israel have revealed its use against the pain of childbirth.
Cannabis is still used to treat pain, despite its illegal status in most parts of the world. A report early this year by the National Academy of Sciences Institute of Medicine found that significant amounts of research - including research by Walker and colleagues - point to the potential to use marijuana derivatives in treating chronic pain.
However, more research needs to be done to determine whether there are other naturally produced cannabinoids released in the brain in addition to anandamide, said Walker.
Other researchers involved in the study were Susan M. Huang, Brown graduate student; Nicole M. Strangman, Brown graduate student; M. Clara Saûudo-Peûa, assistant research professor of psychology; and the late Brown University professor and member of the Chinese Academy of Sciences, Kang Tsou. The work was supported with funding from the U.S. Public Health Service and National Institutes of Health. In addition, Brown University and the National Institute on Drug Abuse financed the purchase of the mass spectrometer used in the experiments.
Journal
Proceedings of the National Academy of Sciences