Role of the Endocannabinoid System in Pain Sensitivity

The endocannabinoid system controls hundreds of different mechanisms of homeostasis in humans. One of the most important roles of the endocannabinoid system is regulating pain sensitivity and the relationship between the immune system and both the peripheral and central nervous systems. The endocannabinoid system mediates the effects of phytocannabinoids on inflammation, which is the primary cause of pain in humans.

What is pain?

Pain is the biological response to damage or a perceived threat. Sensory nerves are equipped to identify potentially damaging mechanical (pressure), thermal (temperature), or chemical (toxic) threats; the physiological response of nerves to these stimuli is perceived as pain.

There are several roads that may lead to pain. At the most basic level, pain is understood to be the stimulation of certain nerve endings in the body. Pain may occur as a result of damage to body tissue, such as a laceration or crush injury. Pain can also occur without a known cause or long after a wound has healed. It can even occur when nerves have been disrupted or damaged.

Pain motivates an individual to avoid dangerous situations and to protect damaged body parts until healing can take place. For this reason, pain is also classified by its duration: short term (acute pain), and long term (chronic pain).

Acute pain is associated with a recent injury or surgery, and it typically resolves when the underlying damage heals.

Chronic pain is always lingering. It can last for months or even longer and eventually is labeled as a health condition in itself.

A nerve’s response to a threat is proportional to the relative danger posed by that threat; a dislocated shoulder is more dangerous than a papercut, so it’s also more painful. The degree to which a nerve responds to a given stimuli is known as pain sensitivity, and it’s a type of homeostasis that allows us to develop realistic relationships with the physical world around us. Pain sensitivity is controlled in several ways by the endocannabinoid system.

As life expectancy increases, chronic pain is becoming a very common condition; 80-plus years of wear and tear can certainly take their toll.

How does pain work?

To understand how pain works, one must first understand the peripheral nervous system. The peripheral nervous system is composed of all the nerves in the body, with the exception of those in the spinal cord and brain. This nerve network carries messages from the skin, muscles, and internal organs to the spinal cord and brain, which make up the central nervous system. When pain is experienced by a nerve in the periphery of the body, via multiple activation routes, the message is relayed to the spinal cord. There the pain signal is prioritized based on the nature and severity of it. For example, a burn will be processed as an urgent pain signal, while a scratch will be relayed in a slower manner.

The signal will then proceed up to the brain, bounce around to multiple areas and a return signal will be sent back down to the spinal cord, then to an effector of the body to carry out the response decided upon in the brain. Some responses are so fast, that in a split second a person could have removed their finger or hand from a hot stove before they even consciously registered the pain.

At the cellular level, pain can occur in multiple ways. When the glutamatergic system causes large quantities of the excitatory neurotransmitter, glutamate to be released into the synaptic cleft between two neurons, the result could be pain. In the case of migraines, calcitonin gene-related peptide has been found to be distributed in large quantities in the periphery of the body during a migraine.

In the unfortunate case of a jellyfish sting, the poison in jellyfish tentacles actually damages nerves in the affected area, sending a high priority signal to the spinal cord in a fraction of a second. The reason for this is that when nerves and neighboring cells begin to die they release factors into the bloodstream that alarm the rest of the body that they are unexpectedly dying and that an immune response must be mounted.

Are genes involved in pain sensitivity?

Pain sensitivity depends on the individual, especially on genes that determine how the endocannabinoid system is expressed. Genes determine how all of the different biological systems work, and although humans share about 99.8% of our genes, that 0.2% leaves a lot of room for variations. These variations lead to increased propensities for different conditions, including chronic pain.

In order to equip people with the knowledge contained in their own genetic code, MelixGX™ offers a cannabis DNA test that will tell you whether you have genetic traits that make you more likely to experience pain hypersensitivity, insomnia, anxiety, and depression. Melix is a genetic testing company based in South Florida which specializes in health and fitness genetic testing.

One of their products, MelixMJ™, gives you the resources you need to make informed decisions not only about your genetic likelihood of experiencing various conditions, but about the different kinds of cannabis products that your body will respond to best for each of those conditions. They determine the best strains, routes of administration (edible vs. smoked), and specific cannabinoids (CBD vs. THC) that your unique system will respond to best. Melix and companies like them are bringing the future of healthcare closer to us each and every day, with personalized solutions to problems which millions of people face.

What is the Role of the Endocannabinoid System in pain sensitivity?

In a recent study to determine how the cannabinoid system contributed to pain tolerance, laboratory rats had their CB1 receptors blocked using a known blocker molecule or antagonist of CB1 receptors, called rimonabant. The results of the experiment noted that, when the rats were given the antagonist to block their CB1 receptors, they experienced increased pain sensitivity, or hyperalgesia. Since then, more and more scientists conclude that the endocannabinoid system has an influential role in pain sensitivity.

Another research finding published in the National Library of Medicine in the last couple years discovered that THC stimulates beta-endorphin production. What this means is that by stimulating beta-endorphin production it can prevent the development of tolerance to and withdrawal from opiates. This is huge. Scientists believe that THC and other cannabinoids may have a promising application in the treatment of chronic pain and the opioid epidemic in the United States.

Can endocannabinoid deficiency affect pain sensitivity?

Dr. Ethan Russo, Senior Medical Advisor of GW Pharmaceuticals, stated that numerous age-related illnesses could in fact be caused because an underlying dysfunction or deficiency of tonic endocannabinoid system activity. Because the endocannabinoid system interacts with so many aspects of the body and because it parallels and interacts at many points with the other major endogenous pain control systems (endorphin/enkephalin, vanilloid/transient receptor potential (TRPV), inflammation, etc.) this is a very plausible theory as to the prevalence and causation of chronic pain disorders.

An endocannabinoid deficiency in the body would result in hyperalgesia or increased sensitivity to pain. In 2008, Ethan B. Russo published an article that cited a study conducted in the past that proved that blockage of CB1 receptors in mice lead to increased pain sensitivity. The endocannabinoid system has been known to inhibit the glutaminergic system previously mentioned, inhibiting the release of the excitatory neurotransmitter that causes pain, glutamate.

Cannabinoids presynaptically inhibit glutamate release, and calcitonin-gene related peptide. In the United States clinicians are tasked with detecting and treating pain that cannot be properly controlled by using only opiates. They fear addiction on one side and if they do not treat it then they face public scrutiny.

Physicians are seeking new approaches to treating the plethora of diseases plaguing our country; chronic pain is amongst the largest. Given that THC and other cannabinoids stimulate beta-endorphin production, preventing the development of tolerance and withdrawal from opiates, it is not strange to consider that cannabinoids may have a promising application in the treatment of chronic pain which may have its genesis in cannabinoid deficiency.