How Cannabis inhibits and modulates Pain via COX-2?
Pain and inflammation are a part of our body’s defense system and are important mediators of the immune functions in the body. The primary role of pain/inflammation is to help identify the sites of injury in the body cells and tissues and trigger an immune response to it.
Mechanism of Pain and inflammation in body
During any injury, the injured body cells release chemical compounds that inform body cells and body tissues to retribute by stimulating the immune cells of the body. The injured nerve endings of the body cells trigger a series of pain/inflammatory stimuli that awaken the immune system and begin to produce a defensive action near the injury. These chemical compounds and nerve stimuli release a number of immune cells at the injured sites and enhance their production of antibodies. Apart from this they also activate secondary mechanisms like blood clotting factors, increase the absorption of body nutrients, modulate temperature to activate other essential immune compounds that speed up tissue recovery. These mechanisms co-exist at every injured site, and work synergistically in repairing the injured tissues/cells and also clearing out accumulated debris in the wounds. The problem arises when these mechanisms go out of balance, and the body is unable to manage the harmony in the healing process. This causes an unwanted and disharmonious accumulation and production of certain compounds that cause increased pain and inflammation and disturb the natural chain of cell recovery mechanisms.
Painkillers and pain
The rise in the need for painkillers and anti-inflammatory medicines that could help modulate these mechanisms via external resources, became a necessary evil in the system. The role of analgesics and anti-inflammatory in treating acute as well as chronic conditions was defined as they can decrease the ‘uncontrolled’ pain/inflammation- causing compounds and stimuli that the body becomes incapable of managing easily. These drugs and medicines were formulated to target body enzymes and other compounds that have a pain-giving action and also decrease the production of such compounds. Although these enzymes are naturally manufactured in the body, at certain times the body becomes incapable of managing their production, which eventually accelerates pain and inflammation at the injured site.
Role of Prostaglandins in pain
Prostaglandins are one such group of pain-causing compounds manufactured naturally in the body as an outcome of any injury. They are produced as a byproduct of any membrane injury of body cells and have a very potent, hormone-like painful effect on the body tissues. They have a widespread effect on the body's blood supply, contraction of the body, respiratory effect, blood pressure etc. that induce persistent pain at these injured sites. It was later discovered that these lipid-based compounds were a result of the catalytic stimulation of enzymes called ‘ cyclooxygenases’. The cyclooxygenases, especially COX-2, are responsible for the production of most types of prostaglandins in the body and enhance the mechanisms of tissue pain and inflammation in the body.
Cannabis inhibition on COX-2 for pain relieving effect:
The Cannabis plant is composed of potent plant-compounds that regulate and modulate the production of COX-2 and also inhibit the activity of the cyclooxygenases. The main plant-compounds in this plant, also called ‘phytocannabinoids’, like THC, CBD, CBVG, CDBG etc. mimic the action of modern painkillers but produce a larger effect with much fewer dosages. Their pain-modulating effect treats the root cause of the disharmony and deficiencies in the body cells and strives to bring a balance in the recovery mechanism in tissues. The phytocannabinoids modulate and decrease the stimulation of pain/inflammation nerve stimuli that trigger COX-2 synthesis, and control its production via the nervous system. Their large action on deactivation of the action of COX-2 but also decrease in their production on the genetic levels, helps in spontaneous decrease in pain mechanisms. It was observed that these compounds could selectively target areas of the chemical structure of the COX-2 compound and spontaneously deactivate and decrease its action on body tissues.
References:
https://pubmed.ncbi.nlm.nih.gov/18556441/
https://lab.vanderbilt.edu/marnett-lab/endocannabinoid-oxygenation-by-cox-2/