Cannabinoid receptors are known to be located all throughout the body. Although most abundant in the central and peripheral nervous system and in immune system cells, cannabinoid receptors are also thought to reside in other types of tissues. However, due to the number of possible locations and the number of experiments necessary to establish localization of those receptors, new areas are still being discovered more than two decades after the discovery of the receptors themselves.
Why do we care? If we are interested in the medicinal effects of cannabis and cannabinoids, research focusing on the actual effects of cannabinoids and inhibitors may seem more to the point. Regardless of the localization of the receptors, the bottom line is whether the endocannabinoid system can or cannot be a pharmaceutical target for a given medical condition. This assumes that we already know the conditions we are seeking to cure or treat. Building a functional map of the distribution of receptors throughout the body, while time and labor-intensive, will also likely reveal new conditions that may be associated or even be a direct result of endocannabinoid system operation.
This year, a research group from the University of Padua in Italy decided to use samples of myofascial tissue to test for the presence of endocannabinoid receptors. Myofascial tissue is essentially an organic mesh of collagen that has a great strength while at the same time is highly flexible. This type of tissue is employed all throughout the body to keep organs compartmentalized as well as to provide support and protection for muscles since it allows growth and movement. Normally this tissue is able to adjust as needed. However, when trauma or disease causes the tissue to harden or decrease its elasticity, pain results as components of the body find themselves forced up against the tissue with inadequate room to move. Myofascial problems are, therefore, one of the primary causes of muscle pain (Myofascial Pain Syndrome). Unfortunately, few treatments are available, other than standard pain killer options and pharmaceuticals with strong side effects.
Researchers from Padua sought to establish the existence of cannabinoid receptors in this type of tissue, but unfortunately, acquiring samples can be difficult, since it requires minor surgery. As a result, researchers cleverly asked permission to extract small tissue samples from patients already undergoing orthopedic surgery. From there, researchers sought to confirm or deny the existence of cannabinoid receptors via two methods. For the first, researchers cut very thin samples from the original tissue samples and used special stains that only bond to proteins that produce cannabinoid receptors. They then prepared these for viewing/photographing under a microscope, thus revealing a directly visual account of cannabinoid receptors locations within a cell.
Secondly, researchers further broke apart these cells to release their RNA (think of this as a working form of DNA) and then used chemical tracers that bond to cannabinoid receptor proteins and give off light. By using a photometer that measures the light given off, researchers can then get an accurate headcount of the receptors in a given tissue sample without being able to count receptors individually. This process is generally regarded to be one of the best ways to investigate new receptor locations.
In both cases, readers may not be surprised to learn that both types of cannabinoid receptors, CB1 and CB2, are present in myofascial tissue. While researchers noted that samples had a degree of variability in cannabinoid receptor expression, all samples at least contained a significant amount of both types of receptors. In the first experiment, microscope slide images showed markings that were distributed horizontally in lines, which would make sense, as the receptors are embedded in muscle cells that form long muscle fibers.
Graph inset: Microscope slide image showing stained CB1 receptors (Image I) and CB2 receptors (Image J) in myofascial fibroblast cells.
Researchers confirmed these results and took measures to assure no DNA contamination, thus offering the first formal proof of cannabinoid receptors in such tissues.
Fibromyalgia may be one important condition affected by this research. One obvious connection is that fibromyalgia is characterized by a general skeletal-muscular pain caused by inflammation of myofascial tissue. Frequent readers will remember that cannabinoids and especially CBD are capable of treating many types of inflammation and over-response in tissues. Now that we know for sure cannabinoid receptors exist in the type of tissue that causes fibromyalgia, we also know that cannabiniod receptors could help play a role in reducing that inflammation. At the time being, patients suffering from fibromyalgia may consider using cannabis or CBD to alleviate muscular pain.
Fede, G. Albertin, L. Petrelli, et al. Expression of the endocannabinoid receptors in human fascial tissue. European Journal of Histochemistry (2016) 60:2643.