Pain and itch – two sensations that are really just intensified versions of the sense of touch.
Pain and itch play an important protective role. They alert to harmful stimuli and/or irritants. However, when the sensations become chronic, dogs suffer.
For years, scientists have longed to determine how closely itch and pain are related.
Historically, it was believed that the nerve cells for itch and pain were the same.
In the past few decades, researchers are discovering that the two sensations are distinct.
Why does it matter? If itch and pain nerve cells are separate, more effective, specific treatments can be developed.
A plethora of studies has led to an increased understanding of these two sensations. But the information is often conflicting or has changed as new discoveries are made. Most of the studies I have read ultimately focus on differentiating pain nerve cells from itch nerve cells in humans. However, much of the research is first studied using animal models.
In the mouse “cheek model,” the behavior responses to either painful or pruritic (itch-causing) stimuli are unique.
Specific chemicals are injected under the skin in the cheek pouch of the mouse.
The pruritogenic (itch-causing) substances (such as histamine, imiquimod, or formalin) result in the mouse scratching the site of injection with his hind foot, indicating itching.
The nociceptive (painful) sensations induced by injecting chemicals such as capsaicin (think chili peppers) and mustard oil, cause the mouse to wipe at his cheek with his front paw, indicating pain.
By studying the reactions of the mice, it might be possible to determine which medications are effective in blocking pain, itch, or both.
Both sensations start from the same place—a bundle of nerves at the base of the spine known as the dorsal root ganglion.
The endings of the itch-specific nerve cell fibers are located superficially in the skin and travel to the spinal cord. This is why you don’t feel itching in your internal organs.
The pain-detecting nerve fibers also extend into the muscle, bone, and internal organs. They allow you to feel pain in those areas. When a noxious substance activates a sensory nerve receptor (itch or pain), the receptors open up and depolarize the nerve cell, which transmits an attention-grabbing signal (pain and/or itch) through the spinal cord to the brain.
In 2007, a research team led by Dr. Zhou-Feng Chen, an investigator at Washington University’s Pain Center, discovered the first itch gene, named GRPR (gastrin-releasing peptide receptor).
This gene makes a receptor in the nerve cells that detect the pruritogen (itch-causing substance).
When mice were bred to omit the gene, they exhibited less scratching when exposed to the itchy stimuli than their normal littermates.
This is useful when we consider that many opioid pain medications (like morphine) have a common side effect of itching.
Chen and his colleagues were able to block painful stimuli by giving spinal injections of morphine. They found that the mice without the itch gene did not have the side effect of itching.
The investigators then showed that if they injected normal mice with a GRPR inhibitor, the morphine would still block the painful stimulus and the mice did not scratch.
In considering the different types of itch, scientists have separated them into two groups
1) Histamine-dependent itching
Histamine-dependent itching caused by bug bites or allergic reactions. Anti-histamine drugs are effective in blocking this type of itch.
2) Histamine-independent itching
Histamine-independent itching is the type found in over 50 diseases, such as shingles, AIDS, kidney disease, obsessive-compulsive disorder, and with medications such as opioids (like morphine) and antimalarials (like chloroquine). This type accounts for over 2/3 of chronic itching and currently has no effective treatment.
Another way to develop effective treatments for this type of chronic itch is to identify the itch-specific nerve cells.
Recently, Associate Professor Xinzhong Dong, of the Department of Neuroscience at Johns Hopkins School of Medicine did just that. He identified itch-specific nerve cells that had receptors (called MrgA3) for chloroquine, an anti-malarial drug widely used in Africa. As a side effect, this medication causes intense itching in up to 70% of black Africans, leading the patients to stop taking the important drug.
The researchers were now able to study these fibers by labeling them with a fluorescent protein to determine where they are located, how they are activated (i.e., what pruritogens can induce them) and how they could be de-activated (e.g., killing these itch fibers with a toxin eliminated or reduced the itch). This is an important step in developing medications that can block chronic itch. Professor Dong hints that it may only be a matter of a few years before this is realized.
How does all this pertain to our canine companions?
We can extrapolate that they have the same types of itch and pain sensations as humans, so this on-going research will likely provide benefits to both species in the near future. Medications and treatments that eliminate chronic itch due to a large number of causes might be available within a few years and will undoubtedly lead to an improved quality of life.
Chronic Versus Acute Pain In Dogs: What Is The Difference?
The multiple pathways for itch and their interactions with pain