Readers my age would recall the Marilyn Monroe movie, “Seven Year Itch”, which highlighted how men, bored with their 7-year-long marriage to the same wife, begin extramarital wandering. As it turns out, the phrase did not refer to the urge to infidelity at all; it was coined in the 19th century to describe a skin infection that American soldiers suffered from, for over seven years; it was also called the Army Itch or the French Itch (when they went to France and caught the infection). Thus, there are itches and itches.

But an itch is different from pain, or is it? Most languages have distinct words for each. In Tamil, itch is “Arippu”, and different from “Vali” for pain. And in Hindi, “Khujli” is different from “Dard”.

Some even have words that distinguish pain from ache (though not Tamil or in Hindi). Itch is a skin-related complaint, brought about by infection, dry skin or by substances that provoke the release of the allergy-producing chemical histamine. Itch provokes scratching for relief and may be temporary or chronic. For chronic cases, doctors prescribe anti-histamine medication.

Pain is a more general term, but it is not restricted to the skin. It comes on suddenly, can be local or widespread, and can be mild or acute. Ache, on the other hand, is persistent, generally restricted to an area or organ and is chronic. Ache does not hinder you from doing something while pain does.

And ache comes out of tiring, say of muscles for example, and lasts a while. Unlike pain, it is persistent and dull. It is the body’s signal to take suitable remedial measures.

Researchers have been debating on whether or not pain and itch are the same, closely related, and physiologically related or distant. Some resolution seems in the offing, thanks to some recent work by Dr. Zhou-Feng Chen of the Washington University of Medicine Pain Centre at St. Louis, MD, USA, and his colleagues. There are some distinctions.

For one, molecules that receive the itch signal (called itch receptors) are confined to the top two skin layers — the epidermis and dermal transition layers.

Second, the molecule histamine is invariably associated with itch. Third, while mechanical stimuli, heat and substances like capsaicin (contained in chilli peppers) cause pain, they do not make you scratch. And while itching generates the scratching reflex, pain leads to the withdrawal reflex.

Yet, itch had long been held by physiologists to be a sub-modality or sub-quality of pain and both sensations have many similarities. Whether they are mediated by distinct neural circuits has also been an issue. Dr. Chen’s group has addressed these questions, first in their 2007 paper in Nature, and now in the 6 August issue of Science.

The earlier paper

In the earlier paper, they showed that there is a specific gene called GRPR, associated with causing the itch sensation. GRPR was seen to be present in very few nerve cells which are known to send pain or itch signals to the brain. They compared the itching behaviour of normal mice with those that lacked the GRPR gene.

Upon applying a bit of a pruritogen (fancy Latin name for an itch producing substance) on their skins, the GRPR-less mice scratched far less than normal mice. However, both sets of mice reacted to pain (upon touching a hot plate, or upon pasting a pain producer) the same way.

This meant that pain and itch are governed by separate genes and neural circuits. It also meant that drugs that can treat itching need not suppress pain. After all, pain is a protective sensation that alerts the body to danger.

It was around the same time that Dr. Geoffery Woods of Cambridge University, U.K., was studying an unusual Pakistani family, where some members were born with no pain sensation at all.

Gene mutations

Analysis revealed that mutations in the gene SCN9A, associated with electric conduction in nerve cells (though voltage gated sodium channels), caused this illness. There are other cases of children born with congenital insensitivity to pain with anhidrosis (CIPA) and its more common forms, hereditary sensory and autonomic neuropathy (HSAN) and familial dysautonomia (FD). These unfortunate children suffer enormously due to their inability to feel pain, hurt themselves so badly, and ultimately die early deaths. Thus, let us not underestimate the value of pain. Pain is gain.

And thankfully, pain and itch have different neural routes, or distinct labeled lines. In their latest paper, Dr. Chen and associates took normal mice and, using specific toxins, killed nerve cells, called lamina I neurons, expressing GRPR in their spinal cords. These mice lost scratching sensations, no matter what itching agent was used, but their pain behaviour was unaffected.

Work of this kind is important, since it now becomes possible to develop new approaches, and may be new drugs, that will address the issue of itching, psoriasis, eczema and related conditions.

Email: dbala@lvpei.org

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