Pain And Itch in Dogs: Are They Two Sides Of The Same Coin?

Are pain and itch just intensified versions of the sense of touch?

Are Pain and Itch the Same—or Different?

Pain and itch play an important protective role. They alert dogs to harmful stimuli and irritants. When these sensations become chronic, however, they cause suffering.

For years, scientists have tried to determine how closely itch and pain are related. Historically, researchers believed the same nerve cells transmitted both sensations. Over the past few decades, researchers have shown that pain and itch are closely connected but ultimately distinct sensory experiences. They share some of the same signals in the brain but travel along different pathways.

Why does it matter?

If itch and pain follow separate pathways, this allows for more targeted treatments.

Studies have increased our understanding of pain and itch, but findings are not always consistent and continue to evolve. Much of the research focuses on distinguishing pain from itch in humans, although many discoveries begin in animal models.

The Mouse “Cheek Model”

In the widely used mouse “cheek model,” researchers inject pruritogenic chemicals (like histamine) or nociceptive agents (like capsaicin) into the cheek of mice and observe distinct behaviors—scratching for itch vs wiping for pain—allowing scientists to study how different sensations are processed in the nervous system. PMC

By studying these distinct responses, researchers can evaluate whether medications block pain, itch, or both.

Where Do Pain and Itch Signals Begin?

Both sensations begin in a cluster of sensory nerve cells at the base of the spine called 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.

Pain-detecting nerve fibers extend into muscle, bone, and internal organs, allowing you to feel pain in those areas. When a noxious substance activates a sensory receptor, the receptor opens and depolarizes the nerve cell, which then sends a signal through the spinal cord to the brain.

First Itch-Specific Gene Discovered

In 2007, a research team led by Dr. Zhou-Feng Chen at Washington University identified the first itch-specific gene, GRPR (gastrin-releasing peptide receptor). GRPR encodes a receptor found in spinal nerve cells that respond to pruritogens—substances that trigger itch.

When researchers bred mice lacking this gene, the animals scratched significantly less in response to itch stimuli than their normal littermates. This discovery confirmed that itch is not simply a weaker form of pain, but a distinct sensory pathway.

The finding is clinically important because many opioid pain medications, including morphine, commonly cause itching as a side effect.

Chen’s team showed that spinal injections of morphine still blocked pain in mice lacking GRPR—but without triggering scratching. Further experiments demonstrated that blocking GRPR in normal mice allowed morphine to relieve pain without inducing itch.

Not Every Itch Is the Same

Scientists divide itch into two main types.

Itch-Specific Nerve Cells

Another strategy for developing effective treatments for chronic itch is identifying the nerve cells that drive it.

Associate Professor Xinzhong Dong at Johns Hopkins School of Medicine identified itch-specific nerve cells that carry receptors called MrgA3, which respond to chloroquine, an antimalarial drug widely used in Africa. As a side effect, chloroquine causes intense itching in up to 70% of Black patients, sometimes leading them to stop taking this important medication.

By labeling these nerve fibers with a fluorescent marker, researchers were able to determine where the cells are located, how they are activated (that is, which pruritogens trigger them), and how they can be turned off. In experimental models, selectively eliminating these itch fibers significantly reduced scratching.

This work marks an important step toward developing medications that can block chronic itch at its source.

Editor’s Note: Latest Research Updates

Since many of the foundational discoveries described above, veterinary medicine has made significant advances in treating chronic itch and pain in dogs.

Some newer therapies aim to target specific molecules and pathways involved in itch and pain, rather than broadly suppressing inflammation.

Chronic Itch Treatments

For chronic itch—particularly allergic and atopic dermatitis—newer treatments include:

Chronic osteoarthritis pain treatments

For osteoarthritis pain, monoclonal antibody therapies targeting nerve growth factor (NGF) have emerged as an additional option for pain management in dogs.

Nerve growth factor (NGF) monoclonal antibodies are designed to reduce osteoarthritis pain by blocking pain signaling rather than suppressing inflammation. While many dogs experience improved mobility and comfort, post-approval monitoring has identified rare neurological and mobility-related adverse events in some cases. Ongoing surveillance continues to evaluate risk factors and appropriate patient selection.

Anti-NGF monoclonal antibodies

e.g. Librela (bedinvetmab)
target nerve growth factor (NGF), a key mediator of osteoarthritis pain signaling

What it may help with:

• reduction of osteoarthritis pain in dogs
• improved mobility and activity levels in some dogs
• monthly injection option for long-term management

Potential adverse effects / considerations:

Gastrointestinal side effects are uncommon compared with NSAIDs, but different risks exist

• reported adverse events include lethargy, ataxia (uncoordinated movement), weakness, and other neurological signs in some dogs
• response varies between individual dogs
• careful patient selection and ongoing veterinary monitoring are important
• long-term safety data continue to accumulate

Editorial note: Nerve growth factor (NGF) plays a role not only in pain signaling but also in normal nerve function and repair. Blocking NGF can reduce pain perception, but it also alters signaling pathways involved in sensory processing.

For that reason, post-marketing surveillance has reported neurological signs in some dogs treated with anti-NGF therapies. Regulatory agencies continue to evaluate these reports to better understand frequency, risk factors, and causality.

As with any newer targeted therapy, careful case selection, informed discussion with the veterinarian, and ongoing monitoring are important.

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2024-2026 Updates

In recent years, additional targeted therapies have expanded options for managing chronic itch and osteoarthritis pain in dogs. Newer JAK inhibitors and monoclonal antibody therapies continue to evolve, with some offering longer dosing intervals and more selective immune or nerve-pathway targeting. For osteoarthritis, extended-duration nerve growth factor (NGF) antibody therapies and localized joint interventions are under active study and clinical use in some regions.

As with all newer biologic and targeted treatments, ongoing post-approval surveillance continues to refine our understanding of both benefits and potential risks.

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A Multimodal Approach

Chronic itch and osteoarthritis pain are typically managed with individualized, multimodal treatment plans. Veterinarians often combine targeted medications with environmental management, weight control, physical therapy, skin barrier support, or dietary adjustments. Understanding the underlying nerve pathways helps guide more precise combinations rather than relying solely on generalized anti-inflammatory treatment.

In Closing

Dogs share many of the same itch and pain pathways as humans, so advances in this research are likely to benefit both species. As scientists better understand the nerve cells and signals involved in chronic itch, more targeted treatments may become available—improving comfort and quality of life for affected dogs.

Related articles:
Chronic Versus Acute Pain In Dogs: What Is The Difference?

Further reading:
The multiple pathways for itch and their interactions with pain