Pandora Syndrome in Cats: Causes, Symptoms, and Treatment

Kirsten McCarthy / Cats.com

Pandora Syndrome is a complex disorder associated with stress and anxiety in cats. It commonly involves inappropriate urinary behavior but may include many other signs and symptoms too.

In this article, we’ll review where the term Pandora Syndrome comes from, what the disorder involves, and strategies you can use at home to alleviate its effects in your cat.

What Is Pandora Syndrome?

Pandora Syndrome is a large encompassing disorder of stress and anxiety seen in cats. As a syndrome, it comprises a variety of clinical signs and symptoms and is not a singular disease of one organ or system.

The term itself was coined by Dr. Tony Buffington from Ohio State University. In cooperation with other colleagues from OSU, the group developed their theories for Pandora Syndrome while investigating a large study group of cats with feline lower urinary tract disease (FLUTD), which is also called feline urologic syndrome (FUS).

In cats without urinary tract infection, bladder stones, or other physical causes that contribute to FLUTD and FUS, remaining cats have feline idiopathic cystitis (FIC). This is a sterile (non-infected) bladder inflammation of an unknown cause, but thought to be related to stress.

The OSU researchers discovered in their study that many of the cats with FIC also had some other things in common. Many had other health issues in their past, even going back to their earliest years. Many had inconsistent or unstable home environments, being orphaned, abandoned, rescued strays, or in overpopulated environments. Most also had significant improvement in their symptoms when placed into an enriched environment during the study.

This led to the conclusion FIC in cats was not caused by a specific bladder disease, but instead by some other disease of the body affecting the bladder secondarily.

This appeared to mirror a similar condition in people called interstitial cystitis, where patients have additional health history abnormalities that collectively have terms like “bodily distress syndrome” or “central sensitivity syndrome”.

As a condition with many underlying causes and components, the term for Pandora Syndrome is derived from the many complex problems that are released from the mythical box that the character Pandora opens in Greek mythology.

At its core, Pandora Syndrome is an anxiopathy. An anxiopathy is a term coined to describe a state of disease induced by a chronic perception of threat.

The part of the body responsible for helping an individual cope with stress and anxiety is called the central stress response system (CSRS).

The CSRS is situated in the brain and is part of the hypothalamic-pituitary-adrenocortical axis. Essentially, this stress response is managed by a combination of hormones and neurologic responses.

Most are familiar with fight or flight response in animals. In response to danger or life-threatening situations, the body will induce this response, which involves an increased heart rate, pupil dilation, increased blood sugar and blood flow to the muscles, and other responses. Rational thought and decision making is replaced with reaction. Once the threat is gone, the body’s responses return to normal.

With chronic stress, if the CSRS is chronically activated, it can become overworked, leading to problems with hormone signaling, the nervous system, and the immune system.

For chronic stress to be present, there only has to be the perception of a threat (whether one truly exists or not) and the perception of poor control or dominance over the threat.

In cats where this occurs, changes can happen not just in the urinary tract but other body systems as well including the respiratory tract, gastrointestinal tract, and the skin.

Causes of Pandora Syndrome in Cats

At its core, Pandora Syndrome is caused by chronic activation of the central stress response system (CSRS), leading to multiple physiological effects on the body.

These causes often occur very early in life, even prior to birth. For example, if a cat’s mother was exposed to environmental stressors while they were in utero, this stress can affect the kittens. A severe enough stressor at any time in life can also lead to the syndrome.

There are some common life stressors that have been found to contribute to cats developing Pandora Syndrome. These may include but are not limited to:

• Affected kittens being orphaned/weaned early from their mom
• Early weaning or abandonment leading to the need for bottle feeding
• Poor nutrition/malnutrition
• Food/resource competition (either in multi-cat households or colonies)
• Competition for litter boxes
• Competition for safe spaces, quiet places, etc.
• Rehoming/inconsistent home environment
• Poor environmental stimulation/enrichment
• Another chronic physical disease affecting health
• Another cat in the home affected by a chronic disease or stress
• Abuse or neglect
• Chronic pain or discomfort

It’s important to understand that many cats may be able to adapt to and cope with stressors in their lives of one kind or another.

But in cats with Pandora Syndrome, in addition to one or more stressors being present in their lives, they also have an innate inability to cope with this stress normally. This has led to Pandora Syndrome also being called a maladaptive stress disorder, where a cat perhaps genetically is incapable of responding to one or more stressors in the same way as another cat. Some refer to this as a cat being “wired” poorly to respond to stress.

It is also possible for one stressor to be so severe (such as a cat living in a stable home for a long time suddenly being abandoned) that Pandora Syndrome may develop.

Symptoms of Pandora Syndrome in Cats

Pandora Syndrome is often described as a urinary tract disorder. It’s true that it was originally investigated as part of a study in cats with lower urinary tract disease and that FIC is a very common condition seen in cats with Pandora Syndrome.

But in cats with the disorder, other body systems can be affected, leading to other signs of illness as well.

In his article on the topic, Dr. Buffington lists the following as signs that may be seen in cats with Pandora Syndrome and the body system they affect.

• Behavioral: hiding, pica (chewing/eating inedible objects), aggression, periuria (urinating outside the litterbox), perichezia (defecating outside of the litterbox)
• Cardiovascular: hypertrophic cardiomyopathy, saddlethrombus (feline aortic thromboembolism or FATE)
• Endocrine: obesity, type 2 diabetes mellitus
• Gastrointestinal: odontoclastic resorptive lesions (FORLs), regurgitation, vomiting, hairballs, large bowel diarrhea, perichezia
• Immune: upper respiratory infections
• Nutritional: obesity, finicky eating
• Skin: overgrooming/barbering, chin acne, atopic dermatitis (skin allergies), behavioral ulcerative dermatitis
• Urinary: urinary bladder stones, interstitial/idiopathic cystitis (FIC), periuria, chronic kidney disease

It’s important to keep in mind that Pandora Syndrome is not exclusively associated with these conditions and they can have their own separate causes. For example, HCM in certain breeds of cats (like Maine Coons) has been linked to a specific genetic mutation.

Symptoms in cats with Pandora Syndrome may wax and wane. This is a common finding and considered an important criteria for considering Pandora Syndrome. For example, inappropriate urination may consist of a cat who urinates outside of the litter box for a few days, and then doesn’t do it again for a couple of months. The same may occur with diarrhea or defecating outside of the box.

These changes may be associated with known stressors (moving to a new home, a new pet being introduced, a large “disruptive” party at the house, construction nearby, etc.). But sometimes, the stressors are much less clear and the waxing/waning signs may even go unnoticed by cat owners at home.

If the stressors are constant, cat parents may then identify the issue as a recurring or consistent problem. This might be a cat urinating all over the house, not eating their food consistently, having chronic diarrhea, having hair loss or skin lesions, or whatever it may be.

Diagnosis of Pandora Syndrome

Pandora Syndrome is considered a diagnosis of exclusion. As a syndrome that can encompass many separate signs of illness, there is no specific test to diagnose it.

If your cat has signs of illness, like inappropriate urination, your vet will perform appropriate testing to look for other common disorders that can be ruled out. In the example of inappropriate urination, this would include a urinalysis to check for infection and urinary crystals, bloodwork to check for underlying disorders that cause urinary changes (like kidney disease or diabetes), checking for bladder stones with an x-ray or ultrasound, and ruling out a bladder tumor with ultrasound.

In his article on the topic, Dr. Buffington includes some inclusion and exclusion criteria to help narrow down if Pandora Syndrome may be present:

Exclusion Criteria (Pandora Syndrome is Less Likely)

• Other diagnosable causes of signs
• Incompatible history, physical exam findings, labwork, imaging, etc.
• Explainable peripheral pathology

Inclusion Criteria (Pandora Syndrome May Be Involved)

• An adverse experience in life, especially early on
• Comorbidity, sickness behaviors
• Waxing and waning signs (especially in relation to environmental changes or events)
• Global (complete) response to Multimodal Environmental MOdification (MEMO)

We’ll discuss the important components of multimodal environmental modification (MEMO) shortly, but a cats’ response to MEMO can also act as a diagnostic tool to see if Pandora Syndrome is present. As Dr. Buffington noted during the OSU study, nearly all the cats involved (about 200) showed great improvement or resolution of their symptoms when environmental enrichment modifications were made.

One last consideration is whether a cat’s signs of illness are disproportionately severe compared to the physical state of disease that’s found. Dr. Buffington uses the example of people with ulcerative colitis having symptoms proportional to the degree of their disease, but people with irritable bowel syndrome often having no physical bowel pathology while having severe symptoms.

In the case of a cat, this could look like a cat with chronic diarrhea with no infectious agents found, and no bowel thickening or lymph node enlargement to support inflammatory bowel disease and poor response to dietary therapy.

A key part of diagnosing Pandora Syndrome is a very detailed history. This is especially important for multi-cat households where detailed information for other cats in the home can be just as important. Illness and behaviors in other cats in the home may be contributing as stressors.

Questions your vet may ask and/or things that are important to relay include:

• Life history if known (stray, bottle fed as a kitten, shelter adoption, relocation)
• History of previous illness, trauma, or environmental instability
• Any health history involving multiple problems, especially that wax and wane
• Any perceived association with health problems and environmental stressors
• Number and location of litter boxes in the home
• Number and location of other resources (food, water, hiding places, toys, etc.)
• Other pets in the home
• Illnesses or conditions other pets in the home may have
• Activity/play/socialization time
• The presence of environmental enrichment items (scratching posts, window perches)

Treatments for Pandora Syndrome

Providing an enriched environment for your cat is one approach to treating pandora syndrome. Mel Grin / cats.com

There isn’t one single treatment for Pandora Syndrome, since it can encompass multiple signs of illness.

For secondary illnesses related to Pandora Syndrome, the most appropriate medications for those conditions will still be used. For example, a cat with hypertension (high blood pressure) will still need blood pressure medication. A cat with chronic pain will still need pain medication.

Some cats may have illness so severe that they even require hospitalization. An example is a cat with FIC that develops a urethral obstruction.

But when treating the entire syndrome as a whole, cats will respond to multimodal environmental modification (MEMO).

Here are the components of MEMO as described by Dr. Buffington.

1. Space

Every cat needs their safe space. You may notice that your cat prefers certain locations. In multi cat homes, you may notice that each cat has their own place they prefer. For example, I know my cat Annie prefers the grey cat bed on the lounge chair in the basement, the cat tunnel in the dining room, and one of the kids’ beds with all the stuffies on it. Her brother Bart prefers our bed upstairs. When he’s scared, he prefers a spot in the corner of our closet.

Cats also interact with physical structures in their home. They need places to scratch and rub on. Providing both horizontal and vertical scratching surfaces can be important, even if you think your cat has a preference.

If your cat scratches your furniture, try to find a way to either provide a close by source that’s preferred, like a cat tree, or use a cat scratch guard. I found our cats preferred to scratch vertically on the corners of our couch, leading me to get a dual furniture protector and scratching post to both protect the couch and provide Annie and Bart with approved places to scratch away.

Cats are very motivated by smell. Using scents in the home like catnip, silver vine, or valerian can provide a sense of calm. Feliway contains valerian and is one safe and effective way to provide a calming effect through the plug-diffuser or spray.

2. Food

Cats need a safe and quiet place to enjoy their meal. They shouldn’t be surprised or startled by other animals, people, or appliances while they’re trying to eat. While the kitchen is a common location to include food and water bowls, if this is a high traffic and busy area, a quieter place like a bedroom or spare bathroom might be more suitable.

Cats do have their preferences with some preferring wet/moist food and others preferring dry food. Be careful of any abrupt changes in their food, including even the texture or shape. When possible, introduce a new food alongside the current food to gauge your cat’s interest in it and prevent a hunger strike.

Cats are instinctual hunters. Many think of them as lazy, sleeping for 16-18 hours a day. But in reality they rest to prepare for quick and intense hunting in short bursts. It’s important to try to emulate this in the home environment too. Providing puzzle bowls that require some intellect can help slow down eating and provide stimulation. You can also hide high-value treats around the house using something as simple as a toilet paper roll or a product like The Hunting Snacker by Doc and Phoebe’s Cat Co.

3. Play

In addition to hunting behaviors, cats also benefit from play and social interaction. This might be active play with humans in the home, or leaving favorite toys out that they can play with at their discretion. At 16 years, both of my cats still have a play preference for small stuffed mice.

Instead of play, some cats may prefer cuddling, petting, and grooming as their social outlet.

4. Conflict

When a cat feels threatened, they will respond by trying to restore their perception of control over the situation. But this can look different for different cats. Some may become aggressive, others may withdraw and hide, still others may develop signs of illness.

Conflict is especially important in multicat households. It’s important to realize that this will not always look like outright hissing, growling, or fighting. Other signs of conflict may include avoidance of certain parts of the house, reluctance to come out to eat or use a certain litter box.

Conflict among cats can arise from multiple sources including:

• A perception of a threat to their status in the home
• Access to high value resources
• Access to scarce resources
• Access to favorite locations
• Perceived threats due to illness in other pets in the home
• The presence of “visiting” cats outside the home (causing displaced aggression in the home among the indoor cats)

As Dr. Buffington describes, providing a “house of plenty” may greatly reduce Pandora Syndrome’s impact on affected cats.

Cat Care Tips

Implement multimodal environmental modification (MEMO) with one additional litter box per number of cats in the home. Apply the same rule for other values resources too. Emma  Williams / cats.com

Multimodal Environmental MOdification (MEMO) is the core approach to helping cats with Pandora Syndrome. A positive response to MEMO approaches is considered very supportive or even confirmatory of the condition. If you notice signs of illness that come and go, especially urinary signs, consider employing as many MEMO approaches as possible.

Here are some tips to employ MEMO in your home.

• Follow the 1 + 1 rule for all valued resources. This means having one for each cat plus one additional. This rule applies to litter boxes, water bowls, toys, and safe spaces.
• Cats are natural water seekers. Rotate at least one water bowl to different locations around the home to add extra environmental enrichment.
• Other forms of environmental enrichment include additional scratching posts, toys, and window perches.
• If your cat is showing signs of medical illness associated with Pandora Syndrome (inappropriate urination, skin conditions, digestive upset) make sure to consult your veterinarian. These illnesses can occur independent from Pandora Syndrome but even if related, will require separate medical treatment.

Prevention of Pandora Syndrome in Cats

It’s important to remember that it may not be possible to fully prevent Pandora Syndrome. Cats can be affected while still in the womb if their mom was exposed to environmental stressors while pregnant with them. In these cases, a cat may already be poorly “wired” for stress even before they come into your care.

But it is possible to prevent flare-ups of illness associated with Pandora Syndrome primarily through focusing on multimodal environmental modification (MEMO). Maintaining a consistently enriching environment where a cat can be positively stimulated but still feel safe, independent, and have access to resources has shown to be key to quieting down Pandora Syndrome signs.