How stress can cause Pandora syndrome in cats

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Feline lower urinary tract disease, also known as feline interstitial or idiopathic cystitis (FIC), is more than just a primary bladder disease, according to a lecture presented at the Fetch Kansas City in Kansas City, Missouri.¹ Now referred to as Pandora syndrome, the term encompasses felines that are experiencing chronic lower urinary tract disease symptoms, but do not have urinary tract infections, crystalluria, or uroliths. Pandora syndrome is a systemic disease that includes cats that have recurring clinical episodes along with other underlying health problems.

In her lecture, Lisa Restine, DVM, DABVP (feline), associate feline professional veterinary affairs manager at Hill’s Pet Nutrition, talked about the link between stress and Pandora syndrome in cats.¹

“We still use [the term] FIC today to talk about this [condition], but what we're kind of trying to lean more into is Pandora syndrome, and this is the most recent term that has been coined…. The goal behind this name change is to recognize that this is not a primary bladder disease. This is a systemic disease that affects the bladder, but there's other things that are occurring as well that are linked. And we want to think about that big picture instead of just thinking about this as a bladder problem,” explained Restine in her lecture.¹ “Hopefully that will help guide our treatment,” she added.

Cats, stress, and Pandora syndrome

Stressors are events that occur internal and external to the body that activate the central threat response system (CTRS), also known as the central stress response system (CSRS). According to Restine, Pandora syndrome arises from continuous stress, and therefore constant activation of the CTRS. As a result, the CTRS becomes hypersensitized, which triggers changes in the endocrine, autonomic nervous, and immune systems. This leads to the development of disease in one or more organ systems, or Pandora syndrome.

In felines with chronic stress, the hypothalamic-pituary-adrenal (HPA) axis, which is responsible for the stress response, can become dysfunctional. “Persistent stress will lead to the hypersensitization of [the CTRS], and what [researchers] found in these cats is [that] there's actually a change within their brain on how they process stress,” explained Restine.

Stress can be categorized into various types, including acute stress, which is brief and temporary; and chronic stress, which persists over a longer period. Additionally, stress can be positive, arising from enjoyable experiences; or negative, which causes negative emotions.

During her session, Restine informed attendees of some signs of stress. “What happens with cats if they're having a lot of mental health issues [due to] stress, it's hard to quantify, but these cats might be scratching a lot, they are more aggressive, both at home or in a veterinary clinic, or they're experiencing self-mutilation, overgrooming, barbering, or they're inappropriately eating—either over or under eating,” she said. “Those [behaviors lead] to physical problems because of that kind of stress.”

Other cats may exhibit social-related responses, like hiding, freezing, fidgeting, or fleeing, according to Restine. Additionally, chronic bacterial infections or flare ups can be indicators of stress, as well urinating outside the box and chronic sneezing.

“Our signs are pretty self-explanatory. They are the lower urinary tract signs that we see, but the key, the key is that they last…This is not just something [where the] cat is going to have urinary issues all the time. And a lot of times, what happens is [the cat] may have an FIC flare up, [urinate] outside of the box for a few days, and be fine for 3 or 4 months. And [then the cat will] do the same thing [again], and that owner might not even get to your clinic because they don't even think it's a problem,” explained Restine.

“So that's something you want to ask [the client] about and make sure that you're paying attention to. You want to look for these comorbidities. Look for vomiting. Look for hairballs. Look for alopecia. Is this cat this licking its belly a lot…? Is it a chronic sneezer…? And…do the signs go away if they change the environment?” Restine continued.

Can stress also affect embryos?

Although a cat’s environment may contribute to or be the cause of its stress, some cats are predisposed to systemic changes before birth. Restine explained that research on cats and humans shows that significant stress experienced by a mother during pregnancy can impact fetal development. In essence, chronic or extreme stress before birth or in early life can lead to changes that can also make cats more susceptible to Pandora syndrome later on.

Diagnosing Pandora syndrome

Pandora syndrome is a diagnosis of exclusion, according to Restine. Diagnosing this condition requires ruling out other causes of urinary issues. In her session, Restine explained that the diagnosis procedure involves imaging of blood and urine analysis for patients with bladder issues. Moreover, ultrasounds and x-rays can be conducted. Restine also emphasized doing a manual sediment to ensure visibility of potential crystals under the microscope. Blood work may also be carried out.

It is also important to gather complete background information about the cat. This includes factors like the cat’s pre-adoption history and medical history, habits, routine, eating patterns, and more.

Managing the disease

“This is a self-limiting disease,” said Restine of Pandora’s syndrome. As such, treating felines with Pandora syndrome primarily consists of controlling pain and decreasing recurrence.

Restine cautioned against the use of antibiotics, explaining that an overuse of these medications could hurt the cat’s microbiome and create side effects. “What you have to remember is every pill, when you are giving [it to] a cat, is a stressful event. And now you're saying, ‘here are 3 medications to give this cat’—you are now creating stressful events at home for 3 to 5 days,” emphasized Restine.

To manage the disease, Restine explained that increasing moisture intake is the “proven management.” However, it “is not just about adding more water sources,” Restine said. “A canned diet is key, and making sure that they have a lot of access to water as well, but adding extra water to that food is helpful too.”

“Another interesting thing about cats, about that moisture content, is that [what] cats…actually like more…is the novelty of having a new water source, so it's actually more beneficial to move the same water sources around the house and keep them new and exciting, to increase the amount that they're drinking,” Restine explained.

The last key component of Pandora syndrome management is providing a stress-reducing environment. This includes reducing stress at hospitals where a cat might be spending time. This can be done by providing the cat with blankets with bedding from their home and places to hide or sit on top of, as well as maintaining a routine.

Reference

Restine L. Opening pandora’s box: Feline idiopathic cystitis – it’s more than just the bladder. Presented at: Fetch dvm360 Conference; August 23-25, 2024; Kansas City, MO.