I can think of several uncomfortable enemas, starting with Fleet. I tried one out of curiosity when I was young and then several years ago had to have one to prep for a flex sig exam. With the last one, I felt like I was going to turn inside out - I've wondered if I'm allergic to the chemical used in a Fleets. If a Fleet E is ever ordered again, I'll ask for "the old fashioned kind."
Another unpleasant enema was given to me by a pro domme. It felt spicy hot with a mild burning sensation. She also used a little oil of wintergreen on my anus which also had a mild burning sensation. She assured me that the solution was safe and that she'd tell me later what was in it. That was followed by a rinse. I didn't have any bad side effects but I felt worn out by the end of the session and I neglected to ask her about the recipe for the enema solution. That was in 2015, and the last time I saw a pro domme.
I've also done volume tests, I'd guess about six times over several years. For each test, I had a phone girl coaching me thru it. We started with about three cleansing castile soap and water enemas with increasing volumes until I was mostly clear. This would be followed by warm saline solution and tracking the volume I took. The result was always around a gallon of solution. We were always careful to stop when it felt uncomfortable but not dangerously so. Feeling so full, I was not able to retain the solution for long. With such consistent results, I'm no longer doing volume tests.
I've also experimented with warm temperatures. I learned from reading and experience that my safe max temp is 110 F / 41+/- C. I tried warmer, like 115 or so. That wasn't uncomfortable but I was sweating. I've also learned "the hard way" how too much soap can cause a lot of discomfort and a prolonged "recovery" from the enema. I also found early in my enema experimenting that mineral oil resulted in prolonged and messy after-effects.
I've saved the best for last: I enjoy erotic discomfort and feeling at the mercy of a nurse or other authority figure. My favorite uncomfortable enema is plain cold water, refrigerator temp, around 38 F / 3 C, no ice. I like to do this with a phone girl who directs the opening and closing of the clamp while she counts to five or ten from start to stop. We do this multiple times and that way, I'm getting it in doses. Sometimes I'll expel soon after taking all of the cold water, about 1L+. Other times, with a smaller volume, she'll instruct me to hold the enema until I give her a semen sample. This started a few years ago when I had a phone enemate who introduced me to "chilly enemas." After we had shared dozens of calls together, we agreed to do mutual video play and take turns watching each other. Cold water enemas were so erotic for her that she would cum just from doing that... and she let me watch several times. How I miss her!