Kristine Nielsen seems to come from sober parentage – her mother worked as an administrative assistant in Jimmy Carter’s White House and her father was a U.S. Navy captain. But the star of “Miss Witherspoon,” Christopher Durang’s lampoon on the afterlife currently playing at Playwrights Horizons, may be New York theater’s zaniest presence.

“Miss Witherspoon” marks the third time Ms. Nielsen has originated a part in a Durang play. The sort of manic energy she injects into a production can be communicated simply by the title of one of those plays, “Mrs. Bob Cratchit’s Wild Christmas Binge,” or the name of the character she played in another, “Betty’s Summer Vacation” – Mrs. Seizmagraff. As for the new play, she plays the title role, a recently deceased curmudgeon who is persistently reincarnated against her will until her “brown tweed aura” clears up a bit.

The actress and the playwright first became friends while acting in a play together. “We were in a bomb at Lincoln Center, ‘Ubu,’ which no one remembers and you can’t find the poster for – it’s behind some door at Lincoln Center. We had the same sensibility.” And what is that sensibility exactly? “Slightly cock-eyed. Slightly off.” She also credits their symbiosis to “the Nielsen family sense of humor.” “It’s so much easier and nicer to look at the world that way, than to take it all so much to heart. Otherwise, you’d be weeping all the time in the middle of the street.”

Their shared perspective allowed both of them to work on a scathing satire like “Betty’s Summer Vacation” – in which Mrs. Seizmagraff guzzles cocktails and spews Pollyannaish bromides while rape, murder, and mutilation take place behind the doors of her beach house – and consider the subject matter hilarious.

“I know I laughed out loud when I first read it and I know I was one of the few,” Ms. Nielsen remembered. “I think a lot of people were scared. It was shocking. It had a lot of things that people thought: ‘Oh, I don’t know if that’s funny.'” What is inarguable is that she, Mr. Durang, and director Nicholas Martin somehow made it funny; the play was a critical triumph in 1999 and won her an Obie Award and a Drama Desk nomination.

Those who have seen Ms. Nielsen on stage likely remember her as an entertaining blur. She is always in motion – springing in and out of chairs, eyes spinning, arms awhirl, feet skittering about. Her voice, meanwhile, is a cheerful-seeming singsong, but one from a disc with a couple hiccups on it and set at too fast a speed. The overriding effect is of a desperately bubbly, borderline suicidal hostess who knows her dinner party is sinking fast. (Which is actually a good description of her part in “Omnium Gatherum,” the fevered doomsday drama by Theresa Rebeck and Alexandra Gersten-Vassilaros, where she gave the audience a good idea how Martha Stewart might behave if hellfire was licking at her feet.)

“I mostly have done comedy. Yale” – as in the Yale School of Drama, which she attended followed undergraduate work at Northwestern University – “would smack me for ever saying I was limiting myself. But it’s more fun for me, more seductive. It’s a greater way of communicating. I enjoy it more than the sturm and drang and the tears. But that doesn’t mean it’s any less painful.”

Certainly there is a lot of pain for Miss Witherspoon, a nonbeliever who longs for the Jewish afterlife, described by Mr. Durang as a sort of ongoing general anesthesia, but is instead repeatedly rocketed back to miserable earth by a determined and maddeningly happy Indian spiritual guide. Witherspoon responds by downing drugs and taunting a vicious family dog – anything to get out of living another life. None of this discomforts the actress terribly much.

“I find this play devilishly funny,” she said, “but I always find a lot of true anxiety and pain about questions of faith, questions of how you fit in the world. I do think [Mr. Durang] appreciates that I find the pain in it, but I also like entertainment. I don’t want to scare anybody. I want the audience to hear it, to know what we’re thinking. I don’t want it to be grotesque or camp. I’d like to keep it on a truthful level, so you can understand what I’m saying, but not in such a way that I have to mug so much.” She paused a second and – in a very “Miss Witherspoon” manner – laughingly added: “But, then, everyone tells me my face is elastic, so I don’t know what I’m talking about. So good luck figuring it out!” No wonder she and Mr. Durang get along so well.