John Brown caught a 19-yard pass on the second play of the game Sunday. But his seemingly big day never developed, Smoke later went to the sideline with hamstring issues, and the Cardinals sit here, with five games left in this season, wondering about the long-term abilities of a wide receiver who has already shown he was an important part of the offense.

To see Bruce Arians basically at a loss when asked about where Brown -- dealing with a sickle-cell issue -- goes from here has to be a concern. The Cardinals and Brown continue to seek a remedy that will get Brown back to where he should be -- this is a genetic issue, after all, so you'd think after two solid NFL seasons and one 1,000-yard effort, there is a way to have this work out.

But as quarterback Carson Palmer said, Brown's 2016 problems -- which include the concussion that knocked him out of the preseason and set him back -- have been a "big, big loss." You can see it when Brown does play. He so easily got open much of the season last year. That separation is absent this year, either down the field or on the deeper crossing routes at which he's been so good. Many pointed out Brown's inability to chase down Vikings cornerback Xavier Rhodes on Rhodes' 100-yard interception return as a red flag. That's hard to argue.

The inexplicable season of Michael Floyd has hurt, but I would argue that Brown's absence has been the most painful. It was Brown's routes that most impactfully opened up spots for Larry Fitzgerald. Whether or not Brown can find his way back to full Smoke status this season, this coming offseason could be crucial in finding out what this problem could mean long-term.

"It's been a tough year, away from football," Palmer said of Brown. "Trying to figure out what his workload is in the week and what his workload is on Sundays, how to stop what happened last Sunday from happening again. He's in the learning process trying to figure it out. You can just pray for him and be there for him and do whatever you can for him."