There are many forms of separation:

• Separation from things we associate with our identity: people, places, products or companies you build, Capital or wealth, objects, or ultimately death.
• Separation can be temporary or permanent.
• Separation could be due to your own doing or due to situations beyond your control.

When you deeply associate your existence and identity to things beyond your mind, they start owning a significant portion of your mind space and thus when remove create an intense feeling of lacking — a null, void, and emptiness. This in turn leads to suffering and sadness.

Footnotes:

• Dokkodo