Bloodline Synergy
Bloodline Refinement is painful...
Usually, it's the most painful during the start and the finish, a person can develop some sort of resistance against it during the mid-refinement stages but at the final stages, the pain will escalate all over again.
This is due to the process of re-writing the physiology of a person to correct it according to the requirements of the bloodline they're integrating into their system. In the awakening stage of Bloodline Refinement, a person would usually rouse the slumbering potential of the bloodline deep in their bodies to activity. This will provoke the initial changes in a person which are undoubtedly caused by the bloodline itself.
As the refinement went on and bloodline purity and density become purer, the more intense its effects are, and at the final stages of the refinement, the pain increases because the body is now making these changes permanent and deeply seated into their genetics.