Osteoarthritis (OA) of the hand is a major cause of pain and functional limitation, central sensitization of pain can be one of the causes: this hypothesis opens avenues for research in the modulation of pain pathways. The peripherally directed therapies may modulate pain perception bilaterally. This hypothesis opens avenues for future research in the modulation of pain pathways, perhaps offering targets to optimize peripheral manual and physical therapies for pain management in hand OA.