Pain sensation induced by kidney stone (renal calculi) in ureter, a kind of visceral ducts connecting the kidneys and bladder, critically depends upon the relative size of stone to ureter. To quantify such pain sensation, we draw a parallel analogy between the mechanisms underlying skin pain (which can be quantified with a holistic pain model consisting of a modified Hodgkin–Huxley model and gate control theory) and mechanism of ureteral pain to extend the holistic pain model to the stone-blocked ureter. We then perform finite element simulations to obtain key mechanical stresses on the ureter wall exerted by a kidney stone having varying sizes. These stresses are subsequently adopted to calculate the voltage potential of neuron membrane in the holistic pain model and eventually a theoretical framework to quantify the dependence of ureteral pain sensation on stone size is established, for the first time. We demonstrate that ureter pain sensation increases sharply when the diameter of the kidney stone becomes 7.5% to 20% larger than the inner diameter of ureter, peaking at ∼20% larger; however, increasing further the stone diameter leads only to marginally exacerbated pain sensation. Other related effects on ureter pain sensation, such as ureter wall thickness, ureter stiffness, and intra-abdominal pressure (IAP), are evaluated. The results of the present study provide insightful information for urologists to diagnose and treat patients with renal calculi in a more personalized way.