Nociception by orthodontic tooth movement stimulate Trigeminal nerve free endings in periodontal ligament (PDL) , and neuropeptides such as substance P and CGRP are synthesized in Trigeminal ganglion sensory cells and released both centrally and peripherally around blood vessels in PDL and pulp. Neuropeptides such as CGRP and substance P are the signal transmitter of pain and might modulate vascular enlargement, blood flow or vascular permeability. CGRP receptor for its subunit, receptor activity modifying protein 1 (RAMP 1) distributed on osteoclasts and osteoblasts in PDL. CGRP may have effects on bone remodeling due to not only inhibiting bone resorption like calcitonin but also directly stimulating bone formation in the luxated PDL and during experimental tooth movement.