This study was to observe the changes in the expression of calcium homeostasis modulator 1 in trigeminal nucleus of trigeminal neuralgia rats with the infraorbital nerve-chronic constrictive nerve injury and to explore the role of calcium homeostasis modulator 1 in trigeminal neuralgia. Thirty Sprague Dawley rats were randomly assigned to 5 groups, control group, sham group, infraorbital nerve-chronic constrictive nerve injury group, ruthenium red group and normal saline group, with 6 rats in each group. All experimental rats were tested for pain behavior 1 d before surgery, 1, 3, 5, 7, 9, 11 and 14 d after surgery, including the mechanical pain threshold of Von Frey filament in the trigeminal innervated skin area and number of faces captured in video recording. The expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus was detected on d 15 after surgery in all experimental groups. The expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus of the infraorbital nerve-chronic constrictive nerve injury group was significantly higher than that of the control and the sham group on the 3rd and 15th d after modeling. Intraperitoneal injection of ruthenium red, a calcium homeostasis modulator 1 inhibitor, increased the mechanical pain threshold of infraorbital nerve-chronic constrictive nerve injury rats and significantly reduced the number of scratches, but did not change the expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus. In conclusion, the expression of calcium homeostasis modulator 1 protein in the trigeminal spinal nucleus is involved in the central sensitization of trigeminal neuralgia pain. Moreover, the hyperalgesia can be improved by using calcium homeostasis modulator 1 inhibitor without affecting the calcium homeostasis modulator 1 expression.