Abstract: AIM To investigate the effects of chronic neuropathic pain (CNP) on the function of myocardial mitochondria. METHODS Forty male C57 mice were used in the present study. Ten mice were used to establish chronic neuropathic pain model using chronic compression of dorsal root ganglion (CCD). Ten mice were regardedas control group (Con). Ten mice of one month were injected with AAV9-CMV-ALDH2 (3×1011 vg per mice) via vena caudalis. Ten mice of one month injected with AAV9-CMV-GFP via vena caudalis were regarded as the negative control. After 4 weeks, ALDH2 was over-expressed stably, and CCD model was established (CCD+ALDH2). After 3 weeks of CCD, the myocardial tissues were extracted. Detected the levels of reactive oxygen species (ROS), malondialdehyde (MDA), the activity and acetylation of MnSOD, and the activity and carbonylation of SIRT3. RESULTS CNP dramatically increased mitochondrial oxidative stress and lipid peroxidation, and decreased mitochondrial membrane potential in mice myocardium. The acetylation of MnSOD increased significantly in CNP mice (P<0.05), leading to the decreased activity (P<0.05). The results mentioned above suggested that CNP triggered mitochondrial dysfunction in the myocardium. Furthermore, the serum level of 4-hydroxynonenal (4-HNE) increased markedly (P<0.05), resulting in the carbonylation of SIRT3. The up-regulation of ALDH2 significantly attenuated CNP-induced carbonyl stress and pain (P<0.05), and maintained mitochondrial function. CONCLUSION CNP induces myocardial carbonyl stress and mitochondrial dysfunction. The up-regulation of ALDH2 effectively mitigates pain and myocardial mitochondrial dysfunction.