Guillermo Ceniza-Bordallo,1,* Eric Zimmermann,2,* Marie Vigouroux,2 Kacper Niburski,3 Maryse Fortin,4 Jean Ouellet,5– 7 Juan Pablo Cata,8,9 Pablo M Ingelmo2,7,10,11 1Department of Radiology, Rehabilitation and Physiotherapy, Faculty of Nursing, Physiotherapy, and Podiatry, University Complutense of Madrid, Madrid, Spain; 2Edwards Family Interdisciplinary Center for Complex Pain, Montreal Children’s Hospital, Montreal, QC, Canada; 3Department of Anesthesia, University of British Columbia, Vancouver, BC, Canada; 4Department of Health, Kinesiology & Applied Physiology, Concordia University, Montreal, QC, Canada; 5Department of Paediatric Surgery & Surgery, McGill University Health Centre, Montreal, QC, Canada; 6Department of Scoliosis & Spine Surgery, Shriner’s Hospital for Children, Montreal, QC, Canada; 7Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada; 8Department of Anesthesia and Perioperative Medicine, the University of Texas – MD Anderson Cancer Center, Houston, TX, USA; 9Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA; 10Department of Anesthesia. McGill University, Montreal, Canada; 11Research Institute, McGill University Health Center, Montreal, Canada*These authors contributed equally to this workCorrespondence: Guillermo Ceniza-Bordallo, Email gceniza@ucm.esAbstract: Space flights can produce physiological changes in the spine, leading to the development of acute and chronic pain in passengers. However, there is a lack of comprehensive literature exploring physiological spine changes and acute and chronic pain in space passengers (astronauts and animals). The first aim of this study was to identify the physiological changes experienced by passengers (humans and animals) after space flight. The second aim was to identify the incidence of low back pain during and after space flight. This systematic review was conducted following PRISMA guidelines and was pre-registered in PROSPERO (ID 451144). We included Randomized Controlled Trials or longitudinal studies in humans and animals, and the variables must be assessed either in-flight or post-flight. We conducted a literature search in major databases combining the keywords: Pain; Space; Low Back Pain; Astronauts; Spine Changes; Microgravity; Physiological Changes; Humans; Animals. Risk of bias and quality of studies were analyzed, and the level of evidence was assessed using the GRADE system. After duplicates were removed, 115 abstracts were screened by two reviewers, and finally, 11 articles were included in this review. The evidence indicates that astronauts experience muscle atrophy in the lumbar multifidus with a moderate to large effect, especially in the L4-L5 and L5-S1 segments. Space flights also decrease the range of motion with a moderate effect, along with disc herniations and disc dehydration. 77% of astronauts experience pain during spaceflight, and 47% develop acute pain after spaceflight. Chronic pain was reported by 33% of the astronauts. After space flights, astronauts suffer from lumbar muscle atrophy, reduced range of motion, disc herniations, and disc dehydration, with a high incidence of both acute and chronic pain.Plain Language Summary: Space travel affects the spine and can cause both immediate and long-term pain. Our study aimed to understand what changes happen in the spine during and after space travel and how often these changes lead to low back pain.Why was the study done?We wanted to investigate the specific spinal changes and the frequency of low back pain in both astronauts and animals exposed to space travel. This is important because understanding these effects can help improve health interventions for space travelers.What did the researchers do?We reviewed studies that examined spine changes and pain in humans and animals during and after space flights. We used a systematic approach to find relevant research, following strict guidelines and assessing the quality of each study.What did the researchers find?Astronauts often experience muscle loss in the lower back, particularly in the lumbar spine.Space travel reduces the spine’s range of motion.There is a significant occurrence of disc herniations and disc dehydration.77% of astronauts report pain during space flights.47% experience acute pain after returning to Earth.33% suffer from chronic pain post-mission.What do these results mean?Our findings show that space travel can lead to serious spinal issues and a high risk of pain. These results highlight the need for better health strategies to protect astronauts during and after their missions. Understanding these effects is crucial for developing effective interventions and ensuring the well-being of space travelers.Keywords: chronic low back pain, space flight, physiological changes, microgravity