Introduction

Space flight’s implications for the human body are beginning to be understood. The space flights environment disrupts the homeostatic balance of many physiological systems, which are adapted to Earth.^1–3 Exposure to microgravity leads to a reduction in disc compressive loading, loss of spinal curvature, and lengthening of the vertebral column.^2,4,5

The risk of post-space flight disc herniation in the lumbar spine is three times higher compared to those not exposed to microgravity.⁶ The microgravity environment decreases physical demand on the body.^1,3,7,8 In 21 days, this results in a reduction in muscle mass of up to 40% and increased bone resorption markers in as few as 10 to 14 days.^1,3 Additionally, microgravity induces symptoms akin to aging, such as decreased cardiovascular capacity and immune dysfunction.^7,8 Preliminary data indicate that spinal stiffness persist for between 3 months to 1 year after flight.^6,9

Astronauts experience episodes of low back pain (LBP) during space flight with over half reporting moderate to severe pain intensity.¹⁰ This pain has been found to impact the quality of sleep, concentration, and the psychological and emotional state of astronauts, as highlighted in a previous review.^5,11 Moreover, after returning to Earth, nearly 70% of astronauts LBP within the first 3 to 10 days.^10,12 Additionally, 40% continue suffering chronic LBP up to one year after the flight¹ significantly affects the activities of daily living in post-space flight passengers, limiting their ability to perform basic tasks such as walking, bending, and lifting, which can hinder their post-flight rehabilitation and return to normal activities.¹³

Pain during space missions can hinder astronaut performance and jeopardize mission success.¹⁴ Therefore, understanding why it occurs and how to control pain during flight has been identified as a priority for space agencies.¹⁴

Despite advances, research in this area faces significant challenges due to the complexity of the space environment. There is a critical need to understand better the physiological changes that occur in the low back of astronauts during and after flights, and their potential relationship with the onset of pain. The first aim of this systematic review was to identify the physiological changes in the low back experienced by passengers (humans and animals) during and after space flight. Secondly, we aimed to identify the incidence of LBP during and after space flight in astronauts.

Materials and Methods

This systematic review was conducted following The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.^15,16 The review protocol was pre-registered in PROSPERO database (ID 451144).

Search Strategy

Two researchers (E.Z & G.C.B) searched in MEDLine, EMBASE, Global Health, PubMed, Web Of Science, Scopus, Cochrane Library articles published between January 1^st of 2010 January 31^th of 2024. The last search in these databases was carried out on February 1^st, 2024. The search strategy used the combined keywords: Pain; Space; Low Back Pain; Astronauts; Spine changes; Microgravity; Physiological Changes; Humans; Animals.

Selection Criteria

Type of Article

We include Clinical trials and longitudinal cohort studies (retrospective and prospective). We excluded narrative reviews, conference abstracts, opinion reports.

Type of Population

We include samples of humans or animals who were exposed to space flight, without restriction on the duration of exposure. The population includes astronauts, cosmonauts, participants in manned space missions, and animals used in space experiments. There were no restrictions on gender, age, or country of the human subjects. For animal studies, different species were included as long as the results are relevant and applicable to human health. We excluded studies that analyze only other environments of microgravity, such as bed rest studies.

Types of Outcomes Assessed

We included articles that evaluated physiological changes in the lower back, such as muscle atrophy, water content in spinal structures, changes in ligament density, structural alterations in the spine such as kyphosis or hernias, and other changes like disc degeneration and decreased bone mass. We also included studies that reported pain evaluation in passengers, using pain assessment methods such as pain scales, pain questionnaires, and clinical evaluations.

We excluded articles that did not distinguish between physiological changes in the lower back and those in other parts of the body.

Study Selection

Two reviewers (G.C.B and E.Z.) initially screened titles and abstracts from the search results, categorizing each as “excluded” or “potentially eligible” for our systematic review using Rayan software.¹⁷ Throughout this process, interrater reliability was consistently monitored by having both reviewers independently assess the same ten randomly selected sets of 115 abstracts. Interrater reliability was measured using Cohen’s Kappa.^18,19 Discrepancies between the two reviewers were resolved through discussion, with mediation of the senior author (P.I). Subsequently, the same two reviewers independently assessed the eligibility of 20 full-text articles randomly selected from the potentially eligible studies for the systematic review. Interrater reliability at this stage was again measured using Cohen’s Kappa.^18,19 Reviewers were not blinded to authors’ names, institutions, or journal titles. The remaining full-text articles were assessed by one of the reviewers (G.C.B. or E.Z). Any study that did not clearly meet the eligibility criteria was discussed and mediated by the senior author (P.I.) if needed.

Data Extraction

Two reviewers (G.C.B. and E.Z.) independently extracted data from all the articles included. Then the information extracted were checked by a second reviewer (P.I). The following data were extracted into a excel document: 1) Article characteristics: a) Country of the article; b) Type of study; c) Sample characteristics d) Flight duration, 2) Studies characteristics and spaceflight assessment, 3) Low back physiological changes, 4) Acute and chronic pain reports.

Methodological Quality Assessment

Risk of Bias

The risk of bias in each included study was assessed according to systematic review guidelines.^15,16 Risk of bias was evaluated using each specific tool by two independent reviewers (E.Z. and G.C.B). Disagreements or discrepancies were resolved by the senior author (P.I). Cohen’s Kappa^18,19 was calculated for both evaluations, considering the number of identical ratings between the two reviewers and the number of different ratings between the two reviewers in each domain of risk of bias and study quality.

For animal studies, the widely employed scale Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool was used.²⁰ The SYRCLES²⁰ assesses risk of bias in ten items, taking into account allocation sequence, distribution of participants’ baseline characteristics, randomized allocation and outcomes evaluation, blinded evaluation, and problems in study design. Each item is evaluated with three options: “yes”, “no”, and “unclear”.

For human studies, the Quality of Prognostics Studies Tool (QUIPS Tool),²¹ which assesses risk of bias in prognostic observational studies, was used. The outcomes were: 1) Spine impairments 2) LBP and the prognostics factors all covariables described before. The QUIPS Tool²¹ assesses the risk of bias in observational studies using six points: 1) Study participation, 2) Study attrition 3) Prognostic factor measurement 4) Outcome measurement 5) Study Confounding 6) Statistical Analysis and Reporting. For each point, it evaluates with three possibilities, “low”, “moderate” or “high” risk of bias introduced into potential prognostic factor and outcome.

Quality of Studies

Study quality was evaluated using each specific tool by two independent reviewers (E.Z. and G.C.B). Disagreements or discrepancies were resolved by the senior author (P.I). Cohen’s Kappa^18,19 was calculated in both evaluations, considering the number of equal ratings between the two reviewers and the number of different ratings between the two reviewers in each domain of quality of studies.

For animal studies, the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies Tool (CAMARADES tool),²² a scale used for these types of articles was used. The CAMARADES tool assesses the quality of studies according to ten items. Among these items, we excluded items 3, 6, and 7 because they did not apply to our included studies. Each item is sorted into three categories: “yes”, “no”, and “unclear”.

For human studies, the National Institute of Health (NIH) Quality Assessment Tool²³ is widely used to assess study quality as it allows for different study designs to be assessed.^23,24 The NIH Quality Assessment Tool²³ assesses quality of studies taking into account problems in study design, and focusing on internal validity. Each item is evaluated with three possibilities: “yes” “no” or “other” (CD, cannot determine; NA, not applicable; NR, not reported)”.

Data Synthesis

The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.^25,26 For each domain, the following were analyzed: (1) phase of the research; (2) limitations of the study (3) inconsistency of the results, (4) indirectness (not generalizable), (5) imprecision (insufficient data) and (6) publication bias, (7) effect size and (8) dose effect. We used the guidelines provided by Huguet et al,²⁶ the evidence was classified as high (++++), moderate (+++), low (++), and very low (+).

The assessment of all GRADE^25,26 factors was pilot-tested by two reviewers (G.C.B. and E.Z.) on 30% of the outcomes included in this review. Since the level of agreement was deemed to be adequate, one reviewer (E.Z.) assessed the evidence for the remaining outcomes, except for “Study limitations”. Any uncertainties were discussed by another reviewer (G.C.B). The “Study limitations” factor was independently assessed by two reviewers (G.C.B. and E.Z. or P.I.) using the QUIPS.²¹ Interrater reliability for the QUIPS Tool²¹ study limitations rating was evaluated using Cohen’s Kappa.^18,19

Quantitative Analysis

A meta-analysis was conducted to analyze the incidence of pain during and after spaceflight using statistical software Jamovi version 2.3.²⁷ There is not a minimum number of articles required to perform a meta-analysis; therefore, we included at least two articles to examine associations.^28,29 Sample sizes and the number of astronauts experiencing pain were selected and extracted from studies included in the analysis. Due to expected heterogeneity among studies, a random-effects model was applied.^30,31 This approach is appropriate for handling variability among studies and provides more accurate estimates when the approximate normal within-study likelihoods are replaced with the appropriate exact likelihoods, leading to a generalized linear mixed model.³² This is especially useful in the context of sparse and heterogeneous data, ensuring that differences among studies are adequately addressed.³²

The presence of heterogeneity among studies was assessed by Cochran’s Q statistic.³³ Additionally, the I² index was calculated as a measure of the proportion of total variability across studies due to heterogeneity rather than chance.³⁴ I² values of 75% or higher indicate a high degree of heterogeneity, reflecting significant variability among the results of included studies.³⁴ Because we expected a low number of studies, we also incorporated Tau and tau squared.³⁵ Tau and tau squared were calculated as estimates of heterogeneity among studies, providing a measure of variability among studies beyond what is expected by chance.^35,36 Higher values of tau and tau squared indicate greater heterogeneity among studies, suggesting that observed differences among studies are not solely due to chance but to real variations in the effects of the included studies.^35,36

Publication bias was evaluated using funnel plots and specific statistical tests. The Egger test was used to directly assess funnel plot asymmetry.³⁷ A significant regression slope suggests potential asymmetry in the funnel plot, indicating publication bias.³⁷

To evaluate the effect of microgravity exposure in space on the lumbar spine, we analyzed the observed changes in variables before and after spaceflight. The meta-analysis was conducted using the standardized mean difference (SMD). SMDs of 0.2, 0.5, and 0.8 are considered small, medium, and large, respectively.³⁸ A random-effects model was fitted to the data, and the amount of heterogeneity.^30,31 There is not a minimum number of articles required to perform a meta-analysis; therefore, we included at least two articles to examine associations.^28,29 Tau-squared was estimated using the restricted maximum-likelihood method.³⁹ In addition, Cochran’s Q test for heterogeneity and the I² statistic were reported.^33,34 If any heterogeneity was detected, a confidence interval for the true outcomes was also provided. Studentized residuals and Cook’s distances were used to examine whether any studies were outliers or influential within the model’s context.³⁰ Studies with studentized residuals larger than the 97.5th percentile of a standard normal distribution, adjusted for Bonferroni correction, were considered potential outliers.³⁰ Studies with Cook’s distances larger than the median plus six times the interquartile range of Cook’s distances were considered influential.⁴⁰ Rank correlation tests and regression tests, using the standard error of the observed outcomes as a predictor, were employed to check for funnel plot asymmetry.³⁷

Results

Results of the Search

Two researchers independently searched the databases and identified 115 records after removing duplicates (Figure 1). After analyzing the articles by “Title” and “Abstract”, 20 records were selected. After applying the inclusion and exclusion criteria, in the “Full text” analysis, finally, 11 articles^{1,13,14,41–48} were included in this review. Interrater reliability for screening the titles and the abstracts retrieved was substantial (Kappa = 0.85). Interrater reliability for evaluating the eligibility of the 20 randomly selected full-text articles was appropriate (Kappa = 0.70).

Figure 1 PRISMA Flow Diagram.

Characteristics of the Articles Included

Of the 11 studies included, 6 (54%)^{1,13,14,41–43} were prospective observational cohort studies and 4^45–48 also had an intervention (post-flight rehabilitation) and one⁴⁴ include an ultrasound protocol. The studies were published between 2014 and 2023. They were predominantly conducted in the United States (64% n= 7 studies),^{1,13,41–44,48} two in Australia,^45,46 and two in Germany^14,43 (Table 1).

Table 1 Characteristics of Studies and Participants Included

Characteristics of the Participants

Of the 11 studies included in the review, 10 analyzed human samples (n=93)^{1,13,14,41,43–48} and one study analyzed mouse samples (n=24).⁴² The human samples^{1,13,14,41,43–48} had a simple sizes ranging from 6 to 20 participants with a mean age ranging from 38 to 55 years. Two studies analyze same samples.^1,43 The animal study⁴² included a 24 mice divides into two groups, spaceflight and control with the same environmental characteristics except for the exposure to microgravity in the spaceflight group (Table 1).

Characteristics of Spaceflights

All studies included (n=11)^{1,13,14,41–48} assessed participants before and after the spaceflight, while four studies^13,14,44,46 also evaluated participants during the flight.

The human spaceflights lasted between 14 days and 6 months. The post-spaceflight assessments varied significantly among the human studies. Three studies^1,43,44 conducted only one post-flight assessment. These single evaluations also differed, being conducted immediately after the flight⁴⁴ or within the first three months,¹ or at six months.⁴³ Five studies^{13,14,41,45,46} conducted multiple post-flight assessments, with only one study including a long-term follow-up at 12 months.⁴¹ Four studies additionally performed rehabilitation interventions after spaceflight exposure (n=4 studies),^45–48 with only one study⁴⁸ including a long-term follow-up at 1, 2, and 4 years after the flight (Tables 1 and 2).

Table 2 Objectives by Studies and Spaceflight Assessment

The animal spaceflights study lasted 15 days,⁴² with post-spaceflight assessments conducted 48 hours after landing. In this study, sixteen C57BL/C mice (space flight group, n=8; ground-based control group, n=8) were sacrificed immediately after the spaceflight. The assessments focused on the biomechanical properties of the lumbar and caudal discs, specifically measuring physiological disc height and conducting compressive creep tests to evaluate parameters such as endplate permeability, nuclear swelling pressure strain dependence, and annular viscoelasticity.

Physiological Spine Changes in Low Back After Space Flights

The physiological impact of spaceflight on the human body leads to significant changes in spinal health. Astronauts experience notable alterations in spinal structures after spaceflight, affecting both muscle characteristics and lumbar mobility. The studies included in our analysis highlight physiological changes across four domains: 1) spinal pathologies, 2) disc dimensions and lumbar lordosis, 3) muscle atrophy, and 4) range of motion (ROM) (Table 3).

Table 3 Spine Physiological Changes in Low Back Before and After Space Flights

Spinal pathologies were evaluated in three studies.^41,43,44 Specifically, eight spinal pathologies were assessed: lumbar disc herniation, disc desiccation, disc degeneration, osteophytes, intervertebral disc bulge, lumbar endplate irregularities, lumbar facet arthropathy, and adjacent high-intensity zones. Spinal structures were examined before and after the flight using ultrasound⁴⁴ and Magnetic Resonance Imaging (MRI).^41,43 One study⁴⁴ found one lumbar hernia, three new osteophytes, two new intervertebral disc bulges, and nine new cases of disc desiccation post-flight.

The disc size was evaluated in two studies (one in humans and one in mice)^1,42, lumbar lordosis in one study,⁴³ and water content in two studies.^41,43 Significant changes in caudal intervertebral disc size before and after the flight were found in mice, but not in the lumbar region.⁴² In humans, a decrease in the intervertebral disc size was observed in the L1-L2, L3-L4, L4-L5, and L5-S1 segments.¹ All studies reported changes^41,43 in the water content in the intervertebral disc, but none were statistically significant. Specifically, a decrease in water content was found in the L1-L2, L2-L3, L3-L4, and L1-S1 segments, while an increase was observed in the L4-L5 and L5-S1 segments after spaceflight.

We carried out a meta-analysis to explore the differences in water content of intervertebral discs before and after spaceflights. A total of k=10 samples were included in the analysis. The estimated SMD based on the random-effects model was −0.052 (95% CI: −0.347 to 0.242) with the majority of estimates showing an decrease in water content after spaceflight (60%). Therefore, the average outcome did not differ significantly from zero (z = −0.350, p = 0.725) (Figure 2). These results suggest that exposure to microgravity during spaceflight does not lead to significant changes in the water content of intervertebral discs. There was no significant heterogeneity in the samples (Q p=0.739; Tau=0.0; I²=0%). An examination of the studentized residuals revealed that none of the studies had a value larger than ±2.8070, hence there was no indication of outliers in the context of this model. According to the Cook’s distances, none of the studies could be considered to be overly influential. Neither the rank correlation nor the regression test indicated any funnel plot asymmetry (p = 0.600 and p = 0.842, respectively) (Figure 3).

Figure 2 Forest Plot of Standardized Mean Differences in Intervertebral Disc Water Content Before and After Spaceflight.

Figure 3 Funnel Plot Assessing Publication Bias in Studies of Intervertebral Disc Water Content Before and After Spaceflight.

Muscle atrophy was the most studied outcome, with six studies^{1,41,43,45,46,48} investigating this aspect. The muscles examined included the multifidus, erector spinae, transversus abdominis, internal oblique, external oblique, psoas, quadratus lumborum, and lumbar paraspinals. Both the cross-sectional area (CSA) and the functional cross-sectional area (FCSA) were calculated. Findings of muscle atrophy were observed in all muscles both before and after the flight.

We carried out a meta-analysis to explore the differences in the CSA of the lumbar multifidus before and after spaceflights. A total of k=8 samples were included in the analysis. The estimated average SMD based on the random-effects model was 0.743 (95% CI: 0.239 to 1.248; p = 0.003) indicating a moderate to large effect size³⁸ (Figure 4). The majority of the estimates were positive (88%), suggesting a consistent trend of increased CSA in the lumbar multifidus post-spaceflight. These findings imply that exposure to microgravity during spaceflights leads to significant hypertrophy of the lumbar multifidus muscle. The Q-test for heterogeneity was not significant, but some heterogeneity may still be present in the true outcomes (Q = 13.180, p = 0.067, tau² = 0.246, I² = 47.6%). A 95% confidence interval for the true outcomes is given by −0.351 to 1.839. Hence, although the average outcome is estimated to be positive, in some studies the true outcome may in fact be negative. An examination of the studentized residuals revealed that none of the studies had a value larger than ± 2.734 and hence there was no indication of outliers in the context of this model. According to the Cook’s distances, none of the studies could be considered to be overly influential. Neither the rank correlation nor the regression test indicated any funnel plot asymmetry (p = 0.719 and p = 0.453, respectively) (Figure 5).

Figure 4 Forest Plot of Standardized Mean Differences in Multifidus Muscle Size Before and After Spaceflight.

Figure 5 Funnel Plot Assessing Publication Bias in Studies of Multifidus Muscle Size Before and After Spaceflight.

Additionally, ROM in the lumbar spine was evaluated in two studies.^41,43 Flexion-extension and lateral movements were assessed actively and passively by vertebral segments. In active flexion-extension, reductions in ROM were found at the L2-L3, L3-L4, L4-L5, and L5-S1 levels in both studies.^41,43 One study⁴¹ found reductions at L1-L2, while another⁴³ found an increase. In passive flexion-extension, the L1-L2 and L5-S1 segments showed reduced ROM, while the rest showed increases, though none were statistically significant.⁴³ Lastly, active lateral ROM was evaluated in only one study,⁴¹ which found reductions in ROM across all segments after the flight.

Additionally, we carried out a meta-analysis to explore the differences in ROM before and after spaceflights. A total of k=10 samples were included in the analysis. The estimated average SMD based on the random-effects model was 0.490 (95% CI: 0.069 to 0.910, p = 0.022), indicating a moderate effect size³⁸ (Figure 6). The majority of the estimates were positive (70%), suggesting a consistent trend of increased ROM post-spaceflight. These findings imply that exposure to microgravity during spaceflights leads to a significant improvement in the ROM.The Q-test for heterogeneity was not significant, but some heterogeneity may still be present in the true outcomes (Q = 16.502, p = 0.05, tau² = 0.20, I² = 46.20%). A 95% confidence interval for the true outcomes is given by −0.498 to 1.478. Hence, although the average outcome is estimated to be positive, in some studies the true outcome may in fact be negative. An examination of the studentized residuals revealed that none of the studies had a value larger than ± 2.807 and hence there was no indication of outliers in the context of this model. According to the Cook’s distances, none of the studies could be considered to be overly influential. Neither the rank correlation nor the regression test indicated any funnel plot asymmetry (p = 0.380 and p = 0.731, respectively) (Figure 7).

Figure 6 Forest Plot of Standardized Mean Differences in Lumbar Range of Motion Before and After Spaceflight.

Figure 7 Funnel Plot Assessing Publication Bias in Studies on Lumbar Range of Motion Before and After Spaceflight.

Pain During and After Space Flight

Four studies assessed pain,^13,14,43,44 three during the flight,^13,14,44 three upon landing,^13,14,44 and one also evaluated pain at 12 months post-flight.⁴³

During the flight, a high percentage of astronauts developed LBP (70%-85%).^14,44 Additionally, in the study by Pool-Goudzwaard et al,¹⁴ astronauts reported a mean pain intensity of 5 out of 10 points. None of the astronauts who were pain-free during the flight had a history of LBP on Earth.¹⁴ Out of the 12 astronauts without a history of LBP before the flight, 4 experienced it during the flight.¹⁴ There was a significant difference between the proportion of astronauts with and without previous back pain, and in the duration of LBP episodes (P < 0.01).¹⁴ The most commonly reported regions of pain included the iliac crest at the posterior iliac spines on both sides, a broad central lower lumbar region, a small area at the height of the iliac crest, and at L5.¹⁴ The main activities that triggered LBP were unknown, with 45% reporting pain after sleeping¹⁴ (Table 4).

Table 4 Low Back Pain Incidence During and After Space Flights

To assess the incidence of pain during spaceflight, a random-effects model with a total sample size of k = 3 was used. The estimated effect of pain during spaceflight was 0.768 (SE = 0.075, Z = 10.1, p < 0.001, 95% CI = 0.620–0.917), indicating that 77% of astronauts experience pain during spaceflight (Figure 8). There was no significant heterogeneity observed among the included studies (Q value = 0.987, p-value of 0.611; tau = 0.000, tau² = 0, SE = 0.0199, I² = 0%, H² = 1.00).^33–36 Furthermore, the Egger test found that the regression slope was not significant (Z = 0.651, p = 0.515), suggesting no publication bias in the analyzed studies³⁷ (Figure 9).

Figure 8 Forest Plot of the Incidence of Low Back Pain During Spaceflights.

Figure 9 Funnel Plot Assessing Publication Bias in Studies on the Incidence of Low Back Pain During Spaceflights.

After the flight, astronauts also experienced pain ranging from 10%¹⁴ to 100%,¹³ and at 12 months, 33% still had pain.⁴³ One study¹³ assessed the pain of two astronauts during and after a 17-day spaceflight. Both astronauts reported musculoskeletal pain, managed with anti-inflammatories and stretching techniques during the flight.¹³ Pain levels returned to baseline three months after landing.¹³ Pain questionnaires revealed intense pain experiences during and immediately after the flight.¹³

To assess the incidence of acute pain following spaceflight, a random-effects model was employed with a total sample size of k = 3. The estimated effect of pain during spaceflight was 0.47 (SE = 0.242, Z = 1.95, p < 0.052, 95% CI = −0.003–0.943), indicating that 47% of astronauts experience pain during spaceflight (Figure 10). Significant high heterogeneity was observed among the included studies (Q = 14.814, p-value < 0.001, τ = 0.385; τ² = 0.1483 SE = 0.1832; I² = 86.5%; H² = 7.407).^33–36 Furthermore, the Egger test found a significant regression slope (Z = 3.819, p < 0.001), suggesting publication bias in the analyzed studies³⁷ (Figure 11).

Figure 10 Forest Plot of the Incidence of Acute Low Back Pain After Spaceflights.

Figure 11 Funnel Plot Assessing Publication Bias in Studies on the Incidence of Acute Low Back Pain After Spaceflights.

Qualitative interviews allowed the astronauts to describe their pain experiences during the flight.¹³ When exposed to microgravity, Astronaut 1 described experiencing lower back pain and headaches. Although the lower back pain decreased after two to three days on the International Space Station (ISS), they continued to experience “a higher number of headaches than usual”. They also mentioned feelings of “nausea, disorientation, and general discomfort”, which gradually improved in two to three days. Notably, they expressed relief at the absence of shoulder pain during the seventeen days in space, stating: “I didn’t notice any shoulder pain at all during the seventeen days I was in space. That was great!”. However, upon returning to Earth, they reported that the shoulder pain had returned “to where it was before”. Additionally, they mentioned experiencing muscle pain and stiffness, especially in their calves, immediately after return, likening it to having had intense calf training. They also described lower back pain, characterized as “spasms”, although seven days after their return to Earth, they reported that muscle pain and lower back pain had mostly decreased, commenting: “my muscles are getting used to carrying my body in 1G”.

Astronaut 2 described previous episodes of common pain, usually related to injuries such as a tibia fracture four years prior.¹³ During space training and aboard the ISS, they experienced predictable discomfort in their tibia, exacerbated by exercise and prolonged standing. In microgravity, they reported significant lower back pain from the outset and also mentioned pain in their left iliotibial band. Upon returning to Earth, they continued to feel pain in their distal tibia, especially when initiating movement after prolonged periods of rest.

Finally, sensory changes in both astronauts included increased thresholds for mechanical touch detection, temporal summation of pain, heat pain thresholds, and differences in conditioned pain modulation after the flight.¹³ Therefore, this study suggests that spaceflight can affect various aspects of sensory perception and regulation in astronauts.

Risk of Bias in Studies Included

The risk of bias was analyzed with specific scales that were used for studies in humans and animals with an adequate level of agreement among examiners (Kappa index = 0.77). In the studies involving humans,^{1,13,14,41,43–48} we found that all the studies indicated a low risk of bias in the “Prognostic Factors Measurement” and “Outcome Measurement” domains. The majority of issues were found in “Study Attrition”, “Study Confounding”, and “Statistical Analysis” where the risk of bias was moderate or high. In the article involving animals,⁴² evaluated by SYRCLE,²⁰ the authors did not randomize the sample and did not blind the evaluator of the variables (Table 5).

Table 5 Risk of Bias of Studies Included

Quality of Studies Included

The quality of the studies was evaluated with an inter-evaluator agreement of a Kappa index of 0.75. All the studies analyzed outcomes before the flight and used a valid and reliable scale for measuring these outcomes. None of the studies reported sample size calculations, all assessed the exposure only once over time, and none analyzed potential confounding factors such as sex or age in relation to pain (Table 6).

Table 6 Quality of Studies Included

Quality of Evidence

The GRADE-based evaluations^25,26 were previously pilot tested with 2 reviewers for 30% of outcomes, achieving a substantial level of agreement (Kappa = 0.80). Study limitations were finally assessed by 2 independent reviewers, who had lower interrater reliability than in the pilot test, but still acceptable (Kappa = 0.71). The GRADE Assessment reveals low-quality evidence in “Trunk muscle atrophy”, and moderate-quality in “Spinal pathologies”, “Disc size”, “Paraspinal muscle atrophy”, “Range of motion”. (Table 7).

Table 7 Quality of Evidence of Changes on Spinal Pathologies in Low Back After Space Flights Assessed by GRADE System

Discussion

In this study we summarize the physiological changes in low back after spaceflights, and we describe the incidence of inflight and chronic LBP of astronauts. The results of 11 studies show several changes in the spine after short space flights and acute and chronic pain in both humans and mice.^{1,13,14,41,43–48} Those studies included 93 astronauts that represent the 20% of the astronauts population in the history of spaceflights (500 people).⁴⁹

Spinal Pathologies and Disc Dimensions

On Earth, intervertebral discs maintain their health by bearing loads and retaining water, thanks to proteoglycans, essential components that help absorb impacts.^50–55 During a prolonged stay in space, the intervertebral discs of astronauts undergo significant changes due to the lack of gravity.^{1,13,14,41–48}

Space flights are associated with several changes in spine structure, particularly in the intervertebral discs. The absence of compressive loads in space, causes a decrease in the proteoglycan content of the discs.^50,52–55 Discs are continuously remodeled according to daily mechanical loads,⁵⁶ with less load (or total absence in space), the numbers of proteoglycans are reduced, and therefore the discs retain less water, affecting their ability to absorb impacts and making them more prone to herniation and pain.^50,52–55

When astronauts return to Earth and their discs start bearing weight again, proteoglycan levels can recover since the intervertebral disc’s extracellular matrices are continuously remodeled.⁵⁶ Studies have observed that discs recover their proteoglycan content after fourteen days of normal physiological loading, which could explain the adaptation of intervertebral discs to the microgravity environment of space and their subsequent adaptation to the terrestrial environment after landing.⁵² However, we identified a significant gap in the literature regarding mid-term evaluations post-landing (eg, 30 days), which could help better understand these findings.

Muscle Atrophy

Muscle atrophy associated with space flights represents a significant challenge for the health and performance of astronauts. This phenomenon not only affects load distribution and spinal stability upon returning to Earth’s gravity, but also has prolonged implications for recovery and muscle function.^47,48,57,58 It is worth noting that muscle atrophy has been the most studied factor in the studies included in this review, demonstrating significant concern. However, its effects on space flights are also beginning to be understood.^{1,41,43,45,46,48}

Microgravity results in mechanical unloading of the muscles which may produce muscle atrophy during space flights.⁵⁷ On Earth, gravity provides a constant load that muscles must resist to maintain posture and perform movements. In space, the absence of this constant load leads to a decrease in muscle activity and consequently, a reduction in muscle mass and strength.^{1,41,43,45,46,48} This atrophy is exacerbated by the duration of the flight, reduced physical activity, and changes in nutrition and metabolism.^57,58

The muscles of the lumbar region, including the spinal erectors, multifidus, psoas, quadratus lumborum, transversus abdominis, and internal oblique, are crucial for lumbar spine stability.^59,60 Multifidus atrophy, particularly pronounced at levels L3, L4, and L5 after spaceflight,^41,45,46 is of particular concern due to its central role in lumbar stabilization^61,62. The atrophy of lumbar region muscles during and after spaceflight may compromise the spine’s ability to maintain necessary rigidity, increasing the risk of injuries and lower back pain.^57,61–63

Among patients with chronic lower back pain, multifidus atrophy is particularly notable, suggesting a relationship between muscle loss and pain perception.^57,61–63 This finding is consistent with pain localized in the lumbar region during and after spaceflight, indicating that muscular atrophy may affects the physical function of astronauts.^13,58

Muscle attenuation refers to a reduction in muscle quality or density, which can make muscles less efficient in their functions.⁶³ The muscle function is affected by a decrease in attenuation in the psoas, erector spinae, multifidus and quadratus lumborum muscles.^{1,41,43,45,46,48} This attenuation, occurring independently of atrophy, suggests changes in muscle composition, possibly related to loss of muscle density or alterations in contractile properties.^45,46,48,57 The persistence of this attenuation, even after rehabilitation, underscores the potential need for the development of effective recovery postflight programs.

During spaceflights, the muscle atrophy and reduction of muscle strength, associated with the lack of gravity leads to a significant decrease in the ability of these muscles to generate force.⁶³ This loss of strength is further compounded by the infiltration of fat into the muscles, a process that further reduces their functional capacity and affects the muscle’s efficiency in supporting the spine and protecting it from mechanical stress.^57,61–63 This reduction in the muscle’s ability to generate force not only compromises general physical function during and after the flight but also makes it more difficult to recover spinal stability, prolonging the rehabilitation process in the medium and long term.^57,58 In rehabilitation, it is crucial to design specific programs that focus on restoring muscle strength to regain the ability to bear loads and perform functional movements. Without appropriate intervention, the loss of strength can perpetuate muscle dysfunction and extend the time needed for full recovery, affecting astronauts’ effective reintegration into their daily and professional activities.

Range of Motion and Lumbar Lordosis

The absence of gravitational load on the spine alters the normal patterns of compression and tension experienced by the muscles and structures of the lumbar spine.^4,57 This can lead to deconditioning of the paravertebral and abdominal muscles, manifested as atrophy and reduced muscle attenuation.^{1,41,43,45,46,48,57} The highest levels of muscle atrophy in the multifidus muscle occurred at the L4-L5 and L5-S1 levels,^41,46 coinciding with the greatest changes in ROM in the lumbar region.^41,43 Therefore, it appears that atrophy of the lumbar muscles, especially the lumbar multifidus, will result in decreased mobility in that region. This is because the muscles will have reduced contractile capacity and mobility, thus reducing the ROM in the affected vertebral segments.^{41,45,46,48,61,62}

ROM assesses the functional capacity of the spine to move without restrictions, serving as a key measure for identifying limitations caused by muscle atrophy following exposure to microgravity.^{41,45,46,48,61,62} These limitations in ROM may contribute to increased LBP, as reduced mobility impairs the proper distribution of loads in the spine, exacerbating the risk of injury.^{1,41,43,45,46,48,57} In rehabilitation, improving ROM is essential not only for reducing pain but also for restoring functional movement patterns. Addressing ROM limitations early in the recovery process can enhance the effectiveness of strength training and reduce the overall time needed for rehabilitation.

Weightlessness also has a significant impact on the sensory perception and proprioception of astronauts.^64,65 On Earth, gravity provides constant sensory feedback through receptors in the joints, muscles, and skin, which are essential for precise control of movements and posture.^{9,10,41–43,57} The lack of gravity reduces or eliminates the gravitational forces acting on the body, particularly on the spine.^{6,43,52,57,58} This can lead to a decrease in the sensory stimulation that proprioceptive receptors normally receive, affecting the brain’s ability to process and adjust the position and movement of spinal joints.^64,65 As a result, astronauts may experience a reduction in the accuracy and coordination of lumbar spine movements, thereby reducing the ROM in the lumbar spine.^41,43

Pain During and After Space Flight

The onset of in-flight LBP often occurs within the first twenty-four hours and may persist throughout a mission.^14,44 In-flight surveys conducted over fifteen days found that pain incidence and intensity were highest in the first two days, after which there was a steady decrease in both incidence and intensity and no pain was reported after the ninth day.¹⁴ The astronauts differentiated between types of pain, with the majority experiencing continuous pain (as opposed to intermittent pain) on the first day.¹⁴ The incidence of post-flight LBP was significantly lower after a 15-day flight compared to that of long duration flight (10% vs 40–50%).^6,14 These results corroborate other reports of in-flight LBP primarily resolving after five days and rarely persisting beyond twelve days.⁹

Therefore, there appear to be two classes of LBP in space. On one hand, acute changes occurs within the first 24–48 hours and are responsible for in-flight LBP, coined “space adaptation pain”, within the first 9–15 days.^13,14,44,46 Due to their minimal impact on post-flight LBP and disc herniation, it is unlikely that they lead to lasting decreases in load-bearing ability after reintroduction to terrestrial gravity. On the other hand, prolonged changes occur anytime after 12–15 days and appear to be unrelated to the occurrence of in-flight LBP.^{1,13,14,41–48} These changes will likely impair spinal loading ability and appear mainly responsible for post-flight symptoms and injury.^{1,13,14,41–48}

Microgravity-induced physiological changes have been demonstrated to align with some correlates of LBP on Earth.^{1,13,14,41–48} The pathophysiology behind the in-flight LBP, post-flight disc herniation, and post-flight LBP in astronauts requires further study.

Limitations and Future Research

Despite the valuable insights provided by this study, there are several limitations that should be considered. While the number of astronauts included represents approximately 20% of all astronauts historically,⁴⁹ the small sample sizes in the studies do not allow for robust causal analysis.^66–68 Future research could focus on increasing sample sizes to enhance statistical power analysis. Additionally, moderate to high risks of selection bias and methodological limitations, particularly in follow-up and statistical analysis, may affect the robustness of conclusions drawn.⁶⁹ Addressing these concerns could involve implementing stricter protocols for participant follow-up and employing advanced statistical methods to mitigate bias. On the other hand, the variability in assessment methods across studies, including analyses of repeated measures within the same subjects but at different studies, introduces potential inconsistencies in results and complicates direct comparisons.²⁶ Future studies should aim for standardized assessment protocols to improve data comparability and reliability. While the role of the multifidus muscle in low back pain has been extensively studied, recent research highlights the critical role of the erector spinae.^70,71 Future studies on the effects of spaceflight on spinal musculature should incorporate a more comprehensive evaluation of both muscle groups in humans and animals. This would provide a deeper understanding of how different back muscles respond to microgravity and contribute to low back pain and post-flight recovery. Lastly, the limited number of studies investigating pain in spaceflight underscores the need for comprehensive research in this area. Further investigations could explore pain experiences across different mission durations and conditions, potentially informing targeted interventions to mitigate lumbar pain in astronauts. These identified limitations highlight avenues for future research aimed at strengthening the evidence base and enhancing understanding of the complex interactions between physiological changes, pain, and the spaceflight environment.

Conclusions

Astronauts experience muscle atrophy in the lumbar multifidus with a moderate to large effect, especially in the L4-L5 and L5-S1 segments, after space flights. Additionally, there is a reduction in the ROM with a moderate effect, along with disc herniations and disc dehydration. Seven out of ten astronauts develop pain during the spaceflight, four out of ten develop acute pain after spaceflight, and three out of ten develop chronic pain. Furthermore, the quality of this evidence ranges from moderate to low, and moderate to high risks of bias were identified in the studies, particularly in areas such as follow-up loss and statistical analysis, underscoring the need to enhance methodological quality in future research.