The ecacy of NSAID in performance improving and pain management in military physical aptitude test. An observational study in the military medical personnel

The Chinese military is deepening the strenthening reform and enhancing physical training standards. The sudden increasing in training requirements and outline has increased the pressure of the logistics units, such as medical personnel. Using over-the-counter (OTC) analgesics, such as nonsteroidal anti-inammatory drugs (NSAIDs) in the military physical aptitude test (MPAT), has been described as helpful for reducing of post-exercise myalgia (PEM) and improving performance. To verify this hypothesis, we designed and carried out this study. The objective was to explore the effect of NSAID in the performance improvement and relieving of PEM in MPAT.


Introduction
According to the military training mobilization requirements issued by the China Central Military Commission, PLA is continuing to deepen the level and intensity of military physical training [1]. The ensuing problems are the increasing military training injuries and other issues surrounding MPAT [2]. The military medical personnel, which was required to reach a lower test standard than the eld forces.
However, in order to meet the needs of combat-speci c tasks, they still need to achieve stated standards, which varies according to age and gender as well as to pace and distance to be achieved [3]. The MPAT for logistic personnel assesses including a series of items, such as sit-ups, push/pull-ups, long distance and shuttle runs. Scores ranges from insu cient to excellent. Like athletes, such training assessment items can cause muscular pain and even training injuries. Especially for military medical personnel whose training intensity is lower than that of eld soldiers.
Analgesics, such as NSAID and paracetamol, are widely consumed by athletes worldwide [4]. Although these drugs are used to reduce short-term pain and in ammation, they have also been shown to modulate muscle protein turnover. Emerging evidence con rmed that NSAID might acutely improve important endurance parameters, possibly through increased pain tolerance [5]. Etoricoxib have been demonstrated to inhibit cyclooxygenase-2 (COX-2) activity, which might explain the reduced anabolic response to acute exercise bouts [6]. In addition to being used to treat arthritis, it is also widely used treated for minor injuries such as blisters, sprains, tendonitis and contusions. Though greater awareness and risk-bene t analysis were advocating among persons on the potential adverse effects of these drugs.
Nevertheless, The use of etoricoxib in MPAT is still described widespread and therefore worthy of note.
In all classes of athletes, NSAID are one of the most commonly used medications for the treatment of musculoskeletal pain and in ammation associated with training, competition or soft tissue injuries, or to gain a competitive advantage [7]. In addition to injury treatment, NSAID usage is high as a prophylactic treatment for anticipated pain, as well as to enhance the recovery of injuries sustained during an athletic event [8] [9]. Research of this phenomenon in the military environment are still limited because knowledge is needed for the military training, and the mechanisms of injury or simulations of the different activities. This research project aimed therefore to, rst, determine the NSAID's effect on relieving PEM and, second, to determine whether NSAID is a factor for the performance improvement in MPAT.

Participants' characteristics
This study was approved by the ethical research board of Air Force Medical University, participants themselves decided whether to take medicine based on past habits. An initial questionnaire was administered to collect necessary information about the subjects. The content of the questionnaire mainly includes general information such as gender, age, height and weight, training time and intensity before the test, test score (3000m runing and sit-ups), and PEM evaluation (VAS score of LEs, ABS). Inclusion criteria include: 1. Voluntary participation in the test and complete the form; 2. Age ranging from 25 to 35 years (The assessment criteria for this age range are similarly); 3. Completion of all MPAT items; 4. No serious underlying diseases that interfere with the evaluation results. Exclusion criteria were as follows: 1. Refuse to participate in the survey, or the contents of the form are incomplete; 2. BMI meets the obesity standard (> 25); 3. No test score due to fouls; 4. History of systemic chronic disease, such as heart disease, diabetes, neuro-musculo-skeletal system diseases; 5. History of allergy to non-steroidal anti-in ammatory drugs. Finally, 97 data were included in the study, demographic variables and paticipants' clinical characteristics are summarized in Table 1.

Observation indicators
The MPAT program includes 3000m running, shuttle run, sit/pull-ups. Among them, 3000m running and sit-ups were seemingly more affected by drugs. The muscle endurance and explosive power were evaluate by these two exercises respectively. Two different muscle groups of the body were mobilized.
Therefore, these two groups of muscles have been regarded as the main observation items due to more likely to induce pain. Another interfering factor is the training situation of the subjects. Exercise habits such as running and sit-ups were potential factor other than analgesics could have been responsible for the improvement scores and possibility of pain relieving. We recorded adherence to the exercise habit as "yes" or "no". Running performance is recorded in 'mins', while sit-ups are recorded in 'pcs'. The VAS score includes Lower Extremities (LEs) and abdominals (ABs).

Statistical analysis
The data are expressed as means and standard derivations and were analyzed using SPSS20.0 software.
The Wilcoxon rank-sum test and the Mann-Whitney U test were used to compare for the data inconsistent with normal distribution test, independent sample t test was used for comparison between groups, and paired t test was used for comparison within groups. A statistically signi cant difference was assumed at a probability of less than 0.05.

Results
Comparison of the overall situation between the two groups

Comparison of sub factors intra groups
For 3000m running, as a matter of fact, whether taking analgesic or not had no obvious effect on the result intra sub-groups (P > 0.05). It seems to support the factor which leads to a difference of performance in the running score mainly by exercise was insisted or not. This negation result denied, at least partially, the hypothesis that analgesic are effective in improving performance, especially in endurance events (Fig. 1). In terms of sit-ups scores, taking analgestic itself can improve test scores among people who did't exercise regularly. Simply keeping exercise can also lead to good effect, which were similar to those of taking analgestic. Therefore, this may support the view that taking medicine is as effective as exercise (Fig. 2). In VAS (LES), these two factors have seemingly equal effect and an interaction (Fig. 3). Analgesics are more effective in VAS (ABs) than exercising. This is just like the conclusion of our previous analysis: 3000m running is the evaluation of endurance, and sit-ups is the evaluation of explosive power. Analgesics seem to be more effective for muscle explosive tests and the pain after that (Fig. 4).

Discussion
This is known as the rst study on the effect of NSAID on the performance and analgestic in MPAT.
Etocoxib are some of the most commonly used drugs in the world, 12% of adults report taking NSAIDs regularly [10]. This ratio is as high as 75% among young athletes [11]. NSAID have been demonstrated to inhibit cyclooxygenase activity, which might explain the reduced anabolic response to acute exercise bouts. Consistent with this, NSAID has been reported to interfere with muscle hypertrophy and strength gains in response to chronic resistance training in young individuals. The use of NSAIDs in the military is also common, but less reported. In the US Army, more than 80% of soldiers lled at least one NSAID prescription annually [12]. Although the use of NSAID may bring a series of complications and other possible hidden risks, including cardiovascular disease, peptic ulcers, hyponatremia, and even stress fractures [13][14] [15]. However, the use of drugs is still widespread.
Anyway, our research con rms that etocoxib can indeed alleviat PEM after physical training. It has been proved that a COX-2 inhibitor has an analgesic effect by inhibiting the synthesis of prostaglandins [16].
This analgesic effect is obvious for musculoskeletal pain. People who adhere to exercise habits will produce fewer pain factors and lactic acid then gain the therapeutic effect on chronic pain [17]. Even so, NSAID still has an additional analgestic effects. This also proves that athletes have been training, but there are still people taking drugs. Explosive muscle tests were more likely to induce PEM, people are more inclined to take NSAID when participating in such projects [18].
Etocoxib was generally effective in improving MPAT results, at the same time, relieved PEM. The 3000m running performance was improved by nearly 1 minute, while in the sit-up event, the performance was improved by nearly 10pcs overall. Although some possible in uencing factors of the two groups of data, including gender, age, BMI and other baseline data, have been proved to be balanced and comparable.
However, considering the difference in daily training habits, a comparative analysis of two groups of two factors was carried out. Another promising founding was that etocoxib is not the decisive factor in the 3000m running performance. In contrast, daily endurance training was the decisive factor affecting performance. While in the sit-up test, for people who have not taken drugs, daily training can improve test scores. For people who have not, it can also have the same antalgic effect. This may indicate that NSAID was more effective for muscle power testing. This is in line with a recent Brazilian's study on military soldiers which demonstrated that training injuries of the LEs are the most common military training injuries [19]. Therefore, they came up with a series of recommendations for lower limb training. Our results are noteworthy that both systematic training and NSAID can signi cantly alleviate pain of the lower limbs. NSAID may not improve the evaluation results of endurance running events, but it can indeed reduce the PEM of the lower limbs after the evaluation. Taking analgesic is especially effective for PEM for muscle power test. The abdominal muscle PEM after sit-ups was signi cantly improved by NSAID.
In the 3000m running test, the overall performance improvement seemed more like the bene ts of continuous exercise than that of NSAID. Although the muscle pain was relieved during the test, it did not improve the cardiac and pneumonic functions of the participants. Therefore, we observed the above results in the detailed analysis. As the overall pain score after the assessment was mild to moderate, we did not advocate the use of drugs to relieve this pain. Studies have shown that this type of pain can be completely relieved after 48 hours of rest. The sit-up test showed a completely different conclusion. We speculate from this that NSAID may also signi cantly improve the performance of the 100-meter run and relieve muscle pain, although assessment items do not include such items as "sprint running". But in real combat feild, short bursts of explosive running may be common [20].
There are a series of known and unknown risks associated with the use of NSAID, including hypernatremia, stress fractures, and muscle dissolution [21]. The usage of NSAID among the general public and athletes has always been questioned. Topical medication seems to achieve the same effect while reducing the side effects and risks of systemic medication. Given that systemic medication has many clear hazards, it is more concerned to nd better ways to improve performance and relieve pain [22]. Additionally, applying of formulation of topical dosage forms locally in proximity to the affected area can provide effective concentrations at the local target tissues to limit systemic exposure as well as adverse effects [23]. Therefore, if NSAID are worthy of promotion, is it possible to consider topical preparations instead of systemic medication.
An obvious shortcoming of this study was investigation with broader cohort coverage was unable to conduct. Military medical personnel was a special group whose professional characteristics are more inclined to work in the o ce and therefore relativly lack of daily training, and therefore possible to lead to a overall ghting capacity decreased. This feature makes us select this population as the research object.
Such research can better distinguish the actual effects of intervention factors and also has important value.
The sample size of our research is also insu cient, which limits the persuasiveness of the research results. It is a valuable practice to conduct a larger sample size survey among more military-related personnel groups, especially for prospective group-controlled trials.
To sum up, as far as we know, this is the rst study on the use of NSAID during MPAT. Although there are still limitations, however, the research results have certain reference signi cance. We prefer not to recommend the use of NSAID in MPAT, because the effect has not been truly re ected. In addition, the cost-bene t ratio of this behavior is not clear, although the use of over-the-counter drugs is voluntary. The prospects in this regard need to be further deepened by colleagues.
Additionally, applying of formulation of topical dosage forms locally in proximity to the affected area can provide effective concentrations at the local target tissues to limit systemic exposure as well as adverse effects. Therefore, if NSAID are worthy of promotion, is it possible to consider topical preparations instead of systemic medication.

Conclusions
The results of this study support the NSAID's effectiveness in relieving muscle pain during the physical tness test process and improving the assessment results, especially in the muscle power test items.
However, continuous and regular physical training is equally important, which can also achieve the effect of reducing pain. And in the endurance test project, its role is more obvious. The risks and harms of shortterm use of NSAID are not yet clear. Therefore, the military medical personnel should carefully choose to use analgesics during physical tness assessments.

Declarations
Availability of data and materials The datasets used during the current study are available from the corresponding author upon reasonable request.

Figure 1
Comparison of 3000m test scores. Figure 1 is histogram which shows the test results of the subgroups in 3000 meter run, there was no signi cant difference between A1 and B1; A2 and B2, actually. On the contrary, "continuous excersice" has a signi cant impact on the results in this project (*: P 0.05).

Figure 2
Comparison of sit-ups test scores. Figure 2 is histogram of sit-ups score. The results showed that NSAID can improve the test results in the group without "continuous exercise" (△ P < 0.05), but in the people with "persistent exercise", whether taking drugs or not has no obvious effect. Meanwhile, in those who did not take NSAID that "keep exercising" had a signi cant effect on improving performance (*: P < 0.05).

Figure 3
Comparison of VAS of lower extremities. Figure 3 is a histogram of pain's visual analogue score for lower extremities. It can be seen that the in uencing factors, whether taking NSAID or persisting in exercise, have independent in uence on the results respectively (*, △: P 0.05). There may be a superposition effect between the two in uencing factors on this observation index.