Influence of physical exercise in pain threshold in human: A systematic review

Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of that injury. Aerobic exercise has been widely studied in painful conditions subjects and is related for the improvement of the fragility syndrome, increasing the pain threshold/tolerance during and after its practice. For healthy subjects, aerobic exercise has already shown to prevent various diseases and strengthen the immune system, fighting infection diseases. The objective of this review was to report the modalities of aerobic exercises associated with the treatment of adjuvant pain reduction of experimental pain or tolerance) in the skeletal muscle system a systematic review of clinical studies. search the recommendation. were selected, reporting results related to pain modulation through aerobic exercise. A total of 20,790 studies from which we evaluated 110 records and, finally, we included 7 studies in the quantitative analysis, following the eligibility criteria. The results revealed that healthy men and women (about 97 patients) increased the pain threshold /tolerance through aerobic exercise. Protocols with different stimulations were evaluated. With low quality of evidence, it is indicated that aerobic exercise increases threshold / tolerance of peripheral pain in healthy people.


Introduction
Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential tissue injury or described in terms of this lesion [1]. It is fundamental to survival; acute pain demonstrates a harmful action given in a short period of time (by stimulation of delta nociceptive fibers in healthy people), but when the pain is chronic there is already an advanced inflammatory process and even a modulation of pain, given by time (by stimulation of the C fibers, when there is no central sensitization) [1][2][3][4][5][6].
In addition to the negative factors that pain promotes (as seen above), the high cost with health stands out. Pain has been highlighted as a "major socioeconomic problem" in various countries [7]. in the United States of America, at the beginning of 2012 an average of 116 million people were estimated to have a health problem (which brings discomfort and pain), with US $ 635 billion spent on treatments annually [7]. One of the ways to classify pain is through the pain threshold, which can be defined as the minimum stimulus needed to trigger pain in the individual. Pain is a phenomenon of subjective measurement, which is difficult to measure [8]. Some methods have been developed to measure pain thresholds in a systematic way, such as: pressure stimulus [9][10][11], measurement with thermal variance [12][13][14] and even use of electrical stimulation [15][16][17], making the more practical the understanding of pain in the various clinical pathologies and the severity of the diseases. These tools also allow for making experimental use of pain, in laboratories, for example.
Pain thresholds, in turn, are defined as minimum stimuli needed to induce or cause pain in the individual [18]. Studies involving both animals and humans have already demonstrated a possible association between chronic pain and reduction of pain thresholds [19,20]. Several factors determine these thresholds [21][22][23], one of the variables that has received great attention is physical exercise [24,25].
It is already understood that physical exercise promotes pain improvement and prevents /treats plenty of diseases, such as: cardiovascular diseases, cancer, arthrosis, type II diabetes, obesity, among others [26][27][28][29][30]. Studies involving large populations have shown that physically active individuals have a significant decrease in the risk of developing chronic pain [31,32].
The mechanisms involved in pain relief by exercise can be orchestrated by activation of endogenous opioids, such as beta endorphin, dynorphin and enkephalin, a factor observed in animals but still contradictory in humans, and activation of baroreceptors, which are cells that are located in the aortic arch and carotid artery and respond to the regulation of cardiovascular parameters (heart rate and blood pressure), modulating the pain threshold/tolerance [33,34]. Exercise in general, both aerobic and anaerobic, plays a fundamental role in analgesia, since it increases heart rate, activating the baroreceptor mechanisms and relating to the descending system of pain modulation, increasing the threshold [35,36].

Search strategy
A search was conducted using the following electronic databases via MEDLINE: PubMed; Web of Science; and Scopus. We searched for study records at the ClinicalTrials.gov, Current Controlled Trials and WHO-ICTRP (World Health Organization-International Clinical Trials Registry Platform), as well as abstracts published in congress proceedings through the Web of Science.
The following key words used were: (Chronic pain and Train) OR

Eligibility criteria
Studies evaluating aerobic exercise at any type were included in this review following the criteria: (1) healthy men and women at any Aerobic exercise is characterized as a method that varies energy consumption and respiratory exchange (O2 and CO2) with emphasis on the mobilization of fatty acids during its application, consuming more carbohydrate as the intensity of the training increases [37,38]. Aerobic exercise has been widely studied in subjects with painful conditions and is indicated for the improvement of the fragility syndrome by increasing the pain threshold during and after practice [2,4,36]. For healthy subjects aerobic exercise prevents various diseases and strengthens the immune system, becoming less exposed to contract an infection [5]. The objective of the present study is to identify, analyze and summarize existing evidence from randomized clinical trials investigating the effects of aerobic training on pain threshold and tolerance in healthy subjects.

Methods
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [39]. There is a 27item check list in PRISMA, that focus on ensuring a complete reporting of health care interventions. The inclusion criteria are exposed in figure 1.

Review process
The selection of studies was carried out by titles, abstracts and key words that were independently reviewed by two authors (PNOB and ZOAM) verifying duplications and using pre-established criteria for inclusion. After the basic screening the same authors selected the studies following the eligibility criteria above by full reading. Regarding the language, only studies written in English or Portuguese were included.

Data extraction
Articles were included from January 1980 until January 2019.
The characteristics of the studies extracted were authors, country, date, institution, conflict of interest, consent term, ethical approval, inclusion and exclusion criteria, number of women and men in the study, exercise modality, exercise period, physical exercise time performed in each session, weekly training, menstrual cycle and anatomical site of the measurement of the pain threshold/tolerance.
There was contact with the authors of the studies to obtain missing data. In cases of no response, we opted to exclude them in order to avoid any discrepancy in the comparison values.

Methodological quality and strength of evidence
We consider study limitations (bias risks), inconsistency, imprecision, indirect effect and publication bias (following PEDro scale). The quality of the evidence was checked as: High quality = it is very unlikely to change our confidence in estimating the effect with further research; Moderate quality = more searches are likely to have a significant impact on our confidence in the estimate of effect and may change the estimate; Low quality = more surveys are very likely to have a significant impact on our confidence in the estimate of effect and is likely to change the estimate; Very low quality = we are uncertain about the estimate.

Results
A classification of eligibility criteria of each study is included in table 1.
The methodological quality and strength of evidence of all studies are unanimous in the results, the pain threshold/tolerance was increased after aerobic exercise (ergometric bicycle or treadmill). The data is showed in table 2.
The characteristics containing the main information of each study are included in table 3.

Discussion
This systematic review exposes pain perception through pain threshold/tolerance in healthy subjects exposed to aerobic exercise. Seven studies were considered eligible, and based on the study classification, one study was classified as "moderate" in quality of evidence, three studies were classified as "low" in quality of evidences and three other studies were classified as "very low" in quality of evidences.
Aerobic exercise seems to modulate positively the pain threshold/ tolerance in healthy people during and shortly after its practice. In this sense, aerobic exercise, either performed in the form of walking or running on a specific ergometer (treadmill), or on a stationary bicycle show increasing the pain threshold/tolerance in healthy individuals. Possible explanations for this effect include increased heart rate analgesia, as there is evidence that there are common pathways between cardiovascular modulation and pain in the central nervous system [33,40].
One factor that modulate the pain threshold/tolerance in the studies was the exercise intensity. The studies provided the intensity of exercise, demonstrating improvement in pain threshold at 75% HR max, 75% VO 2 max and other kind of intensity measurements (watts, km/h and treadmill inclination), exposing that moderate/high intensity aerobic exercise improves pain threshold in healthy people.  Some studies demonstrate moderate and high intensity training to increase also, pain threshold/tolerance and pain perception [41][42][43].

Nº study Author/ year/ country Eligibility
With respect to frequency of training (volume), only one study did training more than one week (Jones, 2014), training 3 times a week for 6 weeks. The other studies did not specify the weeks. Hoffman, 2004 did 4 bouts of training but no specify the days and weeks. Meeus, 2010 did 2 bouts of specific aerobic exercise. Koltyn, 1996 and Lee, 2014 did not specify the bouts, supposing that this study was acute exercise effect. However, participants performing acute, two or three or bouts per week on nonconsecutive days, demonstrating statistically significant improvement in pain threshold, in isometric exercise (p<0.05), strength and coordination exercise (p<0.05), aerobic exercise (p<0.05) and resistance training (p<0.05) [40,[44][45][46].
Another spot in this study is that studies used only ergometric bicycle and treadmill exercises, not any other forms of aerobic exercise, such as swimming, rowing, skiing, etc. Swimming training demonstrated in the past to increases pain threshold in chronic pain subjects [47].
Advances have been made regarding the understanding of pain threshold/tolerance and exercise, there are several changes in pain threshold/tolerance between healthy subjects and pathologic. First, there is several differences between the pain modulatory through baroreceptor (pain modulation through cardiac impulse). Second, there is difference in the Central Pain Modulation (CPM) in the old days known as diffuse noxious inhibitory control (DNIC) in chronic condition. Finally, the nociceptive fibers regarding pain stimulus are different in healthy and pathological subjects. C fiber is attenuate in chronic conditions, intensifying the pain and elevating the stage to neuronal pain as well.
The present study demonstrated with low evidence quality that aerobic exercise increases pain threshold and tolerance in healthy subjects. Whetever, to understand how the pain threshold/tolerance can be effective in healthy subjects, studies must explain detailed method, such as, how many days of training per week, for how long, what intensity and the complementary information about the subjects.
The present review is not without limitations. First, the search was made only in English and Portuguese. Second, only one reviewer that performed the analysis of included studies, given higher risk of bias.
There is lack of information in the selected studies, it's became poor of information with respect of knowledge analysis. In the present study mostly of the found data are inconclusive. For this reason, caution must be used to interpreting the present results.

Practical applications
Analyzing the present review, some recommendations can be made regarding pain threshold in aerobic exercise in healthy human: i) Initiate aerobic exercise with a sport science professional; ii) Beginner should start the aerobic exercise in low intensity, increasing the volume through the weeks, and then the intensity; Zecchin-Oliveira AM (2020) Influence of physical exercise in pain threshold in human: A systematic review iii) One day a week of aerobic exercise is enough to elicit lower pain perception, but more days seems to better pain threshold. iv) Start aerobic activity in ergometric bicycle if you have any knee injury and strengthen the muscles including at least one strength training per week.
Researchers and practitioners must be aware that some of the recommendations above are still limited in scientific publication. Further research is necessary to evaluate pain threshold in aerobic exercise modalities.