Pain is a part of all orthodontic treatments [1, 3, 9, 14, 33], although its intensity, prevalence, and duration are disputed [1–7, 9–14, 16, 33–37]. About 90 % of patients experience pain during fixed orthodontic treatment [1–7, 11, 14]. In this study, all patients firstly felt pain in the first 24 h, which although decreased significantly, did not completely eliminate within 1 week. This was in line with earlier studies [1–3, 5, 6, 9, 16], most of which asserting that the pain peaks within the first 24 h and lasts for a short period [2, 5, 11–14, 33–35], while some others state that it might last for a rather long duration [6, 16]. Although not completely understood, orthodontic pain is mainly attributed to the compression of periodontal ligament under orthodontic forces [2, 7, 12, 14]. The immediate response to orthodontic forces characterizes by ischemia and PDL compression. After a few hours of prostaglandin release, the sensitivity of the pain receptors to noxious chemicals (e.g., histamine, bradykinin, acetylcholine, etc.) increases, marking the PDL hyperalgesia phase. This mechanism together with other phenomena (such as osteoclastic activity, neurogenic inflammation, and vasodilatation in the PDL) might cause pain [2, 3, 5, 7, 12, 14, 16, 35]. Different methods proposed to reduce orthodontic pain are NSAID consumption, chewing plastic wafers or gum, vibratory and transcutaneous electrical stimulation, and a diet of softer foods [7, 11, 15, 16]. It seems that fixed appliances might cause higher levels of pressure, tension, pain, and sensitivity of the teeth compared to removable appliances [13, 38]. However, the differences between the levels of pain treated with various fixed appliances such as with self-ligation, lingual, or conventional brackets were mostly not significant [33, 38, 39]. Recently, Invisalign approach has been suggested as a less painful method, although it has its own limitations .
Low-level laser therapy can be performed by He-Ne lasers. Irradiation with He-Ne laser at 632.8-nm wavelength and energy of 7.5 J/cm2 might reduce inflammation and accelerate the healing . In this study, a single dose of He-Ne laser was shown effective in reducing the orthodontic pain sensed after beginning of tooth movement. There was no previous study on this particular type of laser, and all studies focused on laser wavelengths longer than ours. Therefore, we are limited to compare these results with other laser types. In this study, laser treatment contributed to about 12.1 % pain reduction in the laser side compared with the matched placebo side (1.21 out of 10 points). Our result was within the range reported in split-mouth studies [19, 26, 41] while it was smaller than the differences observed in parallel designs [18, 21, 42]. Of the few split-mouth studies conducted in this regard, only two found a significant difference. In one of them, laser irradiation accounted for 36.7 % pain reduction (3.67 out of 10) , while in the other one, laser reduced orthodontic pain for a statistically significant main score of 6.4 % (0.64 score out of 10) favoring laser irradiation . The other two split-mouth designs failed to find a significant difference with very small differences (0.6 % in favor of the placebo side  and 2.4 % in favor of laser ). On the other hand, all parallel designs showed significant differences between the laser and placebo groups, with differences ranging from 19.6 to 52.5 % all favoring laser groups [18, 21, 42–44]. The differences can be attributable to the highly different methodologies including the orthodontic technique applied, laser dosimetry and parameters, the number of laser irradiation sessions, the laser types used, sample sizes, age ranges, gender compositions, analgesic consumption, and many other factors . Mechanisms responsible for the pain-reducing effect of LLLT are unclear . Perhaps, because of having anti-inflammatory and neural regenerative properties—as a probable result of photobioactive reaction which stimulates cell differentiation and proliferation—low-level laser therapy might be useful for pain control [20, 42–46]. Also, it might improve blood supply and enhance tissue recovery [42, 47]. Other factors contributing to the analgesic effect of LLLT might be the reactivation of enzymes targeted at pain-inductive factors, inhibiting nerve depolarization (C fibers in particular), ATP production, and prostaglandin reduction [15, 48]. Also, LLLT might alter nerve conduction by influencing the synthesis, release, and metabolism of encephalin and endorphins and many other neurochemicals [15, 49].
Limitations and strengths
This study was limited by some factors. Pain is subjective, and numerous factors (such as sex, age, genetics, pain threshold, stress, emotional state, response to analgesics, sociocultural differences, past pain experiences, and the magnitude of the force applied) can affect it [1, 2, 4, 5, 7, 9, 11, 14–16, 30, 46, 32]. On the other hand, the sample size was based on a pilot study and the post hoc power was very high because of the specific design of the study, excluding the abovementioned confounding variables [30, 50]. Moreover, VAS is understandable by patients and is reliable, sensitive, and reproducible [5, 11, 12, 14, 16, 46]. Still, standardizing the intolerable pain was virtually impossible, as patients might have different levels of tolerance to pain. However, this could favor the generalizability since it was similar to what happens in a clinical condition, as what is relevant to patient is not a pain which can necessarily keep them awake at night (as might be incorrectly considered as a standardized response), but a pain which can render that specific patient seek emergency treatment.
Some studies did not exclude patients taking analgesics and only monitored the number of analgesics taken . However, taking analgesics could disrupt the reliability and validity of the responses [30, 32]. Therefore, this and some other studies [21, 23] excluded such patients. Since there was no bias in delivering proper treatment towards the excluded patients and patients had voluntarily participated, they were unlikely secretly taking painkillers while falsely reporting the opposite. Therefore, the pain-related side effects might not be biased. It was possible that excluding patients consuming analgesics might skew the sample to more cooperating and psychologically prepared patients (and perhaps also to those with lower pains) . However, including patients taking analgesics would not help in improving the generalizability, since they would as well perceive lower pains and skew the results . Finally, the inclusion of both genders and a rather broad range of ages favored the generalizability, as pain perception might differ between ages [7, 16] and between genders [1, 3, 7]. The role of age in pain is debated, since the methodologies differ , and the correlation between pain threshold and age might be non-linear [7, 16]. There might be a linear negative correlation between general pain and age until the age 25 years [14, 16]. Nevertheless, in orthodontics, the relationship is not necessarily linear, and the most sensitive age might be between 13 and 16 years old [7, 14]. Some studies have observed more intense pains in older subjects [3, 14, 36] while some others have found no correlations between pain and age [12, 16, 33]. Besides sample and methodological differences, this again might be caused by a non-linear correlation pattern, with adolescence or another age range having lower pain thresholds compared to ages younger or older than it [7, 16]. With this in mind, enrolling subjects from different ages seem advantageous over pooling a narrow age range, since results of a study on pain in children might not be necessarily generalizable to pain perceived by adults and vice versa. Since, in this split-mouth design each subject was matched with himself/herself, such variations in patients’ demographics less likely confound the results, since the laser (treatment) sides were perfectly matched with their counterpart placebo quarters, in terms of age, gender, genetics, etc.