Following provision of a signed consent form from each subject, a total of 120 subjects were enrolled in the study. Subjects were randomly divided into two main groups (group A and group B), and each group consisted of three subgroups (A1, A2 and A3, and B1, B2 and B3, respectively). Sixty participants from each group were equally divided into three subgroups (n = 20). Group A patients received analgesics both pre-operatively and post-operatively. Group B patients received drugs post-operatively only. Subgroups 1, 2 and 3 were prescribed Paracetamol, Ibuprofen and Mefenamic Acid, respectively. Visual Analog Scale (VAS) was used to evaluate the patients’ post-extraction pain until 56 hours at every 8-hour interval (Table 1). Evaluation of pain just after extraction was considered ‘0’ hour.

Table 1

Pain severity	Scale
No Pain	0
Mild Pain	1-3
Moderate Pain	4-6
Severe Pain	7-9
Worst Pain	10

Data were analyzed using Pearson chi–squared ( χ2) test (SPSS version 22) and the significance level was set at p < 0.05.

Among the patients who received analgesics pre-operatively (Group A), 26 reported no post-extraction pain at ‘0’ hour while only 3 reported severe pain. However, in Group B which received analgesics post-operatively only, 10 patients recorded no pain while 5 developed severe pain (Table 2). Further analysis showed a significant difference (p = 0.0045) between pre- and post-operatively treated groups in post-extraction pain control at ‘0 hour’.

From cumulative and periodical evaluation of post-extraction pain until 56 hours, it was observed that the total number of times pain was reported by patients of Group A was lower than that of Group B. Only for 9 times did patients of Group A report severe pain, which was reported 18 times for Group B (Table 3). However, no significant difference (p = 0.151) was observed between pre- and post-operatively treated cohorts with respect to post-extraction pain control out til 56 hours.

Table 3

Pain Scale	Group A	Group B
0 No Pain	227	216
1-3 Mild Pain	134	122
4-6 Moderate Pain	51	64
7-9 Severe Pain	9	18
10 Worst Pain	0	0

Among the three medications taken in this study to evaluate pain reduction efficiency, patients with severe post-operation pain due to severe inflammatory conditions responded well with Mefenamic Acid, and followed by Ibuprofen; the lowest response was observed for aracetamol administration (Table 4).

Table 4

Scale	Group A			Group B
	A1	A2	A3	B1	B2	B3
0 No Pain	9	8	9	3	4	3
1-3 Mild Pain	6	7	7	6	7	7
4-6 Moderate Pain	4	3	4	10	7	8
7-9 Severe Pain	1	2	0	1	2	2
10 Worst Pain	0	0	0	0	0	0

Post-operative pain alters or sometimes halts the normal activities of the patient, and increases suffering and anxiety. It disturbs the homeostasis of the endocrine and circulatory systems. Moreover, post-operative pain negatively influences the wound healing process12, 13. Hence, reliable and fast-onset analgesia is highly needed. This study was designed to test the currently popular belief that pre-operative measures are helpful in the prevention or modification of post-operative pain.

Even though several studies have been done on various aspects of pain management, pain remains the most sensitive and predominant issue from both the doctors’ and patients’ point of view. Many studies have been conducted on understanding the management of post-operative pain by various means of pre-operative methods, collectively referred to as pre-emptive analgesia. Prescribing analgesics to patients prior to dental treatment has proven to provide better pain control than post-operatively in many studies. In this study, we have also observed that analgesics used prior to teeth extraction have better effects on post-extraction pain control.

Immediately after any surgery, central sensitization induces excitability in the central nervous system14. In the head and neck region, inhibition of central sensitization is limited. In contrast, various post-surgical noxious inflammatory stimuli may continuously stimulate local nociceptors and induce peripheral sensitization14, which may increase the excitability of dorsal horn neurons and eventually could cause central sensitization15. Following establishment of central sensitization, patients respond poorly to analgesics16. The surgeries that are linked to the strong post-surgical inflammatory reactions usually cause sensitized severe post-operative pain. Hence, the concept of pre-emptive analgesia is introduced to prevent central sensitization before surgery to help minimize post-operative pain17.

Several randomized control studies have shown the post-operative pain inhibitory potential of pre-operative non-steroidal anti-inflammatory drugs (NSAIDs) in tooth removal. In this study, we have also observed significantly less experience of acute pain following extraction in those patients who took analgesics pre-operatively. This could be because of the inhibition of central sensitization that results from tissue damage during removal of the impacted tooth and the inhibition of peripheral sensitization that results from inflammation following tooth removal. In this study, only a few patients developed severe pain in the pre-operative group which could be due to secondary infections in patients not following the instructions or maintaining poor oral hygiene.

Post-operative pain is a common complication following extraction. In our study, patients prescribed with analgesics prior to dental treatment reportedly experienced lower pain level post-treatment as compared to patients prescribed only post-operatively. The types of analgesics in our study, namely Paracetamol, Ibuprofen and Mefenamic Acid, affect the post- operative pain differently. Though there were no significant differences in efficacy among the analgesics used in this study, Ibuprofen and Mefenamic Acid showed better anti-inflammatory properties compared to Paracetamol and, thus, in reducing pain levels post-operatively as well.

On the basis of the results of this study, we can conclude that in dental extraction cases, use of pre-operative analgesics may help to attenuate central sensitization while post-operative peripheral sensitization could be inhibited by administering post-operative analgesics. Moreover, this preventive analgesia method could be most effective method in controlling post-operative pain in other dental surgeries as well. Hence, for dental extractions and minor oral surgical procedures, analgesics should be given pre-operatively to mitigate post-operative pain and to reduce post-operative pain medication dosage requirement, thereby supporting a better healing process.

COX: Cyclooxygenase

CNS: Central Nervous System

H0: Null hypotheses

H1: Alternative hypotheses

NSAIDs: Non-steroidal anti- inflammatory drugs

PCM: Paracetamol

Post-op: Post-operative

Pre-op: Pre-operative

t.i.d.: ter in die, three times daily

The authors would like to thank the Staff Nurses from Oral and Maxillofacial Surgery Department, supporting staffs from dental clinic and all year 5 students of 2017-2018 batch, Faculty of Dentistry, MAHSA University; and all supporting staffs from MAHSA Dental Clinic, Jalan Dang Wangi for their support in this study.

GPK conceptualized and designed the work. CSL, GEW, LWS and NFKL carried out the experiment. GPK and NH conducted formal analysis. GPK, CSL, GEW, LWS, NFKL and NH prepared the original draft. GPK and NH reviewed and edited the drafts. All authors read and approved the final manuscript.

Not applicable.

The basic clinical data used to support the findings of this study are included within the article. The data used to support the findings of this study are restricted in order to protect patients privacy, but available from the corresponding author upon request. (To contact Dr. G. Padmanabha Kumar drgpk1@gmail.com)

This study was conducted in accordance with the amended Declaration of Helsinki. The institutional review board approved the study, and all participants provided written informed consent.

Not applicable.

The authors declare that they have no competing interests.