Psychology

History and development
Pain is the unpleasant sensory or emotional experience associated with strong emotional responses with ensuing physiological and psychological changes (Wilson, Grande and Hoyt, 2007). Due to this, administration of analgesics and sedatives has been widely used even though the effect of these drugs is sometimes delayed and may compromise the safety of the patient. However, provision of clinical approach to analgesia gave more optimal pain management prior to analgesics and sedatives used (Wilson, Grande and Hoyt, 2007).

Preemptive analgesia is the process initiated prior to an acute nociceptive stimulus, either by surgery or injury, to prevent the sensitization of the central nervous system (Cousins and Bridenbaugh, 2009). To simplify it, it is a method of pain control that aims to reduce the initial intensity of pain and thereby prevent the development of persistent or neuropathic pain syndromes (Wilson, Grande and Hoyt, 2007). Apart from the relief offered to patients, there are expected functional benefits that can be associated with an effective analgesic therapy.    In addition, preemptive analgesic approaches also recognize that acute painful events can lead to long-term painful consequences, where in pain persists even when tissue healing appears to be complete. This long term changes in pain reduction motivated the use of preemptive analgesia (Fleisher, 2009).

Through developments, the term preventive analgesia has been applied to clinical and laboratory studies to demonstrate a beneficial effect of an analgesic intervention that outlasts the pharmacological presence of the intervention (Fleisher, 2009). Studies defined this manner by a typical administration of identical analgesic interventions at different times to test and control groups, where typical times would be pre-incision and post-incision or preoperatively and postoperatively (Fleisher, 2009). The concept of preemptive analgesia was first proposed by Dr. George Crile in 1913, a surgeon who advocated the use of nerve blocks to supplement general anaesthesia to prevent painful wound scars (Cousins and Bridenbaugh, 2009). It originated at a time of growing appreciation for the dynamic characteristics of the pain pathway through different experimental studies, which appeared to demonstrate that subjects who underwent surgery experienced less postoperative pain and raised the possibility that preemptive analgesia has prolonged effects, which outlast the presence of drugs (Fleisher, 2009). Since then, preemptive analgesia became an important conceptual step because it integrated both the notion of preventing pain before it occurred as well as the possibility that acute events could influence long-term pain (Cousins and Bridenbaugh, 2009). In the widest sense, it recognizes the noxious stimuli at any point throughout the entire perioperative period to sensitize the nervous system (Fleisher, 2009).

Identification of neurophysiologic mechanisms stimulated modern clinical interest when laboratory research demonstrated a reduction in central hypersensitivity and plasticity when analgesic drugs were administered prior to the imposition of a nociceptive stimulus (Cousins and Bridenbaugh, 2009).
In order to be most effective, preemptive analgesia strategies must interact at all sites of unreceptive input into the spinal cord. Thus, wound infiltration with local anaesthetics will not block inputs from deeper structures, and epidural analgesia neither may nor block all relevant dermatomes or autonomic nociceptive pathways (Cousins and Bridenbaugh, 2009). Importantly the period of intense nociceptive input may continue well into the post procedural period and heightened by peripheral hypersensitivity (including inflammatory processes) (Cousins and Bridenbaugh, 2009). Thus, the treatment used should extend in time to cover this stimulus as well. To achieve this level of control of central sensitization is very difficult in clinical practice, which explains why the treatment effect seen in many studies is small or absent despite encouraging laboratory work. Seeking out strategies for preemptive analgesia has a broader justification because of the significant growth in recognition of persistent or chronic pain following surgical procedures (Cousins and Bridenbaugh, 2009). Central sensitization at the time of surgery may contribute to both the degree of acute postoperative pain and the likelihood of chronic neuropathic pain (Cousins and Bridenbaugh, 2009).

Techniques and methods
One of the most critical observations concerning central sensitization is the role played by the first phase of the pain response. Preemptive analgesia strategies have involved interventions at one or more sites along the pain pathway (Gottschalk and Smith, 2001). Examples of preemptive analgesic techniques include the use of anesthetic premedication such as opiods, alpha agonists, and NSAIDs, or the presurgical epidural administration of local anesthetics or opiods (Tranquilli, Grimm and Lamont, 2004) as well as  nerve block, epidural block, subarachnoid block, intravenous analgesics and anti-inflammatory drugs (Gottschalk and Smith, 2001). Opiates administered before the first phase and reversed with the opiate antagonist naloxone before the expected onset of the second phase were capable of preventing this late stage of the pain response (Gottschalk and Smith, 2001). It acts primarily at pre- and postsynaptic receptors present in the peripheral and central nervous system (Tranquilli, Grimm and Lamont, 2004) and that venous infusion of opiods may also decrease morbidity and mortality rates in patients (Fleisher, 2009). Also, intravenous opiates or ketamine administered before incision can lead to decreases in wound hyperalgesia days after the surgery anti-inflammatory drugs may play an important role in perioperative pain management by reducing the inflammatory response in the periphery and thereby decreasing sensitization of the peripheral nociceptors. This should help attenuate central sensitization (Gottschalk and Smith, 2001). Local anesthetics, on the other hand, prevent conduction of nerve impulses by inhibiting passage of sodium ions through ion-selective channels in nerve membranes (Tranquilli, Grimm and Lamont, 2004). For example, infiltrating the incision site with the long-acting local anesthetic bupivacaine after administering general anesthesia and before incision was found to be more effective for hernia repair pain than either spinal anesthesia or general anesthesia alone, and these benefits appeared to last many days (Gottschalk and Smith, 2001). Meanwhile, alpha 2 adregenic agonists are found in similar regions of the brain and even on the same neurons (Tranquilli, Grimm and Lamont, 2004).

Surgery can be an example of a clinical setting where preemptive analgesia techniques will be most effective because the onset of the intense noxious stimulus is known (Gottschalk and Smith, 2001). To appreciate the design of clinically effective strategies in this setting, it is essential to recognize that otherwise adequate levels of general anesthesia with a volatile drug such as isoflurane do not prevent central sensitization. Other techniques such as intrathecal and epidural techniques in patients undergoing cardiac surgery offers three potential clinical benefits, where it enhances postoperative analgesia, stress response attenuation and thoracic cardiac sympathectomy (Fleisher, 2009). Thus, the potential for central sensitization exists even in unconscious patients who appear to be clinically unresponsive to surgical stimuli (Gottschalk and Smith, 2001).

Another example of technique for perioperative pain control involves the use of an epidural catheter (Gottschalk and Smith, 2001). These catheters are usually placed at a lumbar or thoracic interspace before the start of major thoracic, abdominal or orthopedic procedures and can be maintained for several days to provide postoperative analgesia. Typically, local anesthetics and opiates, alone or in combination, are administered through the epidural catheter as an infusion or a bolus to provide analgesia (Gottschalk and Smith, 2001). In some animal experiments, the benefits of preventing central sensitization were demonstrated by infiltrating with local anesthetics, an approach that was particularly effective with pain associated with differentiation, as might occur with amputation (Gottschalk and Smith, 2001). Collectively, results like these led to the concept of preemptive analgesiainitiating an analgesic regimen before the onset of the noxious stimulus to prevent central sensitization and limit the subsequent pain experience (Gottschalk and Smith, 2001).

Many clinical protocols have mirrored the laboratory studies using animals that gave birth to the concept of preemptive analgesia. However, these animal experiments employed painful stimuli of intensity, duration and somatotropic extent that were generally far less than that experienced during even relatively minor surgery in human patients (Gottschalk and Smith, 2001). Analgesic strategies for more extensive procedures require interventions capable of preventing central sensitization throughout the perioperative period and, therefore, require a commitment from the entire surgical team (Gottschalk and Smith, 2001).

Ultimately, multimodal approaches that address multiple sites along the pain pathway may prove necessary to adequately prevent central sensitization in many surgical procedures (Gottschalk and Smith, 2001). Preemptive analgesia have also been likely being employed to children who undergo circumcision to achieve a much better post operatively and require less analgesia (Hadidi and Azmy, 2004) it also showed that less vomiting and nausea troubles has been observed in patients. Also, increasing evidence has also shown that the trigger for chronic pain of the neuropathic type is more common of the painful stimulus is not controlled during surgery. Therefore, it will be a good practice to establish a good neurological block prior to the commencement of each and every surgery (Hadidi and Azmy, 2004).

Cases and Efficacy
There are many studies performed in order to assess the efficacy of preemptive analgesia. In evaluating its clinical trials, the timing of the intervention is only one factor. It is also essential to consider the ability of the intervention to prevent central sensitization and whether other aspects of the perioperative pain experience may be of sufficient duration and intensity to mask any intraoperative benefits from the preemptive analgesia (Gottschalk and Smith, 2001). Theoretically, immediate postoperative pain may be reduced and the development of chronic pain may be prevented through pre-emptive analgesia is defined as the treatment that is initiated before the surgical procedure in order to reduce this sensitization, which therefore presumed that pre-emptive analgesia has the potential to be more effective than a similar analgesic treatment initiated after surgery (Dahl and Moiniche, 2004). Presently, the effect of the preemptive analgesia remains controversial due to some studies that did not show the same effectiveness and efficacy of this procedure. However, certain studies have shown results on the efficacy of preemptive analgesia.

One of the earliest studies of Gottschalk and Smith, 2001, the efficacy of preemptive epidural analgesia involved lower extremity amputation. Patients in the intervention group received several days of epidural analgesia for their painful lower extremity before receiving epidural anesthesia during surgery. This was followed by several days of postoperative epidural analgesia. In the control group, the amputation was performed with epidural anesthesia, and patients received intravenous and oral opiates for analgesia. One year after surgery, the intervention group demonstrated dramatic reductions in phantom limb pain, stump pain and phantom sensation when compared with the control group. However, even the control group experienced one-year postoperative phantom limb pain at one half of the historical rate of 70 percent, presumably because performing the amputation with regional blockade limited central sensitization.

A study was performed to determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. 100 healthy patients were scheduled for the process and were administered with epidural bupivacaine, epidural fentanyl and others were not administered with drugs prior to induction of anaesthesia. The results have come up with a significant reduction of postoperative pain during hospitalization to patients and long after discharge (Gottschalk et.al., 1998). According to the study performed by Ong, Lirk, Seymour and Jenkins in 2005, wherein they systematically searched for randomized controlled trials to compare preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. 3261 patients were analyzed in the study and showed a significant result on the efficacy of preemptive analgesia. The results have shown an overall beneficial effect after epidural analgesia, local wound infiltration, and systemic non-steroidal anti-inflammatory drug administration. On the other hand, a comparative study was made by Shen et.al.in 2008 to investigate the analgesic efficacy of tramadol administered preemptively or preventively in the earlier period of lumpectomy. Four hundred (400) anesthesiologists were screened and about 317 of them were randomly assigned into groups of preemptive tramadol and preventive group. The result of the study showed similar efficacy between the two groups, which implied the administration of tramadol either before the start or before the end of the surgical procedure could produce an effective postoperative analgesia in patients. On the study of Wang, Shen,  Xu, and Liu in 2009 where they investigated a controlled trial of 224 patients undergoing elective abdominal hysterectomy.

The subjects were divided in to two groups, the tramadol group in which they are given tramadol 30 minutes before the operation and the control group whom received only an equivalent volume of normal saline. The results of the study showed that having tramadol 30 minutes before the operation improves analgesia and reduces nausea, dizziness and drowsiness when compared to the same analgesic regimen that omitted the preemptive tramadol. Based on the study of Lee et.al., al. in 2008, which aimed to determine the analgesic effect of parecoxib when administered either before or at the end of the surgery in patients undergoing colorectal laparotomy. The study randomly grouped 60 patients, where 1 group received 40mg of parecoxib before skin incision and normal saline at skin closure, and the other group received saline before skin incision and intravenous parecoxib 40mg at skin closure. Control group received saline both time points. The results showed that parecoxib administration at the end of surgery is as effective as at the beginning with regard to analgesic and opiod-sparing effects. On the other hand, two cases were reported by Topfner et.al. in 2001 who investigated the efficacy of pre-emptive analgesia for phantom limb. Two cases of traumatic amputations were described in the study with no pre-existing pain. Both of the patients received antinociceptive treatment by continuous block of the brachial plexus through infusion of ropivacaine 0.375 at 5mlh for 10 days. Treatment of case 1 was initiated immediately after surgery however, this amputee developed intensive phantom limb pain which persisted at 6 months.

On the other hand, the limb pain of the second patient limb pain in case 2 decreased significantly after 6 months, even though brachial plexus blockade was not started until 5 weeks post-trauma. This patient used a functional prosthesis intensively beginning early after amputation. Only case 2 showed significant changes of cortical reorganization. In case 1 markedly less cortical plasticity was found. A combination of relevant risk factors such as a painful neuroma, behavioural and cognitive coping strategies and the early functional use of prostheses are discussed as important mechanisms contributing to the development of phantom pain and cortical reorganization. Such case can be an example of the controversy of the procedure that it can be effective in not all cases. However, having preemptive analgesia before and after an operation can possibly neither decrease nor reduce the pain of a patient. Factors such as right timing in applying analgesia in patients can also affect the affectivity of the said method.