Predicting post-operative pain: Still a long way to go!

There have been tremendous advances in understanding the physiology, signaling pathways and biochemical transmission of pain in the last two decades. This has resulted in novel medications for alleviating pain (COX-2 inhibitors etc.) and alternate drug delivery routes (neuraxial, intra-articluar, transdermal). However, post-operative pain continues to be under treated.[1234] One of the important reasons for this is individual variation in pain perception and tolerance. Post-operative pain could be better managed if the anesthesiologists or pain physicians could predict the “quantum” of pain not only for different types of surgeries but also for individual patients. One of the areas of interest and research for all physicians dealing with pain relief is the prediction of intensity of post-operative pain. If possible, individualized post-operative pain management strategies could be “tailor made” for patients with low thresh-hold for pain. Not only this would make the patient more comfortable but would decrease the incidence of all disorders associated with over or under treating pain.

The challenge in segregating patients who will experience more post-operative pain or who would require larger doses of analgesics is that the risk factors for perioperative pain include not only quantitative sensory measures but also psychosocial, gender related and genetic factors.[5678910]

A recent review has concluded that there are four important factors that can have prediction value regarding intensity of pain in the post-operative period. These are - anxiety, pre-existing pain, age, and type of surgery. Factors predicting the quantity of analgesics required are - type of surgery, age, and psychological distress.[11] Awareness about these factors and their early identification can result in optimal pain management. However, individual variations still exist among patients in each of the above mentioned categories.

In an effort to find such patients that would require special, intensive treatment of their post-operative pain, experimentally induced pain has been used to predict post-operative pain intensity. Werner et al. in a review on pain prediction inferred that though pain perception was a complex issue, pre-operative quantitative sensory testing may be a “clinically relevant predictor of post-operative pain.” The authors also reported that pre-operative sensory tests could predict up to 54% of the variance in acute post-operative pain across individual patients.[12] The experimentally induced pain in patients is usually produced by three ways: Extremes of temperature, high pressure or by mechanical injury.[131415]

The most studied and validated of the above techniques is the use of increasing temperature to produce pain. Pedersen et al. showed a correlation between the pre-operative electrical pain thresholds and post-operative opioid consumption after percutaneous nephrolithotomy. They hypothesized that measurement of electrical pain thresholds in the pre-operative period could be used as a screening tool to identify patients at high risk of post-operative pain after percutaneous nephrolithotomy.[16] Similarly, Rago et al. used a sphygmomanometer cuff to produce a pressure of 250 mm Hg for assessment of pain tolerance and correlated this with pain scores and analgesic requirements after thyroidectomy.[17] Pain induced by electrical stimulation was used by Nielsen et al. for similar prediction regarding post-cesarean pain.[18] However, all the above modalities would need extra-equipment and trained manpower to conduct the prediction tests.

In this issue “Pre-operative pain sensitivity – a prediction of post-operative outcomes”, the authors[19] have tried to correlate pressure and electrically induced pain a day before surgery with the pain scores and morphine requirements (administered through intravenous patent controlled analgesia) in 20 parturients undergoing elective cesarean sections. The authors have reported a significant correlation between pre-operative electrical pain threshold, and pressure pain threshold with morphine requirements in the post-operative period. As mentioned in the article by the authors the study sample is too small to accept this correlation as very useful so that the testing could be made a routine practice. Research on such a correlation has been carried out for a long time but a clinically useful correlation has evaded the researchers so far.

In a recent study, Carvalho et al. have tried correlating labor pain with experimentally produced pain and pain caused at the time of intravenous cannulation. Only the latter was reported to have some prediction value for the time of need of epidural analgesia.[20]

Pain sensations due to experimentally produced pain with extremes of pressure or temperature travel via C type of fibers through the lateral spinothalamic tract into the thalamus. It must be realized that experimentally induced pain may not correlate very strongly with surgical pain as surgical stimulus arising from skin traverses via A-delta type fibers and via the thalamus into a different parietal center. Thus, the whole hypothesis that experimentally produced pain would simulate surgical pain may not be true. The two may parallel only by logical basis but for example in patients with sympathetic system disorders like complex regional pain syndrome (CRPS) only C-type fibers cause pain, whereas A-delta fibers may be normal; though, CRPS is a chronic condition, unlike post-operative pain. Until well planned studies on a large number of patients actually prove this correlation, using experimentally induced pain as a measure of post-operative pain may not be justified. Although the above approach of simulating surgical pain, measuring it and eventually finding the magic doses for treating pain in patients who have low thresh hold of pain is a novel idea but a lot needs to be learnt before clinical use of these tests can be advocated.