INCISIONAL pain mechanisms have been studied systematically for the past 10 yr, increasing the interest in the pathophysiology of postoperative pain.1In this issue of Anesthesiology, Duarte et al. 2rigorously examined responses to mechanical stimuli after an incision on the dorsum of the rat hindquarters. The study contributes to our understanding of incisional pain mechanisms because hairy skin was incised and the manner in which the model was tested was unique.
Postoperative Pain Measurements
In humans, we have used a variety of methods to quantify pain generated by surgery (table 1, left). After abdominal surgery, we typically obtain pain scores at rest, with ambulation and perhaps during cough.3The same measurements might apply to patients undergoing thoracic surgery in which the pain during cough has been linked to outcome.4After total knee replacement, pain measurements at rest and during flexion are typical, and greater range of motion in the first few days after surgery is associated with greater function weeks later.5A goal of a perioperative analgesic regimen (e.g. , continuous femoral nerve blockade) is to achieve a greater degree of flexion with less pain and fewer opioid-related side effects. In clinical studies, under the best circumstances, the measurement is related to outcome for the surgical procedure (e.g. , rehabilitation after knee replacement).
Other pain tests have been explored in patients to attempt to understand sensitization and further quantitate postoperative pain. One of these tests is punctate secondary hyperalgesia, usually mapped or quantified by a small punctate mechanical stimulus applied outside the area of an incision, e.g. , after nephrectomy6or colectomy.7In some cases, the force required to provoke pain after surgery is quite small, indicating that a touch stimulus has been converted to pain by the surgery.6This remote hyperalgesia is secondary because the test site is outside the area injured by the incision, the area of primary hyperalgesia. Central nervous system sensitization causes pain in the secondary zone because the sensory fibers function normally outside the area of injury.8
Other methods, in addition to the area of hyperalgesia outside the injury, have been used to quantify postoperative pain. In one study of pediatric patients, the primary punctate force for the abdominal flexion reflex was measured in children after herniorraphy.9A week force provoked a flexion response after surgery, and the response magnitude was increased as well. Using a different mechanical test after hysterectomy, a blunt probe was applied near or distant to the incision, and the pressure pain threshold that evoked pain was recorded.3Again, a widespread area of sensitivity could be measured and this persisted for up to 1 week after surgery. These tests have the advantage in that the stimulus intensity can be quantified. In clinical postoperative studies, analgesics must be available as needed, and therefore, superimposed on pain scales and pain measurements is analgesic consumption, which may confound the detection of a novel treatment. Furthermore, a problem with some evoked pain measures, such as pain during cough, is that there is difficulty standardizing effort.
Postincisional Pain Measurements in Animal Models
Previous studies using incisional pain models (table 1, right) have used nonevoked guarding behavior, punctate mechanical withdrawal threshold, a distant secondary mechanical withdrawal threshold, heat withdrawal latency,10,11and weight bearing12,13to measure pain-like responses. In addition, locomotor activity, rearing, and conditioned responses have been used after experimental laparotomy.14,15The study by Duarte et al. 2examined several new tests for pain after a hairy skin incision (table 2). First, the intensity of the response was measured, rather than an “all-or-none” response. Second, the responses were separated into allodynic-like and hyperalgesic-like responses based on careful characterization of the stimuli. Finally, in this model, the regions of primary and secondary hypersensitivity are easily distinguished, and these have distinctive time courses and unique responses to treatments. Profound plasticity, an area of intense interest to pain research, is evident in the secondary zone. The precise clinical role of these sensitization phenomena, primary (injured territories) and secondary (uninjured territories) responses, and postincisional hyperalgesia and allodynia, are not yet understood, as noted by the authors.
A challenge for research in postoperative pain mechanisms and for pain research in general is to quantify exaggerated nociceptive responses in both patients and nonhuman models, even though the clinical state, the experimental model, and the tests may not be precisely the same among species. From the preclinical models, mechanisms will be understood, and from the patients, clinical relevance of these tests and treatments that affect the exaggerated processing will be ascertained.
The University of Iowa, Iowa City, Iowa. firstname.lastname@example.org