Diverse characters of Brennan’s paw incision model regarding certain parameters in the rat

Abstract

Background Brennan’s rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. Methods Separate groups of Sprague–Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and 10 μg of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. Results COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. Conclusions Based upon current observations, Brennan’s rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions

“…The expression of SSTR 4 is upregulated in inflammatory models ( 53 ), and activation can inhibit inflammation induced by either mustard oil or lipopolysaccharide ( 10, 54, 55 ). In response to injury, inflammatory responses are generally observed within 2 h ( 56, 57 ). SSTR 4 -mediated inhibition of inflammation could help explain the seemingly longer-lasting effect of Fj1 compared to morphine, where the later stage effect might, in part, be due to a reduction in the post-injury inflammatory response that would otherwise hypersensitize the pain response ( 58 ).…”

A novel excisional wound pain model for evaluation of analgesics in rats

“…The most commonly used model is the Brennan model, which involves an incision on the hind paw in the skin and fascia and sometimes muscle, followed by suturing. This model has been widely used for the evaluation of pathophysiological mechanisms of wound pain [ 26 ] and post-surgical analgesic options [ 27 , 28 ]. The pain behaviors tested in the Brennan model show statistically significant differences only for up to 72 hours post-wounding, which is a limitation in evaluating the duration of action of extended-release analgesics [ 29 , 30 ].…”

The mechanisms and management of persistent postsurgical pain

“…Beyond the nociceptive response, other physiological parameters such as inflammation, are monitored postoperatively in patients and could be back translated in preclinical models. Changes in inflammatory mediators in the wound vicinity have only recently been reported in the Brennan model, i.e., increased COX-2 activity and leukotriene B4 levels after incision ( 150 ). Furthermore, protein C, which is a natural anticoagulant, displayed antinociceptive activity (attenuation of guarding score) when injected into the wound and is a possible mediator of pain at rest after surgery in patients ( 150 ).…”

“…Changes in inflammatory mediators in the wound vicinity have only recently been reported in the Brennan model, i.e., increased COX-2 activity and leukotriene B4 levels after incision ( 150 ). Furthermore, protein C, which is a natural anticoagulant, displayed antinociceptive activity (attenuation of guarding score) when injected into the wound and is a possible mediator of pain at rest after surgery in patients ( 150 ). Unbiased proteomic approaches to studying postsurgical pain are also helping to bridge the translational gap by identifying protein-protein interactions at the incision site that differ between human and mouse ( 151 ).…”