A New Rodent Model of Hind Limb Penetrating Wound Injury Characterized by Continuous Primary and Secondary Hyperalgesia

This article reports the development of a new hind limb pain model in which an incisional stab wound is placed on the front and back of the calf, causing both superficial and deep tissue injury. The injury causes primary mechanical hyperalgesia on the calf and secondary hind paw hyperalgesia, which served as the focus of the present study. Animals with unilateral stab wounds showed a significant increase in percent paw withdrawal (secondary mechanical hyperalgesia, reversed by morphine administration) from 2 to 48 hours after surgery, but no evidence of thermal hyperalgesia. In contrast, animals with bilateral leg injuries showed bilateral secondary mechanical and thermal hyperalgesia. Rats with unilateral leg incisional stab wounds showed a significant decrease in cage activity in both the horizontal and vertical directions, monitored by using a novel activity box approach, as compared to their 24-hour baseline levels or to the activity of naïve animals. Analysis of spinal cord Fos labeling demonstrated that calf injury significantly increased Fos expression in laminae I to VI of the L3-L5 cord segments. The data indicate that this model might be useful for evaluation of the mechanisms underlying penetrating injury-induced primary and secondary hyperalgesia or for testing the effect of analgesics on hyperalgesia induced by such injury. Perspective: Stab wounds and other types of penetrating wounds routinely encountered in emergency rooms and clinics are accompanied by pain associated with superficial and deep tissue injury. Here we present a rodent stab wound model that affords an opportunity to study the mechanisms of pain associated with traumatic injury.