Guarding pain and spontaneous activity of nociceptors after skin versus skin plus deep tissue incision.

IN pain research, the pathophysiology of sensitization that produces allodynia and hyperalgesia in postinjury states has generated considerable interest. Ongoing, unprovoked pain after injury is less well studied. In patients with postoperative pain, this is measured as pain at rest, which should be transmitted by spontaneous activity (SA) from nociceptors. Generally, most nociceptors have no SA, and the generation of SA in postinjury states is perhaps the most powerful form of sensitization in nociceptive pathways. Several investigators have used needles or scalpels to injure the receptive field (RF) of skin nociceptors but did not generate SA, even though marked ongoing pain would be expected immediately after acute injury.1–3 To better understand postoperative pain, we have examined a variety of pain-related behaviors and explored the underlying mechanisms for postoperative pain using an incisional pain model.4 Unprovoked pain-related behavior, guarding, after rat plantar incision has been described and suggested to be a correlate to the pain at rest in patients.4–6 For example, pain at rest after surgery is greatest in the recovery room7 and on the first few days after surgery,8–10 and guarding pain is greatest immediately after plantar incision and gradually diminishes over several days.4,11 It is expected that an incision and acute tissue damage should generate the greatest SA immediately after injury, and the SA should gradually diminish over hours or days. What We Already Know about This Topic Mechanisms causing pain at rest after surgery are unknown What This Article Tells Us That Is New In rats, skin incision had little effect on guarding behavior, a measure of pain at rest, or spontaneous nociceptor activity Incision of skin and deeper tissue increased guarding behavior and spontaneous activity, suggesting that pain at rest after surgery reflects sensory nerve response to deep tissue injury However, in previous studies, SA was not evident in mechanosensitive afferents immediately after plantar incision,3 whereas significant SA was present 1 day after incision.12 We first suggested that nociceptors, which developed SA after incision, were mechanically insensitive afferents or chemosensitive afferents.13–15 These afferents are not easily identified by using a mechanical search stimulus in normal tissue before incision3 but can be sensitized and distinguished 1 day after tissue injury.12 However, when we applied an electrical stimulus to skin to recruit both mechanosensitive and mechanoinsensitive afferents, SA was still not evident immediately after plantar incision, indicating that mechanoinsensitive skin afferents were not the origin of SA. In this study, we hypothesized that incision of skin was not sufficient to cause persistent activation of nociceptors, but incision into deep tissue produced the majority of SA in nociceptors and guarding behavior after plantar incision. Our recent studies showed that skin incision induced modest SA in dorsal horn neurons (DHNs), whereas much greater SA was present after skin plus deep tissue incision.16,17 In addition, this high SA in DHNs after skin plus deep tissue incision could be inhibited by intraplantar bupivacaine injection, indicating a causal role of primary afferent input.16,17 We examined the entire time course of pain behaviors of rats with a sham incision procedure, skin incision, or skin plus deep tissue incision. SA and responses to mechanical and heat stimuli of nociceptors were recorded in vivo from separate groups of rats 1 day after sham procedure, skin incision, or skin plus deep tissue incision or 7 days after skin plus deep tissue incision. Pain behaviors were also measured on the same rats that underwent nerve recordings.