Rats with weak conditioned pain modulation (CPM), a measure of endogenous analgesia, experience longer recovery times from mechanical hypersensitivity following surgery compared to rats with stronger CPM, according to a study published in the April issue of Anesthesiology. The research, which is consistent with observations in humans, was led by Christopher Peters, Wake Forest University, Winston-Salem, US, and provides a new method for investigating CPM and postsurgical pain in animals. It also points to one mechanism, noradrenergic signaling, that may be involved in the relationship between CPM and resolution of pain after surgery.
"This is an impressive example of back translation [from humans to animals] in pain research," wrote David Yarnitsky, Rambam Health Care Campus, Haifa, Israel, and Albert Dahan, Leiden University Medical Center, the Netherlands, in an accompanying editorial.
From people to rats
It was Yarnitsky's own clinical work that inspired the current research. Chronic pain following surgery is a major problem that affects at least 10 percent, and possibly as many as 50 percent, of patients who undergo common surgical operations (Kehlet et al., 2006). Suspecting that individual differences in endogenous analgesia may play a role in these adverse outcomes, Yarnitsky has found that patients with lower CPM—lower induction of diffuse analgesia throughout the body following an intense, focal pain stimulus—prior to surgery were more likely to have chronic pain six months after thoracotomy (surgical opening of the chest; Yarnitsky et al., 2008). Preoperative CPM also predicts pain following abdominal surgery (Wilder-Smith et al., 2010).
To further examine the relationship between CPM and postsurgical pain, and to look for mechanisms underlying this association, Peters and colleagues modeled the two phenomena in rats. Overall, the research is an "effort to try to make the studies that we're doing in rodents a little more translatable to humans," said Peters.
To study CPM, the researchers used a paradigm in which capsaicin administered to the forepaw increases hind paw withdrawal thresholds to mechanical stimuli. To model postsurgical pain, the researchers performed partial ligation of the L5 spinal nerve. Nerve injury is a proposed risk factor for developing chronic pain, explained Peters, so "we wanted a model that had a neuropathic component … and that we knew would spontaneously recover," he said. To examine the rats' recovery, the researchers measured mechanical withdrawal thresholds in both hind paws until 70 days post-surgery.