Descending Control of Nociception Poorly Predicts the Development of Persistent Postsurgical Pain-like Behavior in Consomic Dahl S Rat Strains

Abstract

Background Chronic postsurgical pain (CPSP) is a poorly recognized outcome of surgery where patients experience pain long after healing from the surgical insult. Descending Control of Nociception (DCN), a phenomenon whereby application of a strong nociceptive stimulus to one part of the body of animals inhibits pain in remote body regions, offers one strategy to identify a propensity to develop CPSP-like behavior. Here we used a consomic rat panel to test the hypothesis that pain persistence is mechanistically linked to ineffective DCN. Methods Male and female Brown Norway (BN), Dahl S (SS) and 8 consomic strains (SS-xBN) were used to determine the presence of CPSP-like behaviors by using paw-withdrawal threshold evaluation (von Frey method) in the area adjacent to a hind paw plantar incision. DCN was assessed by measuring hind paw-withdrawal thresholds (Randall-Selitto method) after capsaicin (125µg) injection into a forepaw. Consomic rats were developed by introgressing individual BN chromosomes on the SS rat genetic background, as SS rats lack preoperative DCN. Results Substitution of several chromosomes from the “pain-resistant” BN to the “pain-prone” SS/MCW reduced mechanical nociceptive sensitivity and increased endogenous pain modulation capacity by differing degrees. Statistical modeling of these data revealed that DCN is a poor general predictor of the propensity to develop CPSP-like behavior (poor fit for Model 1). However, a significant strain-by-DCN interaction was revealed (Model 3, -2*log likelihood; 550.668, -2ll change; 18.093, p = 0.034) with SS-13BN and SS-15BN strains showing a negative DCN relationship with CPSP-like behavior. Conclusions DCN poorly predicted which rat strains developed CPSP-like behavior despite controlling for genetic, environmental and sex differences. Two consomic strains that mimic clinical chronic postsurgical pain criteria and display a strong negative correlation with DCN were identified, offering novel candidates for future experiments exploring mechanisms that lead to chronic postsurgical pain.