Pharmacological sensitivity of reflexive and nonreflexive outcomes as a correlate of the sensory and affective responses to visceral pain in mice

Abstract

Pain encompasses both sensory and affective dimensions which can be differentially modulated by drugs. Here, we compare the pharmacological sensitivity of the sensory and affective responses using acetic acid-induced abdominal writhings (sensory-reflexive outcome) and acetic acid-induced depression of reward seeking behaviour (RSB, affective-nonreflexive outcome) to a highly palatable food in mice. We found that the expression of RSB critically depends on factors such as sex and previous knowledge and type of the food stimulus. Intraperitoneal administration of acetic acid (iAA) produced a long-lasting (beyond the resolution of writhing behaviour) and concentration-dependent decrease on both appetitive-approach and consummatory dimensions of RSB. Ibuprofen and diclofenac were much more potent in reversing AA-induced changes in RSB: latency to eat (ED ₅₀ = 2 and 0.005 mg/kg, intraperinoneally, respectively) and amount consumed (ED ₅₀ = 11 and 0.1 mg/kg) than in AA-induced writhing (ED ₅₀ = 123 and 60 mg/kg). Morphine and duloxetine inhibited the writhing response (ED ₅₀ = 0.8 and 6 mg/kg, respectively) but not the AA-induced changes in RSB. Caffeine was ineffective in both AA-induced writhing and RSB changes. Overall, this study characterized a preclinical mouse model of hedonic deficits induced by pain that can be used to assess affective responses as well as complementary classic reflexive approaches in the evaluation of candidate analgesics.