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 (ED50 = 2 and 0.005 mg/kg, intraperinoneally, respectively) and amount consumed (ED50 = 11 and 0.1 mg/kg) than in AA-induced writhing (ED50 = 123 and 60 mg/kg). Morphine and duloxetine inhibited the writhing response (ED50 = 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.

Comprehensive Preclinical Assessment of Sensory, Functional, Motivational-Affective, and Neurochemical Outcomes in Neuropathic Pain: The Case of the Sigma-1 Receptor

“…Discrimination between appetitive and consummatory behaviors in the context of pain-depressed behaviors can also reveal distinct neurobiological underpinnings and pharmacological sensitivity. 25,60 Most studies use sham-operated mice as controls. Indeed, sham operation was undistinguishable from naıve condition as it regards to sensitivity to mechanical von Frey stimulation.…”

“…Reward-Seeking Behavior (RSB) Based on the Approach and Consumption of White Chocolate. The changes in the reward-seeking behavior task when mice were offered palatable food, as previously described, 25 were used to evaluate the affective consequences of neuropathic pain. The task is based on the approach and consumption of white chocolate, which allowed analyzing the appetitive and consummatory aspects of motivational behavior.…”

“…23,24 Recently, our group has presented data using white chocolate as a highly palatable food in which an increase in the latency of approach and decreased consumption after visceral nociceptive stimulation were observed; making the study of this type of motivated responses feasible in chronic pain models. 25 In addition, the recent development of computer analysis has been used to study changes in gait produced by the presence of pain or other manipulations. The possible alterations produced by pain in the gait represent a functional indicator whose recovery is valuable to support a molecular target or a drug.…”

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

“…AA induces a writhing response when it is intraperitoneally administered (26,27). It has been reported that the agent may cause the indirect release of noxious substances including bradykinins, serotonin, histamine and PGs (28)(29)(30).…”

The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?

“…Finally, we also tracked research reports that used some of the most recent surrogate pain measures in rodents to investigate different aspects of the pain phenotype, such as interference in physical functioning (postural changes and grip strength deficits), pain-depressed behaviors (exploratory locomotion, home cage activity, borrowing and nesting behaviors, intracranial self-stimulation, and wheel running), and facial expressions in pain conditions. Readers should note here that in addition to these behavioral measures, there are others which are not reviewed here, including (but not limited to) conditioned place aversion and preference induced by pain and analgesia, and specific tests to evaluate depression-like behaviors in rodents; these measures can also yield useful data regarding the rodent pain phenotype (Cobos and Portillo-Salido, 2013;Navratilova et al, 2013;Yalcin et al, 2014;de la Puente et al, 2017). With the measures covered in the present review we aim to provide a sense of how preclinical pain assessment has evolved from earlier decades to the present time.…”