A novel operant-based behavioral assay of mechanical allodynia in the orofacial region of rats

Abstract

Background Detecting behaviors related to orofacial pain in rodent models often relies on subjective investigator grades or methods that place the animal in a stressful environment. In this study, an operant-based behavioral assay is presented for the assessment of orofacial tactile sensitivity in the rat. New Methods In the testing chamber, rats are provided access to a sweetened condensed milk bottle; however, a 360° array of stainless steel wire loops impedes access. To receive the reward, an animal must engage the wires across the orofacial region. Contact with the bottle triggers a motor, requiring the animal to accept increasing pressure on the face during the test. To evaluate this approach, tolerated bottle distance was measured for 10 hairless Sprague-Dawley rats at baseline and 30 minutes after application of capsaicin cream (0.1%) to the face. The experiment was repeated to evaluate the ability of morphine to reverse this effect. Results The application of capsaicin cream reduced tolerated bottle distance measures relative to baseline (p<0.05). As long as morphine did not cause reduced participation due to sedation, subcutaneous morphine dosing reduced the effects of capsaicin (p<0.001). Comparison with Existing Method For behavioral tests, experimenters often make subjective decisions of an animal’s response. Operant methods can reduce these effects by measuring an animal’s selection in a reward-conflict decision. Herein, a method to measure orofacial sensitivity is presented using an operant system. Conclusions This operant device allows for consistent measurement of heightened tactile sensitivity in the orofacial regions of the rat.

Animal models of migraine and experimental techniques used to examine trigeminal sensory processing

“…Here, animals are trained to drink a reward while forced to place their face through temperature controlled thermal pads. Pain is assessed as a reduction in amount of reward consumed (quantified by number of licks) as well as contacts against the thermal pads [175, 176]. Recent work has shown that nitroglycerin treatment can decrease the amount of licks/contacts in wild type mice [177] indicating an increased sensitivity to thermal orofacial stimulation.…”

Core Outcome Measures in Preclinical Assessment of Candidate Analgesics

“…Figure 8 also shows that the capsaicin-induced hypersensitivity to 48°C thermal punishment can be alleviated by the transient receptor potential V1 antagonist (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (AMG9810) (30 mg/kg), but not by the κ opioid receptor agonist methyl 4-[2-(3,4-dichlorophenyl)acetyl]-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate (GR89696) (Neubert et al, 2007). This procedure has also been adapted for use in mice (Neubert et al, 2008; Ramirez et al, 2015) and for use with noxious mechanical rather than thermal stimuli (Rohrs et al, 2015).…”

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Development of a Mouse Pain Scale Using Sub-second Behavioral Mapping and Statistical Modeling

“…The current behavior assays to assess pain sensation in rodents can be broadly classified as operant pain assays, spontaneous pain detection assays, and reflexive withdrawal assays (Barrot, 2012; Le Bars et al, 2001; Mogil, 2009; Yuan et al, 2016). Operant assays typically involve animals’ successfully completing a task or learning to avoid or prefer a chamber that is associated with pro- or anti-nociceptive stimuli or experiences (Hung et al, 2015; Mauderli et al, 2000; Nag and Mokha, 2016; Rohrs et al, 2015). Because these assays require normal learning and memory processes for the animal to report its preference or avoidance, the failure of an animal to learn or remember a pro-nociceptive chamber or task may not necessarily indicate a lack of pain.…”