Respiration Features Reflect Stress and Inflammatory Pain Conditions in Mice Open Access

Jordano, James (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/1g05fc694?locale=en
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Abstract

Pain often occurs with physical trauma and disease. The associated pain experience can vary greatly between patients, including: the type of pain, an individual’s pain sensitivity, and the subjective perception of pain. This pain experience is often studied using rodent models though quantifying pain in rodents is difficult. Accepted pain measures have failed to show consistency from multiple studies across different pain types, stunting our understanding of pain and the development of solutions for the clinic. A new method of quantifying pain would contribute a clearer picture of pain experienced across different injury types and different analgesic effects; Respiratory features are such potential measures. Respiratory rate (RR) and respiratory rate variability (RRV) are physiological variables that can be recorded in a natural environment. RRV, for instance, has previously been related to pain responses in mice with chronic inflammatory pain and spinal cord injury. To further examine RR and RRV as pain measures, it is necessary to identify other variables that may affect it—including stress. While recording mice in home cages (asleep) and in restraint tubes (awake and anesthetized), RR and RRV were studied under noxious and non-noxious conditions. A well-characterized pain model—formalin injection—was used to produce a short and robust biphasic pain response. When formalin was administered to restrained mice, respiration rate (RR) was elevated in the formalin group (n=8) relative to the baseline group (n=8). Additionally, the anesthetized mice group’s (n=7) RRV was elevated after formalin injection relative to their baseline RRV—a pattern that was not present while the mice were awake and restrained. These results suggest both stress and pain affect respiratory patterns independently; RR seems to change when animals are awake and stressed, while RRV changes when animals are not awake and unstressed. Future studies of awake mice experiencing pain in non-stressful environments are necessary to illuminate the nuances of the intertwined relationship of stress and pain.

Table of Contents

I. INTRODUCTION…………………………………………………………………………………………………….…1

II. METHODS……………………………………………………………………………………………………….……….6

2.1 Ethics Statement……………………………………………………………………….……………………….6

2.2 Animals………………………………………………………………………….…………………………………..6

2.3 Experimental Summary—Restraint…………………………………………………………………….6

2.4 Restraint Tube Setup…..……………………………………………………………………………………..7

2.5 Accelerometer Setup………………………………………………………………………………………….9

2.6 Injections……………………………………………………………………………………………………………9

2.7 Experimental Summary—Home Cage Recordings..…………………………………………..10

2.8 Experimental Summary—Anesthesia Endpoint…..………………………………..………....11

2.9 Analysis and Statistics……………………………………………………………………………..……….12

III. RESULTS

3.1 Restraint Group Comparisons…………………………………………………………………………..14

3.2 Home Cage Comparisons………………………………………………………………………………….14

3.3 Anesthesia Endpoint………………………………………………………………………………………...14

3.4 Restraint—Event Duration….…………………………………………………………………………….16

3.5 Restraint—Heart Rate………………………………………………………………………………………17

IV. DISCUSSION…………………………………………………………………………………………………………...18

V. SOURCES CITED………………………………………………………………………………………………………21

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