Abstract
Background: Our objective was to establish a novel, unbiased metric of inflammatory, orofacial pain. Method: Rats were placed individually into cages equipped with running wheels, and allowed an acclimation period of 17 days. Diurnal and nocturnal voluntary running behaviors were recorded. After day 17, rats were deeply anesthetized and divided into mustard oil, vehicle (mineral oil) and drug (ibuprofen) groups. Injections of mustard oil or mineral oil were made into the vestibule superior to the maxillary molar. Running wheel behavior was recorded for three days following the procedure. Results: After acclimation, the average percentage of running behavior that occurred at night was 94% +/-1% SE. Mustard oil injections caused externally observable, unilateral inflammation. On average, mustard oil injections significantly reduced nocturnal running on the first and second nocturnal periods post-injection. The non-steroidal anti-inflammatory, ibuprofen, significantly improved running behavior during the second nocturnal period, which was abolished when removed during the third nocturnal period. Conclusions: We conclude that unilateral injections of algogens in the vestibule coupled with analysis of nocturnal running behavior is an effective method to measure acute inflammatory pain for three days that mirrors many painful clinical situations. The model could be used as inexpensive, quantitative method to evaluate putative pain relieving therapeutics.
Highlights
The United States is currently facing an epidemic of prescription painkiller abuse
The objective of our study was to assess the role of orofacial nociception and inflammation on voluntary running behavior in rats
Running wheel activity was greatest during the nocturnal period (Fig. 1)
Summary
The United States is currently facing an epidemic of prescription painkiller abuse. Addictions and overdoses to prescription opioids are steadily on the rise, as highlighted by a recent report from the CDC indicating that overdose deaths from prescription opioids exceed deaths from cocaine and heroin combined. The United States spends approximately, $500 billion annually in costs associated with treating painful conditions [1]. There is a growing impetus and need for novel, non-addicting therapies to treat pain. There are many barriers to developing new therapies, which include appropriate pre-clinical animal testing. There has been considerable debate on the most appropriate pre-clinical animal model used to approximate human conditions. Many pre-clinical animal models utilize pain-stimulating (evoked) behaviors [2 - 5], where a variety of measures such as withdrawal latencies, threshold, and number of evoked responses are measured. Differentiating between evoked pain and spontaneous pain is not straightforward [7] and it has been suggested that ongoing inflammatory pain should not be characterized as spontaneous pain [7]. Our objective was to establish a novel, unbiased metric of inflammatory, orofacial pain
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