Background & Aims

An estimated 22% of people are living with chronic pain1, which causes significant disability and diminished quality of life and is poorly managed by existing treatments. Among individuals who are prescribed long-term opioids for the management of chronic pain, 21-29% report opioid misuse behaviours and 8-12% of chronic pain patients with long-term opioid prescription develop Opioid Use Disorder (OUD)2. As a result, it is essential to develop evidence-based regimens that reduce the risks associated with long-term opioid prescription for the management of chronic pain, including tapering (incremental decrease) of the dose of opioids. This project aims to develop a novel preclinical paradigm to investigate opioid tapering through the use of the spared nerve injury (SNI) model of chronic neuropathic pain in the mouse.

Methods

We will use the SNI model of neuropathic pain on CD-1 mice, and then subject mice to a 1:1 fixed ratio (FR) (FR1; 1 response yields 1 35 ?l reward dose with a reward-paired cue light) oral self-administration of morphine in an operant chamber to induce opioid addiction. Mice will be divided into one of four groups (equal numbers of male and female mice): tapering/cold turkey withdrawal, sham/SNI surgery. Over a two-week acquisition period all groups will have daily 1-hour access to a 0.5 mg/ml morphine solution in sweetened condensed milk. Next, the average amount of morphine consumed will be gradually reduced each day via intraperitoneal injection for the tapering group until mice no longer receive morphine, while the cold turkey group will experience sudden withdrawal from the end of the acquisition period until the reacquisition period. To operationalize relapse behaviours, we will examine reacquisition behaviours of mice given access to the initial FR1 schedule following cessation.

Results

Preliminary data suggests that opioid tapering paradigms are more effective than cold turkey withdrawal in reducing the incidence of relapse-like behaviours as is found in clinical applications. Our preliminary findings also suggest that CD-1 mice display sex-dependent differences in oral self-administration of morphine during the acquisition period that reflect clinical observations.

Conclusions

Future experiments will investigate whether there are opioid tapering paradigms that reduce withdrawal symptoms in distinct sub-populations, with particular attention to sex-specific or incentive salience-specific outcomes.

References

Schopflocher, D., Taenzer, P., & Jovey, R. (2011). The prevalence of chronic pain in Canada. Pain research & management, 16(6), 445–450. https://doi.org/10.1155/2011/876306

Vowles, K. E., McEntee, M. L., Julnes, P. S., Frohe, T., Ney, J. P., & van der Goes, D. N. (2015). Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain, 156(4), 569–576. https://doi.org/10.1097/01.j.pain.0000460357.01998.f1

Back, S. E., Payne, R. L., Wahlquist, A. H., Carter, R. E., Stroud, Z., Haynes, L., Hillhouse, M., Brady, K. T., & Ling, W. (2011). Comparative profiles of men and women with opioid dependence: results from a national multisite effectiveness trial. The American journal of drug and alcohol abuse, 37(5), 313–323. https://doi.org/10.3109/00952990.2011.596982

Presenting Author

Hannah Derue

Poster Authors

Hannah Derue

BSc(Hons)

McGill University

Lead Author

Alicia Zumbusch

McGill University

Lead Author

Jeffrey Mogil

McGill University

Lead Author

Alfredo Ribeiro da Silva

McGill University

Lead Author

Topics

  • Models: Chronic Pain - Neuropathic