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Review
. 2017 Dec 1;67(6):469-482.

To Treat or Not to Treat: The Effects of Pain on Experimental Parameters

Norman C Peterson  1 , Elizabeth A Nunamaker  2 , Patricia V Turner  3
Affiliations
Review

To Treat or Not to Treat: The Effects of Pain on Experimental Parameters

Norman C Peterson et al. Comp Med. .

Abstract

A common dilemma faced by all animal bioethics committees arises when exceptions are proposed to the use of analgesics in painful procedures. The committee and researcher must weigh the possible confounding effects of including additional drugs (analgesics) in their treatment regimen against the moral obligation to perform humane research. Often neglected in these considerations are the potential confounding effects of unrelieved pain and consistency with pain-relieving practices in human medicine. In this review, we summarize what is currently known regarding the molecular and physiologic effects of pain and analgesics in common animal models used across several therapeutic areas. This work is intended to help provide guidance and assurance that a comprehensive approach has been taken when contemplating how pain relief will be applied in animal research protocols.

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Figures

Figure 1.
Figure 1.
Examples of key inflammatory cell types and mediators involved in neuroimmune activation and inflammation. Modified from references and .
Figure 2.
Figure 2.
Timeline of neuroimmune system activation and pain response following injury. The timeline is important to consider when evaluating the potential influence of administering analgesics, in particular, whether acute or chronic effects are being studied in a specific model. Modified from references and .
Figure 3.
Figure 3.
Pain is a stressor for the body that leads to emotional, physiologic, and behavioral responses. The physiologic response can lead to immunosuppression by stimulating glucocorticoid and catecholamine release. IL12 is a major inducer of Th1 responses, whereas IL10 antagonizes its effects and favors Th2 responses; both cytokines are predominately produced by activated monocytes. Catecholamines inhibit IL12 and stimulate IL10 production, whereas glucocorticoids inhibit IL12, but do not affect IL10 production. Thus, both glucocorticoids and catecholamines selectively suppress Th1 and favor Th2 responses, thereby suppressing cell-mediated immunity. Cortisol simultaneously 1) decreases the production of proinflammatory molecules (IL1, TNF, GM-CSF, IL2, IL3, IL4, IL5, IL8, prostaglandins, and leukotrienes); 2) reduces extravasation of inflammatory cells with inhibition of neutrophil function; and 3) induces apoptosis in lymphocytes and eosinophils.
Figure 4.
Figure 4.
Decision tree for petitions to withhold analgesics in painful procedures involving laboratory animals. To minimize the period during which pain and distress are experienced and regardless of the decision, the experiment should be designed so that the endpoints and objectives are reached as quickly as possible. *, Most studies have both mechanistic and translational components, and the relationship of these 2 objectives need to be considered in regard to alleviation of pain in the model.
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