ILAR Journal Online, Volume 40(3) 1999: Animal Models of Pain

Online Issues

<< All Back-issues

<< This Issue's Table of Contents

ILAR Journal V40(3) 1999
Animal Models of Pain

Introduction
G. F. Gebhart

Acute pain is a commonplace experience. A pin prick, a paper cut, or unexpectedly touching a heated surface produces pain of short duration and typically evokes a protective withdrawal reflex. Experiments in nonhuman animals have for the most part employed stimuli that produce acute pain of short duration and moderate intensity. Such studies have helped us understand much about basic mechanisms of pain processing, revealing the basic anatomy and chemistry of pain and pain control. Accordingly, these animal models of pain have become standards in the screening of putative analgesics. Ethically, these models are not generally problematic because animals are presented with short-duration, limited-intensity stimuli from which they can escape (that is, withdrawal reflexes are typically evoked).

Unfortunately, most human pain conditions, and particularly the most debilitating pain conditions, are not associated with limited-duration experimental stimuli but rather are associated with persistent pain that can wax and wane in intensity and be difficult to control. Pain is the defining characteristic in a wide range of conditions, including headache, low back pain, cancer, arthritis, and surgery. The American Pain Society (4700 W. Lake Avenue, Glenview, Illinois 60025-1485) estimates that 50 million Americans are partially or totally disabled by pain. With respect to headache and head pain alone, 150 million workdays are lost annually. Low back pain is also a common problem, and it is estimated that 22% of work-related injuries involve back pain and consequent lost productivity. Each of the nearly 25 million annual surgical procedures in the United States is invariably associated with postsurgical discomfort and pain. Pain is also associated with many cancers, and a common fear among cancer patients is that pain will develop and be uncontrollable. Every patient with cancer should have the reasonable expectation that pain will be controlled. In diagnostic and intermediate stages of cancer, however, 30 to 45 % of cancer patients experience moderate to severe pain. In advanced stages, nearly 75% of cancer patients have pain that is moderate, severe, or very severe. The distressing aspect of such statistics about pain in cancer and other persistent pain conditions is that many many individuals suffer significantly.

Although we have learned much about the anatomy, physiology, and neurochemistry of pain, the information presented above emphasizes the reality that not all pains are the same and, consequently, not all pains are controlled well with the treatment strategies currently available. Since the mid-1980s, investigators have strived to develop nonhuman animal models that closely replicate persistent pain conditions seen in humans. Tissue injury and inflammation are commonly associated with a variety of clinical conditions leading to persistent pain. Accordingly, new animal models to study these types of pain conditions differ in significant ways from earlier, acute pain models. Ethically, these new models present a challenge because they develop circumstances that most guidelines for the use of nonhuman animals in research identify as those to be avoided. How do you, as a laboratory animal veterinarian or a member of an institutional animal care and use committee (IACUC¹), evaluate protocols that involve such new models? How is potential benefit weighed against cost? This issue of ILAR Journal is devoted to discussing the ethical aspects of such work and to describing different models that have been developed to help understand what are acceptable and unacceptable approaches to the study of persistent pain.

Jerrold Tannenbaum (1999) in the lead article discusses several important principles related to pain research in animals and provides ethical guidelines for IACUCs. These guidelines are important to IACUCs and investigators alike and raise several challenging issues. Each subsequent article addresses important pain research models in nonhuman animals. Many models of persistent pain employ inflammogens, which produce discomfort and are associated with hyper-algesia (that is, an enhanced response to a noxious stimulus; sunburn is a typical example). Ren and Dubner (1999) discuss a number of such models associated with skin, subcutaneous tissue, and joint inflammation (somatic structures). Studies employing such models have led to significantly improved understanding of mechanisms of somatic pain, particularly mechanisms and modulation of hyperalgesia. There is now active development by the pharmaceutical industry of drug strategies for prevention and control of hyperalgesia and clinical evidence that such strategies work well. Visceral pain is distinct and different in many ways from pain that arises from skin, muscle, and joints. Ness (1999) discusses several models of visceral pain that have clarified and elaborated on the unusual nature of pain arising from the internal organs. Functional bowel disorders (such as irritable bowel syndrome and nonulcer dyspepsia) and interstitial cystitis are examples of persistent visceral pain that currently perplex physicians and patients alike. Finally, as indicated above, postsurgical pain is common yet not always well controlled. Brennan (1999) describes a relatively new and novel model for the study of postsurgical incisional pain. His studies have revealed that postsurgical pain differs significantly from inflammatory pain associated with skin or subcutaneous issues, and the model has helped clarify pain control strategies in the postsurgical patient.

Although pain accompanies a variety of procedures and is associated with many disease conditions, pain is no longer considered by the health care community as only a symptom. Long-lasting, chronic pain is in itself considered a disease or syndrome. The models described in this issue of ILAR Journal comprise a significant step in understanding the mechanisms by which pain can become persistent and eventually debilitating. It is the hope of ILAR that both the importance of such models and the obligations of investigators who use them are made clearer in this issue of the Journal.

¹ Abbreviation used in this article: IACUC, institutional animal care and use committee.

References

Brennan TJ. 1999. Postoperative models of nociception. ILAR J 40:129-136.

Ness TJ. 1999. Models of visceral nociception. ILAR J 40:119-128.

Ren K, Dubner R. 1999. Inflammatory models of pain and hyperalgesia. ILAR J 40:111-118.

Tannenbaum J. 1999. Ethics and pain research in animals. ILAR J 40:97-110.