Ethics and Pain Research in Animals Jerrold Tannenbaum ...

Ethics and Pain Research in Animals

Jerrold Tannenbaum

Introduction

Pain research in animals raises distinctive and some-times difficult ethical issues for institutional animalcare and use committees (IACUCs1), attending veteri-

narians, and investigators. In this paper, I explore and defenda number of widely accepted ethical principles regardinganimal pain. I develop from these principles guidelines foruse by IACUCs in assessing the humaneness of pain researchin animals. Relevant ethical standards in current US laws andregulations and in policy statements of professional researchassociations are also examined.

Ethics and Animal Research

Attention to ethics is an essential part of the work of IACUCs,veterinarians, animal researchers, and all who affect the livesof research animals. The entire enterprise of animal researchis motivated by an ethical principle—the belief that it is notonly appropriate but morally obligatory to try to understand,alleviate, and prevent conditions that harm and kill so many.It would be incongruous and inconsistent to engage in animalresearch for this ethical reason and deny the importance ofdealing ethically with the animals essential to this research.Moreover, virtually everyone accepts the principle that wehave a fundamental ethical obligation to treat properly ani-mals we use for our own benefit. Many scientists and veteri-narians believe that it is a privilege to use animals in research(Dubner 1983). Regarding animal use as a privilege involvestreating research animals with appreciation, gratitude,respect, and a genuine concern for their needs and welfare.

Jerrold Tannenbaum, J.D., was in the Department of Environmental andPopulation Health, Tufts University School of Veterinary Medicine, NorthGrafton, Massachusetts, when he wrote this article. He is currently a Profes-sor in the Department of Population Health and Reproduction, School ofVeterinary Medicine, University of California-Davis, Davis, California.

'Abbreviations used in this article: AWA, Animal Welfare Act; Guide,Guide for the Care and Use of Laboratory Animals; IACUC, institutionalanimal care and use committee; IASP, International Association for theStudy of Pain; PHS, Public Health Service; US Principles, US GovernmentPrinciples for the Utilization and Care of Vertebrate Animals Used in Test-ing Research and Training.

Legal Recognition of the Importance ofEthics in Animal Research

Congress and agencies that regulate animal research haverecognized the importance of ethics by articulating a numberof ethical rules IACUCs and others involved in animal re-search are expected to follow. The Preamble to the federalAnimal Welfare Act (AWA1) declares that the entire statuteand its regulatory structure are intended "to insure that ani-mals intended for use in research facilities or for exhibitionpurposes or for use as pets are provided humane care andtreatment" (7 USC 2131(1)). The terms "humane care andtreatment" and treating animals "humanely" are used by mostpeople, and clearly by the AWA, as synonyms for ethicalcare and treatment and treating animals as we are ethicallyobligated to do (Tannenbaum 1995, p 120-121, 419-420).The statute and its regulations contain many ethical obliga-tions made legally enforceable, such as the requirements thatprocedures "will avoid or minimize discomfort, distress, andpain to the animals" (9 CRR 2.31(d)(l)(i)) and that "animals'living conditions will be appropriate for their species andcontribute to their health and comfort" (2.31(d)(l)(vi)).

Public Health Service (PHS1) policies also contain ethicalstandards, many of which are set forth in the US GovernmentPrinciples for the Utilization and Care of Vertebrate AnimalsUsed in Testing, Research, and Training (PHS 1996). Forexample, "procedures involving animals should be designedand performed with due consideration of the relevance tohuman or animal health, the advancement of knowledge, orthe good of society" (PHS 1996, p i). This principle requiresthat what is done to animals in research be justified by prac-tical or theoretical results. The first sentence of the Guide forthe Care and Use of Laboratory Animals (Guide]), whichinstitutions covered by PHS rules must consult, proclaims anethical principle intended to underlie the Guide's recommen-dations: "all who care for or use animals in research, teaching,or testing must assume responsibility for their well-being"(NRC 1996, p 1).

Attention to the ethical treatment of animals in researchis not just morally obligatory. It is required by law.

Pain in Animals: General Ethical Principles

In discussing ethical considerations relating to pain researchin animals, it is important to begin with general ethical prin-ciples. An essential part of ethical deliberation involves

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giving reasons for ethical beliefs, which involves appealingto underlying principles. If the soundness of these principlescan be maintained independently of particular applications,the principles can then be applied confidently to these appli-cations. In the area of pain research, there is a special reasonto begin with general ethical principles. Although laws andregulations contain ethical rules for IACUCs and investiga-tors regarding animal pain, these rules do not specificallyaddress the intentional causation of pain that is characteristicof much pain research in animals. The rules instead invokegeneral and widely held ethical standards relating to animalpain. Application of these governmental ethical rules to painresearch in animals requires an understanding of the under-lying ethical standards that give these rules meaning andspecificity.

Centrality of Animal Pain inOur Ethical Framework

there still exist among some scientists remnants of behavior-ist notions that animals do not feel pain, or that feelings ofpain in animals are of no practical significance because theyare incapable of expression in the language of chemistry orphysics (Rollin 1987, 1997). Many IACUC members haveencountered investigators who, when asked whether theirwork might cause animals pain, respond that one cannot re-ally know what animals feel or be certain that they feel painat all. They might look scruffy, depressed, or agitated, it issometimes said, but who can know what they feel if they feelanything? Such statements recognize the ethical relevance ofcausing pain but attempt to lessen or negate ethical issues byquestioning the reality of animal pain. Although doubts aboutanimal pain are less likely among pain researchers who useanimal models for human pain than among investigatorswhose work may secondarily cause animals pain, question-ing whether animals feel pain, or feel pain "as we do," can bea tempting neutralizer of unsettling ethical aggravations.

People apply many different ethical principles to their inter-actions with animals. One significant recent development inanimal ethics is growing acceptance by the public and mem-bers of the biomedical research community of the view thatanimals used in research should be provided enriched envi-ronments and positive psychological experiences (Rollin1995, p 3-26). However, this view is recent and is not yetuniversally extended to all species. For at least the past 100yr, most people in Western societies have believed their pri-mary ethical obligation to all animals is not to cause themunnecessary or unjustifiable pain (Tannenbaum 1995, p 120-122). Most laws relating to animal use (such as cruelty-to-animals statutes, humane slaughter laws, and most laws andregulations governing animal research) require that animalsused for legitimate purposes not be caused pain if possibleand not be caused unnecessary pain if some pain is unavoid-able. The view that the capacity of animals to feel pain is theprimary source of our ethical obligations to them was arguedby the 18th century English philosopher Jeremy Bentham,who maintained that the important question regarding ani-mals is not "Can they reason! nor Can they talk! but Canthey sufferT (1948, p 311, emphases in original). Benthamalso argued that there is no ethical issue whatsoever if ananimal raised or used in research does not feel pain, distress,or discomfort. This position is accepted widely (but by nomeans universally) by the general public and biomedical sci-entists today.

Reality of Animal Pain

The principle that our primary obligation to animals is not tocause them unjustifiable pain presupposes that animals canexperience pain. It may seem obvious that animals feel pain.Moreover, using animals in pain research as a model forhuman pain clearly presupposes that animals feel pain; ifthey did not, the model would be pointless. Nevertheless,

Pain As a Fundamental Evil

Pain is not only an evil—something that is bad or a harm—but is an evil in itself. Pain is an evil simply because of theway pain feels and not for some other reason (although paincan have additional bad effects and for these reasons be evil).Pain is sometimes beneficial in signaling the presence ofsome problem such as injury or disease. However, the expe-rience of pain is bad in and of itself, which is why humansand animals generally avoid it. We do not ask why pain isbad, not just because we know that it is bad but because wecannot say anything more about it than that it is pain. Ifsomeone asked you to explain why feeling pain is a badthing, and if you took the question seriously, you wouldrespond that it is bad because it feels the way it does—thatpain is bad because it is pain. In other words, it is self-evident that pain is evil in and of itself.

Equality Principle

Several important ethical principles follow from the fact thatpain is an evil in itself. What I call the "Equality Principle"holds that a given amount or duration or severity of pain isequally an evil for any being—human or animal—experi-encing it. As philosopher Joel Feinberg explains,

If the essential character of pain and suffering themselvesmake them evil—evil not for their consequences but intheir intrinsic natures—then it follows that given magni-tudes of pain and suffering are equally evil in themselveswhenever and wherever they occur. An intense toothacheis an evil in a young person or an old person, a man or awoman, a Caucasian or a Negro, a human being or a lion. Askeptic might deny that a toothache hurts a lion as much asit does a human being, but once one concedes that lion painand human pain are equally pain—in the same sense andthe same degree—then one cannot deny that they are

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equally evils in themselves. All this follows necessarilyfrom the view that pain as such is an intrinsic evil, and notevil only because it tends to produce bad effects of otherkinds (Feinberg 1980, p 194).

If animals of a "lower" species experience less pain thanthose of a "higher" species under certain circumstances, thisfact could be relevant to determining whether a pain researchexperiment is justified on them, because it causes them insig-nificant pain, or is better done on them than on animals of aspecies that would experience more pain. However, one can-not regard an experience of pain as less a harm or evil, andtherefore raising a less serious ethical issue, because thatexperience would occur in rats, for example, rather than incats or primates.

Justification Principle

The nature of pain as a fundamental evil also implies what Icall the "Justification Principle": Because pain is an evil,anyone who causes pain in a being that can experience itmust show that it is necessary and justifiable to cause thispain. Feinberg observes that we

. . . condemn and conscientiously avoid inflicting unneces-sary pain and suffering on other human beings simply be-cause we regard pain and suffering as an intrinsic evil. Thatis, we judge pain and suffering to be evil simply becausethey are pain and suffering. In the case of human beings, atleast, we never ask for any further reason that a given con-dition is evil and therefore to be avoided or corrected afterwe learn that it is a painful condition. The question "What'swrong with pain anyway?" is never allowed to arise(Feinberg 1980, p 194, emphases in original).

It is a basic ethical wrong—perhaps the most basic ethicalwrong of all—to harm another being without justification.Because pain is an evil, we act wrongly if we cause anyanimal we use for our own benefit or for the benefit of otheranimals unnecessary or unjustifiable pain. It is difficult tostate generally how strong a justification must be given forthe infliction of pain. It can, however, be said that causingany pain is not a trivial matter and requires not trivial butsubstantial justification.

Value Principle

From the Justification Principle and the fact that pain is anevil to animals follows a critically important ethical principlethat is often invoked by IACUCs when they consider researchlikely to cause animals pain. Because pain is an evil, more ormore severe pain is a greater evil than less or less severepain. Therefore, the more pain an experiment will cause ani-mals, the greater must be the justification. Expressed anotherway by what I call the "Value Principle," the more pain anexperiment or test will cause, the greater must be its value.

Saying that the value of an experiment must justify the levelor kind of pain the experiment causes is of course just tobegin ethical deliberation. People disagree about whethercertain kinds of animal uses are sufficiently valuable to jus-tify a certain level of animal pain. Some people, for example,believe that testing cosmetics is of sufficient value to justifyanimal pain; others disagree. Some people believe that ani-mal pain can never be justified by basic research that doesnot promise practical benefits for people or other animals;others disagree. It is possible to argue not only about whethersuch goals are sufficiently valuable to justify a certain levelof animal pain, but also about the relative ranking of thesegoals. Thus, one can maintain that although basic knowledgemay be valuable, it is not as valuable as practical knowledgein the sense that it justifies causing animals pain and cannotjustify as much animal pain as would applied medicalresearch.

There are other difficult issues in assessing and compar-ing the value of medical research relative to justification ofanimal pain (Tannenbaum 1995, p 485-486). For example,although research that could bring relief from suffering tomany people may often seem of greater value than researchthat would benefit only a few, if those few suffer grievouslyand lack means of relief, the urgency and value of research tohelp them may be greater. However we decide to character-ize the value of research, because pain is an evil to animalsand because more pain is a greater evil to them than less pain,the value of research causing that pain must be greater whenthe pain for the animals is worse.

Components of Value in Research

There are two components of the kind of value that is neededto justify animal pain caused by research: the value of theaims of the research and the level of its scientific soundness.Research that causes animals pain to test a new and poten-tially more effective pain-killing drug for cancer patientswill likely have an aim that is sufficiently valuable to justifythe infliction of some animal pain. A project that would causeanimals pain simply to amuse a "researcher" who enjoyswatching animals suffer has no value and would not justifythe infliction of any pain. However, good aims are not enoughfor the value that is required to justify animal pain. Ethicallyacceptable research must also have some level of scientificsoundness (sometimes termed "scientific merit"). Althoughthe results of research are often unpredictable, research thatwill cause animals pain must be based on accurate scientificknowledge, involve scientifically defensible hypotheses, anduse scientifically appropriate techniques. An investigatorwho wants to find better ways of alleviating pain in cancerpatients (a valuable aim) is no more justified causing pain toanimals than one who has a foolish aim if the proposedresearch of the former investigator is scientifically inept. Theinfliction of pain on the animals will still be pointless, andunjustified. Performing scientific experiments that are suffi-ciently valuable to justify animal pain includes being compe-


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tent to do the scientific work. Bad science cannot be goodethics, certainly when it involves causing animals pain.

Minimization Principle

From the Justification Principle follows the ethical principlethat is employed most frequently in current laws and regula-tions governing animal research. What I call the "Minimiza-tion Principle" holds that we should minimize pain experi-enced by research animals. Assuming one is justified in doingharm, doing less harm to a being is always better than doingmore harm. Less pain is less a harm or evil than greater pain.Therefore, one can never justify causing more pain to ananimal than one needs to cause. The Minimization Principleis best considered after the Value Principle because whethera certain amount or kind of pain is deemed necessary andtherefore justified will depend on whether the infliction ofany pain on an animal is justified by proposed research. Oncecausing some pain is justified, the Minimization Principlerequires that it be minimized, but this minimized level oramount of pain must also be justified by the value of theresearch. The Minimization Principle requires that no painbe caused if this is possible under the circumstances becauseno pain is the ultimate minimization of pain.

Conceptual Problems of Minimization

Although the Minimization Principle is persuasive, it willsometimes be difficult or impossible to apply it confidentlyto pain research in animals. This difficulty stems from thefact that experiences of pain have a number of different pos-sible components, including duration and severity, and avariety of different characteristics, such as sharp, dull, pierc-ing, throbbing, and burning. Given a specified severity andkind of pain (such as intense and sharp pain), we can say withconfidence that such pain experienced for 1 min is less thansuch pain experienced for 10 min. Given a specified durationof pain, the Minimization Principle requires causing thisduration of dull pain rather than sharp and burning pain,because we characterize the former as less pain. The principleis difficult to apply, however, when we compare differentdurations with different intensities and kinds of pain. Forexample, is 1 min of sharp and intense pain "less" pain than10 min of dull pain? Is dull pain more or less pain thanthrobbing pain? Does it become more after a certain intensityor time? When we add to the mix different numbers of ani-mals, the task of comparing and minimizing can becomeeven more difficult. For example, how many cats experienc-ing sharp and burning pain for 10 min will constitute morepain than 50 cats experiencing dull pain for several hours?When we attempt to make such comparisons across species(to determine, for example, whether pain would be mini-mized by doing an experiment on rats rather than cats), the

problems are magnified further because it may not be clearhow to compare pain felt by different species even when weknow that they feel pain.

Application of the Minimization Principle presupposesthat we can determine whether a given use of animals in-volves more or less pain than another. However, we cannotalways clearly say that some animals experience more painthan others because it is not clear that the term "pain" (evenwhen properly applied) always refers to the same entity ofwhich the relative amounts can be compared and then"lessened" or "minimized." It is not clear what it means tosay that 10 min of dull pain is the same amount of pain or ismore or less than 1 min of excruciating pain, except that wethink it is better—or more accurately, less bad—to experi-ence the former duration and type. It is not clear that the 1min of excruciating pain and the 10 min of dull pain are thesame thing or can be converted into amounts of the samething and compared for quantity.

When it seems difficult to determine whether one ap-proach minimizes pain because it is difficult to compare theamount of one kind of pain experience with another kind, wemust fall back on intuitive judgments and reliable behavioralevidence regarding what appears better or worse for ananimal or human to experience. Because the underlyingmotivation of the Minimization Principle is to assure thatanimals feel no worse than necessary, this approach seemsreasonable.

Fairness to Individual Animals

The Minimization Principle must be qualified by anotherimportant ethical principle. Talk of pain "minimization" maylead some people to think that the real ethical concern is thetotal amount of pain experienced and that our moral obliga-tion is to minimize this total. The following example illus-trates why this view is incorrect. Suppose a pain experimentcould achieve satisfactory results either by causing excruci-ating pain in five animals for 1 hr or moderate and well-tolerated pain in 20 animals for 1 day. It might be correct insuch circumstances to say that more total pain would becaused by using the 20 animals. However, I would argue thatusing the 20 animals would be ethically preferable, becauseeach individual animal will be harmed less. The ethical prob-lem in causing animals pain arises not from causing totalamounts of pain but from causing individual animals pain.There is no such thing as a totality of pain that exists in theworld. Individuals feel pain, and what makes pain evil is thatit is an evil to the individual experiencing it. Therefore, indetermining whether the infliction of animal pain is justified,we must ask whether what we are doing is fair to the indi-vidual animals we use. Sometimes considerations of fairnessto these individuals will mean that we demand too much ofeach animal by subjecting it to a great amount of pain if wecan accomplish the same end by having each animal usedsuffer less.

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The important ethical principle of fairness to individualsis embodied in the provision of the AWA regulations that"no animal will be used in more than one major operativeprocedure from which it is allowed to recover" (9 CFR2.31(d)(l)(x)) in the absence of scientific justification. Thisprohibition recognizes that although the total amount of painor distress, and indeed the total number of animals, may belessened if fewer animals are subjected repeatedly to majorprocedures, it can be unfair to each individual animal used todo this. In pain as in other kinds of research, fairness toindividual animals may sometimes require using more ratherthan fewer animals, extending rather than shortening theduration of an experiment, and not minimizing total pain anddistress.

Associated Negative Feelings

In considering ethical responsibilities relating to causinganimals pain, it is important to take into account unpleasantmental states that typically accompany pain. Some of thesestates (such as distress) may occur so frequently with feel-ings of pain that they may sometimes properly be describedas part of the pain experience itself. Others (like discomfort,fear, or anxiety) may sometimes be easier to separate phe-nomenologically from pain or be better viewed as reactionsto pain. What is ethically important about pain—what makesit an evil to animals as well as to humans—is that it feels bad.Other unpleasant feelings such as distress or discomfort alsofeel bad, and the same ethical principles apply to causingthem in animals as apply to causing pain. Therefore, in deter-mining whether causing animal pain in an experiment is ethi-cally justifiable, we must include in our deliberations otherunpleasant or negative animal experiences. The presence ofsuch feelings is likely to increase the total evil an animal willbe caused and thus increase the required minimum level ofjustification and value of a proposed experiment. The Mini-mization Principle requires pain researchers to minimizethese associated negative feelings (while still causing neces-sary pain) if minimization of such associated feelings ispossible given justified experimental aims.

The need to include negative feelings associated withpain in ethical assessment of pain research causes no smallconceptual, scientific, and practical problems. If there isdisagreement among philosophers and scientists about themeaning of the term "pain" in animals and lack of knowl-edge about its nature and causes, there is even greater dis-agreement about the meaning and causes of psychologicalstates in animals such as distress, discomfort, fear, or anxiety(Tannenbaum 1995, p 416-418). Nevertheless, such disagree-ments and lack of knowledge do not diminish the strength ofthe ethical principle that bad or unpleasant feelings inflictedon animals must be justified and minimized. Indeed this ethi-cal principle requires us to learn as much as possible aboutnegative mental states associated with pain so that they toocan be minimized in research.

Imprecision in Ethical DeliberationRelating to Animal Pain

Aristotle warned that different kinds of investigations requiredifferent levels or degrees of precision and that ethical dis-cussions are unreliable if they seek more precision than thesubject allows (Aristotle 1952, Book I, p 339). The ethicalprinciples relating to pain discussed above are widely ac-cepted and seem eminently reasonable. Their acceptance,however, does not mean that they can always be appliedprecisely. For example, sometimes knowing how to mini-mize pain is easy: If an animal is fully anesthetized, its painis minimized during the time of anesthesia. But when ani-mals feel pain—a situation common in pain research—it isoften impossible to know whether they are being causedabsolutely the minimum amount of pain necessary even whencomparisons of amounts of pain seem possible. There is stillmuch to be discovered about what behavioral and physi-ological signs indicate the presence of pain in various species.Pain behavior (and presumably pain perception) varies sig-nificantly among different individuals within species (Soma1987). Much remains to be learned about what kinds ofchemical and environmental interventions can lessen animalpain. However, the most serious problem for precisely esti-mating and then minimizing animal pain results from the factthat animals cannot talk about their pain. Adult humans canusually describe precisely when pain begins and ends, whereit is located, and how it feels. We estimate the severity ofhuman pain in terms of more intense versus less intense,sharp versus dull, piercing versus diffuse, throbbing versussteady, and with many other kinds of descriptions. All suchinformation can be critical to determining whether pain isbeing lessened or minimized. Perhaps many of these dis-criminations will some day be applied to animals based onsimilarities between their physiological states or behaviorand those of humans when we make these discriminations. Inlight of the inherent inability of animals to describe theirpain, it seems unlikely that we will ever be able to make suchdeterminations with anything approaching the precision wemake them regarding pain in humans.

Ethical consideration of animal pain in pain research,like the research itself, must often settle for imprecise orgross estimates of how much and what kind of pain andassociated negative feelings animals experience. It is there-fore more accurate to say that one's ethical obligation regard-ing animal pain is not to minimize it but to try to minimize itin light of best knowledge and practice. Moreover, becausepain is a fundamental evil to animals as it is to humans, thefollowing ethical principle seems appropriate: If there isreasonable scientific question about whether animals undercertain circumstances are or are not feeling pain or are feelingmore or less pain, we should err on the side of judging thatthey feel this pain or that they are feeling the worst or largestamount of reasonably attributable pain. By assuming thepresence of such pain and requiring sufficient justificationfor it, we may be able to assure that the research is ethicallyjustified whether or not it actually results in this pain.


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Animal Pain Research:Ethical Dilemma and Paradox

The general ethical principles discussed above help explainwhy pain research in animals can be so ethically trouble-some. Because pain is a fundamental evil, understanding andalleviating pain is among the most important tasks of bio-medical science. Estimates of the psychological and eco-nomic costs of pain are staggering. Data from the USNational Center for Health Statistics and other sources revealthat

. . . in 1988 112 million Americans (45 percent) experi-enced acute pain requiring medical care caused by 40 mil-lion injuries, 2 million burns, 5 million dental disorders, 10million nontraumatic musculoskeletal diseases, 3 millionchildbirths, 15 million with acute pain in the postoperativeperiod, and 37 million cases of visceral disease. Amongthis group 59 million, or 25 percent of the total population,experienced pain that was moderate to severe or excruciat-ing and required major therapy in the form of opioids andother therapeutic modalities (Bonica 1992, p 2).

An additional study estimated that in the same year,approximately 65 million Americans suffered chronic painfrom back disorders, arthritis, cancer, heart disease, and otherdisorders. Of this group, 48 million (19% of the total popula-tion) were partially disabled at least for weeks or months,and chronic painful conditions among Americans resulted inmore than 5 billion days of limited or bed disability and morethan 900 million lost workdays (Bonica 1992, p 2). A 1998National Institutes of Health Program Announcement forpain research states that

... pain is the most common reason individuals seek medi-cal care, with millions of medical visits annually; costingthe American public more than $100 billion each year inhealth care, compensation and litigation. . . . Pain-relateddisability presents a significant and costly liability toworkers, employers and society. In the workplace, a sig-nificant proportion of employees, about 14%, take time offfrom their jobs due to pain conditions. In hospitalizedpatients, pain has been associated with increased length ofstay, longer recovery time, and poorer patient outcomes, allof which have health care quality and cost implications(NINDS and others 1998).

It is also clear that progress in understanding and allevi-ating pain in humans and animals requires the use of ani-mals. Only live animals feel pain and behave in ways that aresimilar to humans' behavior when experiencing pain. Painresearch in animals has been essential in improved under-standing of the neural basis of pain and the "development ofbetter narcotic and nonnarcotic analgesic drugs, the intro-duction of pain-relief procedures using electrical stimulationof peripheral nerves, sensory pathways or neural centers inthe brain, and the recognition and exploitation of endogenouspain-suppressing chemicals such as enkephalines in thebrain" (Sessle 1987, p 75-76). Improved understanding ofand ability to deal with pain require continued research on

animals (Bonica 1992; Dubner 1983, 1987; Sessle 1987;Sternbach 1976; Zimmermann 1986).

Unfortunately, it is often impossible to do pain researchon animals without the animals experiencing pain. Someimportant knowledge regarding pain mechanisms and modu-lation has been gained from studies on animals that cannotfeel pain because they have been anesthetized or renderedunconscious by decerebration or decortication. However,much of what needs to be known requires awake and con-scious animals, especially in research on pain neurophysiol-ogy at levels above the spinal cord (Dubner 1987; Sessle1987; Zimmermann 1986). Although some pain studies canallow animals to escape or to avoid painful stimuli when theypresumably become too uncomfortable, several areas of painresearch require unavoidable painful experiences. Someresearch into pain-suppressing pathways and mechanismsrequires activation of painful and nonpainful stresses, includ-ing inescapable noxious stimuli. Studies of chronic pain oftenrequire experiences of pain and can involve such techniquesas intermittent or continuous electrical stimulation of nervesor tissues; manipulation of nerves and tissues to producechronic pain such as induction of neuromas or intradermalinoculation of bacterial toxins; and changes in sensory path-ways by such methods as peripheral nerve deafferentiation,production of lesions, or injection of convulsive drugs,toxins, and chemicals resulting in neural hyperexcitability(Dubner 1987; Sessle 1987; Zimmermann 1986). Animalmodels that can involve unrelieved pain include some foramputation pain (Blumberg and Janig 1982; Wall andGutnick 1974), arthritis pain (Coderre and Wall 1987;Colpaert 1987; DeCastro Costa and others 1981), cardiacpain (Uchida and Murao 1974), chronic pain (Sweet 1981),deafferentiation pain (Brinkus and Zimmerman 1983;Wiesenfeld and Lindblom 1980), muscle pain (Mense andSchmidt 1974), neuropathic pain (Bennett and Xie 1988),stress-induced analgesia (Lewis and others 1980), trigeminalneuralgia (Black 1974), and visceral pain (DeLeo and others1992).

Pain research thus places us between horns of a trouble-some ethical dilemma (Dubner 1983; Zimmermann 1986).We appear obligated to do something—pain research on ani-mals—that will sometimes involve doing something else—causing pain—that we are generally obligated not to do. Todo great good we must sometimes cause great harm. Andalthough causing such harm may often be justified, the natureof the needed justification sometimes makes the ethicaldilemma more troublesome: As the problem of pain forhumans and animals becomes greater, the pain we can justifycausing animals when they are used in valuable pain researchincreases. Moreover, although the Minimization Principleapplies even when pain is justifiably inflicted on animals, inpain research this principle may often fail to accomplish itsultimate goal, which is to spare animals significant or sub-stantial pain.

None of this means that it is inherently wrong to causeanimals pain in pain research. However, as Feinberg (1980, p194) observes, although causing "some pain does more good

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on balance . . . what follows is that justifiable pain is a neces-sary evil, not that some pain is good in itself." That causinganimals pain, even when justified, is a necessary evil explainswhy we should be unhappy about the need to do it and whywe should feel unsettled by it (which is not the same assaying we should feel guilty about doing it). That causinganimals pain in pain research may sometimes be a necessaryevil also implies that IACUC members and investigatorsmust pay special attention to their ethical obligations of mini-mizing harm to animals.

Ethical Guidelines for lACUCs

In the following enumerated recommendations, I use thegeneral ethical principles defended above to propose ethicalstandards for IACUC members in their consideration of painresearch. These recommendations are provided to assist com-mittees and scientists in developing their own approaches.Although intended specifically for use by committees asrequired by laws and regulations in the United States, therecommendations, like the general ethical principles onwhich they rest, are universally applicable. I assume, how-ever, as a given that the interests of research animals and ofthe general public in assuring the appropriate use of animalsrequire that animal research proposals be reviewed forhumaneness by local institutional committees.

1. The IACUC should apply to the consideration of anypain research proposal the fullest and most complete con-sideration available under its operating procedures. Be-cause the deliberate infliction of animal pain is the inflictionof a fundamental harm and evil, an IACUC should take allreasonable steps to assure that any pain research on animalsperformed at the institution is ethically appropriate, withoutquestion. There should not be expedited review of suchresearch, nor review by a delegated member, committee, orsubgroup of the IACUC. So that the best scientific, technical,and ethical questions can be asked, all members of theIACUC should attend the review of pain research proposals.It is especially important for all nonaffiliated members to bepresent. The principle that animals should not be caused un-necessary pain is a deeply held ethical standard of the public,and pain research is typically justified on the grounds that itbenefits the public. The community representatives on theIACUC should be available to apply this ethical standard andconsider the sufficiency of this justification. Unaffiliated andcertainly nonscientist members are also likely to insist ondescriptions of any pain the animals may experience in layterms that not only are understandable to them but also reflectthe public's concern about what animals might actually feel.If necessary, an expert consultant should be invited to assistthe committee if members require additional knowledgeregarding pain research or mechanisms of pain avoidance,alleviation, or minimization. In light of the ethical signifi-cance of deliberately causing animals pain, any animal painresearch must receive meticulous review by a committee,

even if the research is not covered by federal laws and regu-lations because the institution does not receive PHS fundsand the work is done on species currently not subject to USDepartment of Agriculture regulation.

2. Any proposal of pain research in animals should containclear and convincing statements of the justification andvalue of the research, including the relevance of the workto practical benefits or important theoretical knowledge,the soundness of the science, and the competence andability of research and animal care personnel to monitorand minimize animal pain. The greater the pain experi-enced by the animals, the greater must be the justificationand value of the research. Because of the obvious generalneed for pain research, some investigators and IACUCs maybe tempted to settle for quick, boilerplate justifications ofexperiments that assert in the most abstract terms the impor-tance of pain and pain research. However, such statementsare unacceptable. An investigator should explain to theIACUC what kind or kinds of pain are being investigated,why such pain is in great need of understanding or allevia-tion, and how it is hoped that the proposed research willcontribute to this process. Because of the clear ethical cost ofinflicting pain, investigators must be prepared to demon-strate knowledge of any experiments or tests that are similaror related to their proposed experiments and to show thattheir work is designed to verify or contribute relevant andimportant knowledge.

There is disagreement among IACUCs and commenta-tors about whether committees can and should consider thescientific soundness of research proposals (Prentice andothers 1992; Tannenbaum 1995, p 495, 501). In my view, itis obvious that an IACUC must assure itself to at least someextent of the scientific soundness of research that will causeanimals pain. It is difficult to imagine an IACUC respondingto an experiment that would cause a large number of animalsconsiderable and long-lasting pain with the statement that"we know there will be great pain here but we must leave itcompletely to a study section (initial review group) to decidewhether there is any scientific or practical reason to do thiswork," or "we know that there will be great pain here but wecannot express any position on whether there is a good scien-tific reason to cause this pain." I believe that such responsesare as unacceptable as they would be unusual. US laws re-quire IACUCs (and not someone else) to determine whetherproposed animal experiments are humane (that is, ethical).Infliction of pain cannot be ethical unless it is justified, andan IACUC that is unwilling to undertake any considerationof the scientific or practical reasons for inflicting pain simplycannot determine whether that pain is justified.

In assuring that proposed research is likely to be suffi-ciently sound to justify infliction of pain, an IACUC may askthe principal investigator to demonstrate familiarity with painresearch. Students, research associates, and less experiencedinvestigators who propose or work on animal pain researchexperiments should either demonstrate sufficient knowledgeof pain research and the value of a proposed experiment that


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will cause animals pain or be closely supervised by a scien-tist with such knowledge. The IACUC should assure that theinvestigator and other personnel who work on an experimentthat will cause pain are knowledgeable regarding methods ofassessing and alleviating pain; otherwise, even the most jus-tifiable experiment could result in unnecessary pain.

3. IACUCs should encourage investigators to demonstratein experiments that will cause animals pain or distress alevel of justification and value that is as high as possible.Estimating animal pain is and will likely always be impre-cise. Moreover, it is sometimes difficult to estimate thepotential theoretical and practical benefits of scientificexperimentation. Some experiments fail, and much basicresearch has brought practical results that could not havebeen predicted at the time it was done (Comroe and Dripps1976). There are significant conceptual issues regarding howto define such states as pain, distress, discomfort, and anxi-ety in animals (Tannenbaum 1995, p 416-418; Wall 1992).People disagree on ethical grounds whether certain kinds ofresearch justify animal pain or some degree of animal pain.

In light of these uncertainties and controversies, thehigher the level of justification and value of the research aninvestigator can demonstrate, the easier it will be for theIACUC to feel confident in the ethical appropriateness of thework—because the uncertainties and controversies becomeless likely to affect the final decision whether a piece ofresearch is ethically justified. An experiment that is part of ageneral research program that has already led to medicallysignificant improvements in treating pain and is proposed bya scientist with demonstrated expertise and success in thearea will likely overcome issues regarding precisely howmuch pain is being produced, whether the animals are feel-ing some distress as well as pain, or whether the negativefeelings experienced by the animals will be absolutely mini-mized. If the research has great value, what the animalsexperience will probably be viewed as justified, providedthat all reasonable steps are taken to try to minimize theirpain and distress.

4. Investigators should characterize and estimate the likelypain and associated negative feelings that will be experi-enced by the animals as completely and accurately as rea-sonably possible. Investigators and IACUCs should con-sider a wide range of evidence, including inferences fromsimilar pain experiences in humans and the best availablescientific data regarding behavioral and physiological signsof animal pain. To determine that the research is justified,the IACUC must try to determine when the pain will startand end, how intense it is likely to be, and any other informa-tion about its phenomenological character. Investigatorsshould assure the IACUC that they know how to assess andcharacterize pain in animals. Investigators should be familiarwith normal behavior patterns in species in which they causepain and with the kinds of deviations from such behaviorsthought to be associated with pain (Morton and Griffiths1985; Sanford 1992; Sanford and others 1986; Soma 1987;

Spinelli 1987; Spinelli and Markowitz 1987; Wright andothers 1985). As a number of prominent animal painresearchers and specialists argue, one should not reject allanthropomorphism in describing the pain of animal subjects(Dubner 1987; Soma 1987; Zimmermann 1986). The pur-pose of most pain research is to understand pain in humans,and it is often scientifically reasonable to assume that whatthe animals feel is similar to what humans feel.

Numerous schemes for scoring various levels or severityof animal pain have been proposed to assist IACUCs andinvestigators in estimating and minimizing pain. Some ofthese (Orlans 1993, p 87-88; SCAW 1987; Swedish Classifi-cation for Research Techniques 1984) were devised in anattempt to correlate levels of pain with standard kinds ofsurgical or experimental procedures. Others (DeLeo andothers 1992; Morton and Griffiths 1985) specify kinds ofanimal behavior that are presumed reflective of levels ofpain. They direct investigators to locate what animals feel inan appropriate pain level category on the basis of observedbehavior.

Investigators should also consider the possibility that painin animals may sometimes be worse for them than pain inhumans experienced under similar circumstances. Becauseanimals may not know (or be able to know) why they aresuffering pain or that the pain will end, pain may so com-pletely dominate the animal's psychology that it may some-times be appropriate to view its entire life for some period oftime as a painful experience—as Rollin (1989, p 60) aptlyputs it, to view the animal as its pain. Analogizing fromhuman experience may sometimes increase the estimate ofexpected harm to animals and thereby increase the level ofrequired value of an experiment. For example, people whoexperience relatively low levels of pain for extended periodsof time can become annoyed, depressed, and unhappy—theycan suffer—because of the seemingly unending pain. Thetotal negative experience can be worse than if one consid-ered just the intensity and duration of the pain itself. Althoughone must be careful imputing to animals sophisticated emo-tional reactions to pain, neither should one preclude thepossibility of such reactions.

The International Association for the Study of Pain(IASP1) recommends that in pain research on conscious ani-mals for "most non-invasive stimuli causing acute pain," theinvestigator "should try the pain stimulus on himself(Zimmermann 1983, p 109). As a nonscientist, I cannotassess the general validity of such an approach in estimatinganimal pain, but I can report an incident in which severalmembers of an IACUC asked to receive an electric shock(not part of a pain study) that an investigator proposed togive to rabbits. They found the stimulus, when repeatedseveral times as would have occurred in the experiment, sodistressing that they asked the investigator to convincinglydemonstrate the value of the research. (The investigator with-drew the proposal.) Perhaps IACUC members as well asinvestigators can try certain proposed painful stimuli onthemselves if knowledge about the species and individualsused does not cast doubt on extrapolation of human reactions

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to what may be experienced by the animals. It might also behelpful for IACUC members to view animals that are sub-jected to painful procedures either before approving a pro-posal if possible or afterwards so that members can assurethemselves that pain experienced by the animals is justified.

The IASP also recommends that pain studies "in animalsparalyzed with a neuromuscular blocking agent should notbe performed without a general anesthetic or an appropriatesurgical procedure that eliminates sensory awareness"(Zimmermann 1983, p 110). This recommendation is sup-ported by one of its authors on the grounds that because suchanimals "can be considered to be under stress in the condi-tion of neuromuscular paralysis," any results obtained"would be of no scientific value" (Zimmermann 1986, p231). Additionally, paralysis removes overt signs of pain anddistress and therefore removes one of the major ways todetermine the severity, duration, and character of the ani-mals' pain and distress. Because it is difficult if not impos-sible to characterize what paralyzed animals feel, one cannotdetermine whether what they feel is justified, whether theirpain and distress is being minimized relative to the aims ofthe experiment, and whether their pain and distress havebecome so severe that the experiment must at some point beterminated.

5. Investigators should assure the IACUC that they areattempting to minimize pain in the design and performanceof the research. Investigators should bear the burden ofdemonstrating to the IACUC why pain-relieving tools suchas analgesia, pain avoidance, and environmental enrich-ment cannot be used, consistent with justified experimentalaims. The veterinary and animal care staff must assure thatprocedures for pain minimization approved or required bythe committee are followed. As Dubner (1987) explains,there is a range of techniques in animal pain research that areassociated with different amounts or degrees of pain. Experi-ments on completely anesthetized animals, which haveyielded some significant knowledge, cause no pain and donot raise ethical issues relating to whether pain is justified.Procedures on awake animals that have been given analgesicagents cause minimal pain or distress and can be relevant tocertain kinds of information on, for example, neural pro-cesses minimally affected by such agents. Some animal painresearch involves causing pain to animals that is not relievedbut that can be escaped by avoidance behavior (such as tail-flicking or avoiding a painful stimulus) or administration ofpain relief by the animal. Experiments involving physicalrestraint of animals can be quite stressful. The level of stresscan sometimes be reduced by training the animals to performpain detection and pain discrimination tests by, for example,having the animals decide when to initiate the test and whento withdraw from the experiment by ceasing to initiate trials.Experiments in which animals experience unrelieved paininclude induction of acute pain of varying levels of severityas well as chronic pain of varying levels of severity andduration.

The Minimization Principle requires investigators to try

to design research as far toward the pain-free end of thisrange of techniques as possible, consistent with justifiedexperimental aims. IACUCs should therefore ask investiga-tors to provide scientific reasons why the research cannot beof a sort that might cause less pain. Even when an experi-ment is appropriately designed, the investigator should assurethe IACUC that all reasonable attempts will be made to mini-mize pain. Thus, in acute or chronic pain studies, the painshould not last longer than is required and should be allevi-ated with analgesics whenever or as soon as doing so isconsistent with experimental aims. Animals should beallowed to avoid, self-treat, or escape pain when consistentwith justified experimental aims. Environmental enrichmentand opportunities for species behavior associated with stressreduction can lessen stress and discomfort experienced bythe animals (Mench 1998; Zimmermann 1986).Zimmermann (1986, p 230-231) recommends that "animalsin a chronic pain state should not be left alone. Whereverpossible they should live in a rich environment providingsocial interaction with members of their own species, andmuch attention and handling by the scientist and his associ-ates. There are indications that animals in pain suffer lesswhen socially rewarded."

Zimmermann (1986, p 225-226) illustrates how applyingthe Minimization Principle can offer both possibilities anduncertainties. The leading model for amputation paininvolves production of neuromas in rats and cats. After aperipheral nerve is transected under general anesthesia, thenerve fibers in the proximal stump begin to regenerate. Thisregeneration can cause severe pain, classified in humans asneuropathic pain. Rats and monkeys on which this procedureis done scratch and bite the denervated limb; the degree ofself-mutilation is viewed by some scientists as a measure ofthe degree of pain. However, when a small nerve is lesioned,there is no self-mutilation, which appears to support the con-clusion that there is no or minimal pain even though theneuropathophysiology has fully developed. Thus, there maybe a way of doing this research that does not involve substan-tial pain. Nevertheless, because there is evidence that self-mutilation seen after nerve lesions is not always a sign ofpain in animals, more work is needed to determine reliablecriteria of pain so that we can accurately estimate the ethicalcosts of this kind of pain research.

Procedures that allow animals to escape pain have pro-vided important data and would ordinarily be preferable tothose that inflict unrelieved pain. However, it is not the casethat, as suggested by Sessle (1987, p 76), such techniquesraise no ethical issue, because ethical guidelines governingpain research in humans approve of painful stimuli thathuman subjects can avoid or terminate at will (Charlton1995). Animals do not have the same kind of appreciation ofwhat they are experiencing that can render it less stressful;they do not choose to be subjected to pain; and they cannottell us that once they avoid or terminate a stimulus, their painhas ended. Although procedures that allow animals to escapeor terminate pain may usually be less ethically problematicthan those involving unrelieved or continuous pain, the in-


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fliction of even temporary pain is still the infliction of painand must have sufficient ethical justification.

The Justification Principle requires anyone who causesanimals pain to provide justification for doing so. The burdenof providing sufficient justification should therefore be onthe investigator and not the IACUC. Moreover, the likeli-hood of minimizing animal pain will probably be increasedif, as a general policy, an IACUC asks investigators whocause animals pain to show why there is not some means ofcausing less pain consistent with justified research. Such apolicy puts investigators on notice that they are always ex-pected to try to minimize pain.

The Minimization Principle must be applied beyond con-sideration of research proposals by the IACUC. Pain can beminimized only if veterinary and animal care staff conscien-tiously and competently assure that the minimization proce-dures approved or required by the IACUC are followed.

6. In balancing pain and distress caused to animals againstthe value of the research, and in monitoring pain researchin progress, the IACUC should consider whether pain hasbecome so severe that individual animals should be re-moved from the research or the research itself should beterminated. At some point, the scientific reasons for a studymay simply not justify the pain experienced by some or all ofthe animals.

7. Pain in "lower" species may not be considered less harm-ful or in need of less justification than pain in "higher"species. The Equality Principle permits differences in speciesto be taken into account only when relevant to the amount orintensity of pain or the likely presence of other negativeexperiences or emotions such as distress, fear, depression, oranxiety, which can accompany pain in humans.

8. Investigators and IACUCs should focus on what is fairto individual animals, which may sometimes require length-ening rather than shortening the duration of pain, usingmore rather than fewer animals, or causing more ratherthan less total pain. The IASP recommends that "the dura-tion of the experiment must be as short as possible and thenumber of animals involved kept to a minimum"(Zimmermann 1983, p 110). Minimizing duration and num-bers may often lessen the burdens experienced by individualanimals used in pain research. However, fairness to indi-vidual animals may sometimes obligate investigators andIACUCs to consider alterations in experimental design thatmay increase or not lessen duration of pain or numbers ofanimals.

9. IACUCs should attempt to adhere to government ethicalrules and should consult relevant professional associationethical guidelines but should view all general rules andguidelines as calling for, and ultimately subject to, inde-pendent ethical deliberation. Aside from having the force oflaw, government ethical rules relating to pain in animalresearch reflect society's most fundamental ethical views

regarding animals. Ethical policies of professional researchassociations can provide unique perspectives of working sci-entists. However, laws often set forth minimal standards forbehavior, which one may sometimes be ethically obligatedto exceed. Both laws and professional association guidelinestend to be general and to fall back on general standards suchas the Justification, Value, and Minimization principles.Therefore, to assure the humaneness of pain research in ani-mals, IACUCs and investigators must engage in independentethical assessment of research. They must apply to particularresearch situations general ethical principles such as thosedefended in this article.

Ethical Guidelines in Current Lawsand Regulations

US federal laws, regulations, and policies governing animalresearch contain many ethical guidelines applicable to painresearch in animals. The AWA requires that regulations beeffected that assure "animal pain and distress are minimized,including adequate veterinary care with the appropriate useof anesthetic, analgesic, tranquilizing drugs, or euthanasia"(7 USC 2143(a)(3)(A)); that "the principal investigator con-siders alternatives to any procedure likely to produce pain toor distress in an experimental animal" (7 USC 2143(a)(3)(B));that "in any practice which could cause pain to animals," aveterinarian be consulted in the planning of such procedures(7 USC 2143(a)(3)(C)(i)) and that these procedures providefor "the use of tranquilizers, analgesics, and anesthetics"(7 USC 2143(a)(3)(C)(ii)); and that "the withholding of tran-quilizers, anesthesia, analgesia, or euthanasia when scientifi-cally necessary shall continue for only the necessary periodof time" (7 USC 2143(a)(3)(C)(v)). These provisions, all ofwhich express the Minimization Principle, are elaborated inregulations that reiterate and sometimes apply this principlemore concretely with, for example, the requirements that"procedures involving animals will avoid or minimizediscomfort, distress, and pain to the animals" (9 CFR2.31(d)(l)(i)); that investigators provide the IACUC a writ-ten narrative showing that they have considered "alternativesto procedures that may cause more than momentary or slightpain to the animals" (9 CFR 2.31(d)(l)(ii)); and that ananimal research proposal contain a "description of the proce-dures designed to assure that discomfort and pain to theanimals will be limited to that which is unavoidable for theconduct of scientifically valuable research, including provi-sion for the use of analgesic, anesthetic, and tranquilizingdrugs where indicated and appropriate to minimize discom-fort and pain to the animals" (9 CFR 2.31(d)(l)(x)). Otherprovisions of the AWA or regulations, which appear to havebeen intended at least in part to avoid unnecessary pain,include the prohibition of the use of paralytics without anes-thesia (7 USC 2143(a)(3)(C)(iv), 9 CFR 2.31(d)(l)(iv)); therequirement that animals "that would otherwise experiencesevere or chronic pain or distress that cannot be relieved willbe painlessly euthanized at the end of the procedure, or, if

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and distress that would not compromise experimental resultsmay be employed" (APS 1996, p i ) . The constituent societ-ies of the Federation of American Societies for ExperimentalBiology have adopted a Statement of Principles for the Useof Animals in Research and Education. These guidelines statethat "sound scientific practice and humane considerationsrequire that animals receive sedation, analgesia or anesthesiawhen appropriate. Animals should not be permitted to suffersevere or chronic pain or distress unnecessarily; such ani-mals should be euthanized" (FASEB 1994, p 2). This docu-ment also requires conformance with all applicable laws and,like the US Principles, states that "all work with animalsshall be designed and performed in consideration of its rel-evance to the improvement of human or animal health andthe advancement of knowledge for the good of society"(FASEB 1994, p 1). The Society for Neuroscience Policy onthe Use of Animals in Neuroscience Research recommendsand is based on the PHS Policies and the Guide, and it re-peats or paraphrases the requirements of the US GovernmentPrinciples: "the avoidance or minimization of discomfort,distress, and pain," including use of sedation, analgesia oranesthesia in procedures "that may cause more than momen-tary or slight pain or distress" (SFN 1997, p 2).

The American Psychological Association Guidelines forEthical Conduct in the Care and Use of Animals also requirecompliance with all laws and regulations but add a numberof more specific recommendations relating to animal pain.These recommendations include the statements that (1) be-havioral procedures "that minimize discomfort to the animalshould be used"; (2) when using aversive conditions, "psy-chologists should adjust the parameters of stimulation tolevels that appear minimum"; (3) "psychologists are encour-aged to test painful stimuli on themselves, whenever reason-able"; (4) "whenever consistent with the goals of the research,consideration should be given to providing the animals withcontrol of the potentially aversive stimulation"; (5) "proce-dures involving more than momentary or slight aversivestimulation, which is not relieved by medication or otheracceptable methods, should be undertaken only when theobjectives of the research cannot be achieved by othermethods"; and (6) "experimental procedures that requireprolonged aversive conditions or produce tissue damage ormetabolic disturbances require greater justification and sur-veillance. An animal observed to be in a state of severe dis-tress or chronic pain that cannot be alleviated and is notessential to the purposes of the research should be euthanizedimmediately" (APA 1992, p 5). This last statement embodiesthe requirements of the Justification and Value Principlesthat the pain or distress to which animals are subjected mustbe proportional to the justification and value of the experi-ment. The American Psychological Association Policy reit-erates these principles in its general requirements of justifi-cation for the use of animals in proposed experiments, whichinclude the statements that

Research should be undertaken with a clear scientific pur-pose. There should be a reasonable expectation that the

research will a) increase knowledge of the processes under-lying the evolution, development, maintenance, alteration,control, or biological significance of behavior; b) deter-mine the replicability and generality of prior research;c) increase understanding of the species under study; ord) provide results that benefit the health or welfare ofhumans or other animals (APA 1992, p 2);

and

The scientific purpose of the research should be of suffi-cient potential significance to justify the use of animals(APA 1992, p 2).

IASP Ethical Guidelines

In 1980, the Committee for Research and Ethical Issues ofthe IASP issued a set of ethical standards for use of animalsin experimental pain research (Covino and others 1980).These guidelines were revised in 1983 (Zimmermann 1983).The preface to the current guidelines state that investigators"should make every effort to minimize pain" and should"accept a general attitude in which the animal is regarded notas an object for exploitation, but as a living individual"(Zimmermann 1983, p 109).

The 1983 IASP guidelines are contained in Table 1. Sev-eral of the guidelines have already been discussed in thispaper. The first guideline endorses the Justification and Valueprinciples and appears to allow ethical evaluation of evenscientifically sound research. The IASP guidelines requirethat investigators demonstrate likely practical benefits ofexperiments by showing their relevance to pain therapy. Ihave suggested that a stronger showing of the importance ofa piece of basic research must be made when that work wouldcause pain or discomfort to animals than when researchshows prospects of providing medical benefits (Tannenbaum1995, p 472). However, I have not built this principle or therequirement that pain research causing animal pain mustpromise practical benefits into my recommendations toIACUCs. There has been very little consideration in the lit-erature of the ethics of causing animal pain in basic research,and our understanding of this issue could benefit from addi-tional discussion. The 1980 IASP guidelines contained thestatement that "the investigator should choose a specieswhich is as low as possible in the phylogenic order, compat-ible with the aim of the investigation. This recommendationinfers that the degree of suffering is smaller in lower than inhigher animals although this assumption cannot be taken asproven" (Covino and others 1980, p 142). The 1983 guide-lines wisely deleted this statement. Although the EqualityPrinciple is consistent with using "lower" species if they doexperience less pain or suffer less, allowing investigators toproceed on the basis of an unproved assumption could rein-force the notion that the experience of pain in "lower" ani-mals is less real or less ethically relevant.

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Table 1 Ethical Guidelines for Investigations ofExperimental Pain in Conscious Animals of theCommittee for Research and Ethical Issues of theInternational Association for the Study of Paina

(1) It is essential that the intended experiments on pain inconscious animals be reviewed beforehand by scientistsand lay-persons. The potential benefit of such experimentsto our understanding of pain mechanisms and pain therapyneeds to be shown. The investigator should be aware of theethical need for a continuing justification of his investigations.

(2) If possible, the investigator should try the pain stimuluson himself; this principle applies for most non-invasivestimuli causing acute pain.

(3) To make possible the evaluation of the levels of pain,the investigator should give a careful assessment of theanimal's deviation from normal behavior. To this end,physiological and behavioral parameters should bemeasured. The outcome of this assessment should beincluded in the manuscript.

(4) In studies of acute or chronic pain in animals, measuresshould be taken to provide a reasonable assurance that theanimal is exposed to the minimal pain necessary for thepurposes of the experiment.

(5) An animal presumably experiencing chronic pain shouldbe treated for relief of pain, or should be allowed to self-administer analgesic agents or procedures, as long as thiswill not interfere with the aim of the investigation.

(6) Studies of pain in animals paralyzed with a neuromuscularblocking agent should not be performed without a generalanesthetic or an appropriate surgical procedure thateliminates sensory awareness.

(7) The duration of the experiment must be as short aspossible and the number of animals kept to a minimum.

aReprinted from Pain, Vol. 16, M. Zimmermann, "Ethical guidelinesfor investigations of experimental pain in conscious animals,"p 109-110, 1983, with permission from Elsevier Science.

Conclusion: The Work Ahead

To an animal, it does not matter whether its pain or distress is

part of research designed to understand and treat pain. More-

over, because pain research is but one kind of biomedical

research, animals that feel pain as a result of pain research

surely represent a small fraction of research animals that feel

pain or distress. Pain research, however, can lead the way in

our general approach to ethical issues relating to pain in

research animals. IACUCs and investigators cannot avoid

confronting the reality of animal pain in experiments that

intentionally cause such pain. They must engage in ethical

deliberation in which animal and human interests are care-

fully balanced. They are ethically and legally obligated to

find and implement techniques of lessening animal pain.

Such ethical deliberation and such techniques for pain mini-

mization will surely be applicable to animal pain associated

with other kinds of research.

To help the countless people and animals that suffer pain,

we need more pain research. The ethical paradox of pain

research—that the evil of pain must sometimes be caused to

ultimately understand and alleviate it—is for now inescap-

able. We owe it to the animals to approach the ethics of pain

research as seriously as we approach the science.

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