Palmer College of Chiropractic

Chiropractic Research

Questions and Answers about Research Using Laboratory Animals at Palmer Chiropractic University

We believe that objective, informed and responsible dialogue is important to the Palmer community. We fully realize that animal research is a sensitive issue that tends to polarize people, and we are hereby providing detailed information about Palmer’s research program that we hope will advance the understanding of how animal research contributes to the advancement of chiropractic and patient care. It will be impossible for the chiropractic profession to fully realize its positive potential for humankind without rigorous basic science research. This is the kind of research that has brought significant health care advances to humans and animals, and it is a key part of the profession’s maturing ability to take responsibility for continuously improving its clinical care and patient outcomes.

Additional information can be found at: Understanding_research_06_24_03.htm

And: Animal_links_06_24_03.htm

Are laboratory animals involved in Palmer’s research?

Humans and animals are both involved in different aspects of Palmer’s research effort. Human subjects are involved in many clinical studies while rats and cats, specially bred and purchased for laboratory use, are involved in basic science studies designed to understand the underlying neural and biomechanical aspects of subluxation and adjustment. The overarching goal is to improve healthcare for the public.

How many laboratory animals are being used in Palmer’s research?

The U.S. Office of Technology Assessment estimates that 17-23 million animals are used in the U.S. each year in research. The majority are rats and mice. In 2000, 95,500 dogs and cats were used in research (USDA Animal Care Report, 2000). Over five (5) years 140 rats and approximately 600 cats will be involved in ground-breaking chiropractic studies at Palmer. To put these numbers in perspective, consider that biologists estimate that over one million animals are killed every day by vehicles, over 365 million per year (Wall Street Journal, August 1, 2002). The American Humane Association estimates that animal shelters and pounds put 10-17 million abandoned pets to death each year, mostly dogs and cats.

Is the use of laboratory animals new in chiropractic research?

No. The use of laboratory animals in chiropractic research goes back at least 45 years (e.g. see: Cleveland, 1965; Sato, 1984; Lin, 1978). This is well documented in Gatterman’s chiropractic textbook Foundations of Chiropractic: Subluxation (Gatterman, 1995). Twenty years ago chiropractic scientists at Palmer initiated studies documenting the effect of subluxation on gastric function in rabbits (DeBoer, 1984, 1988a, 1988b). In 1997, a consensus of chiropractic scientists affirmed the importance of basic science, including the development of animal models (Brennan, 1997). Valuable original research using laboratory animals is currently being sponsored at a number of chiropractic colleges including Palmer, Canadian Memorial Chiropractic College, Parker College of Chiropractic, and National University of Health Sciences.

Why is PETA attacking Palmer’s research?

It’s simple. PETA is attacking Palmer because we use laboratory animals in some of our research studies. PETA does not really care about how well we treat our laboratory animals because PETA is unalterably opposed to the use of animals in research for any and all reasons whatsoever. PETA is also against the use of animals for food or clothing, or as pets (http://www.peta.org/about/index.html). In fact, PETA is against the use of animals for any human purpose of any kind. PETA does not seem to recognize that any good has arisen, or can arise from research using animals. (Ironically, health care research using animals and humans benefits both animals and humans alike.)

In a letter dated last November 2002, PETA threatened to “do everything in our power to stop you.” PETA will never stop attacking Palmer as long as laboratory animals are used, regardless of the significance of the research and despite the fact that all such studies adhere to extremely stringent regulations and ethical guidelines for humane care. We also suspect that PETA is attacking Palmer and the chiropractic profession because they perceive us as weak. We note that many, many research institutions with much larger animal research programs are ignored by PETA. Why doesn’t PETA attack the 125 medical schools in the U.S.?

Why can’t you use other research methods, such as computer models, etc?

Palmer has adopted a code of ethics that requires a complete scientific justification for the use of laboratory animals. The same criteria are also applied by Palmer’s independent Institutional Animal Care and Use Committee (IACUC) and the U.S. Office of Laboratory Animal Welfare (OLAW). This means that animals can only be used if there are no other means to address the scientific questions. Three strict criteria must be met: 1) the research cannot be pursued by any other means, 2) there must be complete justification for the animal species being used, and 3) only the minimum number of animals must be used. This means that before any project is approved, the investigators must search for alternatives to using animals and document the rationale for using them.

PETA says that our animal studies are “useless,” but this is wrong. Our studies have been funded by grants from the prestigious U.S. National Institutes of Health (NIH) (website). At NIH, all grant applications are critiqued by a committee of scientific peers and ranked according to quality and scientific importance. The NIH, National Center for Complementary and Alternative Medicine (NCCAM) (http://nccam.nih.gov), which funds our work, only awards 15% (1 out of 6) proposals submitted to it. This means that world famous neurophysiologists, biomechanists, statisticians, chiropractors, and other health care practitioners have examined our research methods and goals and found them worthy. Furthermore, what could be more important to the chiropractic profession than fundamental research on the underlying principles of chiropractic theory and philosophy!

It has been suggested that we use computer models, other kinds of simulations and convicted criminals instead of rats or cats. Understandably, animal research is extremely difficult and costly, but the truth is that there are no models, computerized or otherwise, that can be used to answer the fundamental questions about subluxation and adjustment at this point in our scientific development. We cannot do certain kinds of physiological research using humans because it would be unethical and illegal. Criminals are legally protected by the same federal regulations as any other human subject involved in research. Furthermore, most all biological computer models were originally built on data from animal studies. Models by their very definition must be based on some validated knowledge of the phenomena under study. In the absence of such basic knowledge, models do not exist. Much of what we learn from today's animal models in research may yield data that will eventually allow us to create a mathematical finite element model of the spine. At some point in the future with additional data, computer models and the like may become validated and useful for chiropractic research.

What studies are using rats and why are they important?

Rats are being used to develop a model of spine fixation that permits direct examination of the nature and consequences of spine subluxation and chiropractic adjustment. The most exciting feature of this model is that it enables us to evaluate biological effects predicted by chiropractic theory. In addition, we may use the model to directly examine important clinical questions: Is there a ‘time window’ when spinal adjustment is most effective? What are the effects of different chiropractic techniques? What is the effect of repeated adjusting under differing biomechanical and pathological states of a subject? Can the subluxation alter visceral function and can it be reversed?

This model uses very small spinous attachment units (SAUs) that are surgically implanted in the lumbar vertebrae of laboratory rats. The stems of the SAUs extend through the skin, similar to standard fracture fixation devices used in humans (e.g. Halo device for fractured cervical vertebrae). External fixation devices do not cause discomfort. The implants allow subsequent induction of spine fixation and malposition by linking the externally located stems of the SAUs in various positions, for example in slight flexion, extension or rotation. After varying time periods, the external links are removed. Results show that there is a residual hypomobility and malposition—cardinal biomechanical features of the subluxation. These experimentally induced subluxations may then be assessed for biological effects and treated with spinal adjustments.

During the SAU implant surgery the rat is under general anesthesia and aseptic surgical procedures are followed at all times. The corneas are protected from drying during the procedure and core body temperature is maintained by a homeothermic blanket system. These procedures are very similar to those used in human back surgery, designed to be as minimally invasive as possible. Buprenorphine analgesic is administered at the conclusion of the surgical procedure and Ketoprofen impregnated Jell-O is also provided for at least two post-surgical days or as needed. Pain behavior of any kind is very rare following this procedure (less than 2%). At the conclusion of all studies with this model, sleep is induced in the rats with gas anesthesia and each animal is euthanized by C02 inhalation. This method is non-traumatic and consistent with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association. All of our procedures are designed and approved under the supervision of Palmer’s Board Certified Laboratory Animal Veterinarian.

To date, we have developed and evaluated the feasibility of this model to provide a useful platform for studying fundamental mechanisms ascribed to the subluxation. Our early findings are that experimentally induced spine fixation is greater for longer link periods, with a critical time threshold occurring between 4 and 8 weeks. Spine stiffness increased markedly after the four- and eight-week link periods (compared to one week, two week, 12 week, and 16 week link periods). Also of great interest was the observation that residual spine stiffness following each of the six link durations continued to increase—even after the external links were removed. This suggests that a self-perpetuating pathological process begins within one week of linking (the shortest link period). Studies currently underway are examining the ability of spinal adjustment to interrupt that process. These observations are consistent with those of chiropractors in practice.

In addition, work with the model has demonstrated degenerative zygapophysial joint (Z-joint) changes. Our preliminary work has been presented at several scientific conferences and was recently accepted for publication (Cramer, 2003, 2000; Henderson, 1999, 2000). Changes found in vertebral segments that were experimentally fixed were compared with changes in adjacent non-fixed vertebral segments within the same animals, and changes among fixation animals were compared with non-fixed (control) animals. Significant Z-joint changes were observed, for both osteophyte formation and articular surface degeneration when comparing control and fixation animals. It was also noted that fixed segments had more frequent and severe z-joint osteophyte formation and articular surface degeneration than non-fixed segments within the same animal. Both the frequency and severity of osteophyte formation and articular surface degeneration related to the duration of the link period. Lastly, the same critical time threshold occurring between 4 and 8 weeks for measurements of spine stiffness were observed with Z-joint degenerative changes. These are exciting results because degenerative arthritis is such a problem in human beings and is the hypothesized result of a hypomobile subluxation. This model provides the basis to study exactly how and to what extent chiropractic care may be able to arrest, reverse or prevent the degenerative process.

PETA continues to imply that Palmer cuts the legs and tails off the rats. Is this true?

No. PETA had obtained a grant proposal from Palmer that had originally discussed this methodology at one time. However, during the almost year long period of scientific review at NIH, new studies were published describing a new behavioral model of rat bipedalism. When these became known to NIH program officers and Palmer investigators, the protocols were changed. We have no plans to use the old surgical bipedal model, even though it has been used extensively in the past in spine research (over 30 references available upon request).

What studies are using cats and why are they important?

When D.D. Palmer founded and named chiropractic in 1895, his ability to formulate the art and philosophy of chiropractic was built upon knowledge from the science up to that time. Even then, chiropractic science was based upon experiments in both humans and animals. Only 10-20 years before chiropractic was founded Volta, doing an animal experiment on frog legs, found that something electrical flowed or was transmitted through nerves that made muscles move. Chiropractic knowledge of and understanding about how what we do works, will flourish when more individuals investigate the physiological mechanisms that contribute to the inherent recuperative powers of the body, and the way the spinal adjustment impacts those mechanisms. It is through this knowledge that we will be able to improve the care of our patients.

The goals of Palmer’s neurophysiology research laboratory are to increase our understanding of the physiological processes that give rise to the chiropractor’s analysis of a subluxation and to determine if and how spinal adjustments affect the nervous system. That the biomechanical act of performing a spinal adjustment alters the nervous system has been the hallmark theory of chiropractic since its inception. Yet, little in terms of demonstrating, quantifying and understanding just how and what parts of the nervous system are affected has been accomplished in the past 100 years and shared with the scientific and healthcare community.

Cats are used in our neurophysiology research for 3 reasons: 1) Cats have been used extensively by neurophysiologists for many decades to understand basic neural mechanisms because their nervous systems are very similar to humans. For example, our understanding is of the simple stretch or knee jerk reflex is based on cat studies performed by CS Sherrington between 1900 and 1920. 2) Cats are just sufficiently large enough in size to be able to perform experiments to investigate the relationship between the spine and the nervous system. 3) These experiments are impossible to perform on humans, and other laboratory animals such as rats and mice are too small.

The vertebral column poses a unique challenge for neurophysiological /biomechanical studies into chiropractic. Experimental techniques typically used to measure neural activity often necessitate the removal of paraspinal tissues, the very tissues in which we as chiropractors are interested. We have overcome this problem by developing a model that leaves the innervated paraspinal tissues intact but gives us access to the nervous system. We are now able to record the activity of single nerve cells contained in lumbar dorsal roots, a significant accomplishment.

All cats we use are treated in accordance with the Guiding Principles in the Care and Use of Animals approved by the American Physiological Society. Cats are anesthetized using a gas anesthetic similar to use in veterinary offices and hospitals for humans. The procedure was developed with a veterinary anesthesiologist. All experiments are conducted only when the animals have reached a level of surgical anesthesia and are completely insensible to painful stimuli. Blood pressure, heart rate, end-tidal carbon dioxide and metabolic status are monitored regularly and adjustments are made to keep the animal stable and physiologically similar to what would be done in veterinary or human surgery.

With the cat anesthetized and using careful and exacting surgical procedures, the dorsal roots innervating the paraspinal tissues of L6 are uncovered. We take advantage of the anatomical fact that the L6 dorsal root enters the spinal cord 2-2.5 vertebral segments rostral to its passage through the intervertebral foramina. In this way the paraspinal tissues innervated by the L6 dorsal root remain fully innervated. To apply mechanical loads to the spine, similar to those used in chiropractic practice, we attach modified tweezers to the spinous process of L6. The tweezers in turn are attached to motorized lever arm through which we can control the amount of force, the line of drive, and the depth of drive, the 3 factors all chiropractors are taught to control through their adjustive training. The values we use are similar in magnitude to those used by chiropractors as described in the research literature. The types of questions we are answering using these experimental procedures include, among others: 1) how does the speed and other biomechanical components (e.g. force/time profile) of a spinal adjustment affect neural responses? 2) how does vertebral position affect the sensitivity of muscle spindles? At the end of the experiments the animals are euthanized with anesthetic, never having woken up from the surgery and never having experienced any pain from the surgery.

This model has already proven valuable for elucidating heretofore unknown reactions of nerves contained in paraspinal muscles and joints to spinal adjustment forces. This research is demonstrating that adjustments certainly affect the nervous system, but in complex and interesting ways that will eventually allow chiropractors to increase their clinical effectiveness. All of this research is published in scientific journals for all to examine (Pickar, 1999; 2000, 2001a,b; Kang, 2001, 2002, 2003; Sung, 2003).

Are you causing pain to these animals to study the effects?

No. Palmer has been accused of intentionally causing pain in laboratory animals to study the effects. As the descriptions above should clearly demonstrate, these experiments are not done to study the effects of pain stimuli. We do all in our power to prevent and eliminate pain and distress in our laboratory animals.

Are the animals treated humanely?

Absolutely, yes. There are now incredibly rigorous standards that are required of institutions and individuals that engage in research with laboratory animals. As a result, in fact, laboratory animals at Palmer receive housing and care that is superior to most veterinary establishments and households. We meet and exceed very strict regulations regarding fresh air flow, temperature, lighting, noise, and humidity. Bedding, cages and food are strictly controlled and top quality. Our animal care facility is current state-of-the-art, and it is licensed by the U.S. Department of Agriculture and the State of Iowa. Personnel specially trained in laboratory animal care look after the animals. Palmer has adopted a “Code of Ethics for the Care and Use of Animals” that requires the prevention and alleviation of pain and suffering. If an animal appears ill or in distress, special procedures are initiated including obtaining consultation and care from a veterinarian specializing in laboratory animals.

What safeguards are in place to ensure that our laboratory animals are well treated? How do we know that Palmer complies with regulations and ethical norms

Current federal and state regulations regarding care of animals in research settings are strictly observed, along with even more rigorous standards from federal oversight organizations such as the Office of Laboratory Welfare of the U.S. National Institutes of Health. After a rigorous application process, Palmer was granted Assurance Number A4388-01 from the Office of Laboratory Animal Welfare. The U.S. Department of Agriculture (USDA) also separately reviews and licenses laboratory facilities after on-site inspections, which come randomly and without warning to the institution. Palmer recently passed just such an annual inspection. Another important local level of review and compliance is the Institutional Animal Care and Use Committee (IACUC). This committee is independent of the Palmer Chiropractic University System and has broad authority not only to approve the use of animals in any research projects at any of the Palmer colleges, but also to provide regulatory oversight of all animal care, to (randomly) inspect animal care facilities, to ensure that all animals are obtained from the best, most reputable suppliers, to require regular reporting during any research project involving animals and to stop any project at any time they feel optimal animal care is compromised. The IACUC consists of not less than five members, including a Doctor of Veterinary Medicine, non-Palmer-affiliated public members including a clergyman, a member whose primary concerns are in a nonscientific area and a practicing scientist. The veterinarian member must have training or experience in laboratory animal science and medicine. The committee includes a biologist who can provide members with an understanding of the nature and impact of proposed investigations as well as the housing and care of the species to be studied. All members receive special training and orientation regarding the responsibilities of committee membership. Reports on animal care and use issues must be filed at least twice per year with the Federal government after approval by the IACUC.

Where do you obtain laboratory animals?

Laboratory animals are purchased from federally licensed Class “A” suppliers. Class “A” animal breeders are in the business of providing healthy laboratory animals in a strictly controlled fashion. Palmer does not engage in animal husbandry, nor do we purchase any animals from animal shelters or pounds. In other words, there is no risk that someone’s lost pet would end up in any of Palmer’s research.

Can you really extrapolate research on quadrupeds to bipeds (i.e. humans)?

Yes, especially when dealing with questions about basic cellular and physiological functions. As genome research progresses, we are learning just how striking those similarities are. In terms of mammalian physiology, there is way more in common among species than differences. When it comes to studying the biomechanical and neural functions related to chiropractic subluxation and adjustment, we need to use animal models to validate and advance our understanding of the theory. The major difference between laboratory animals and humans in our research is size. This can be handled by scaling experimental values proportionally. Much of what we know about the immune system has come from studies with mice, while the last two decades of advances in the prevention and treatment of heart disease has come from studies with dogs. In fact, virtually every major health care advance in our understanding of pathology in the past century has come at least partly from animal studies.

Some say Palmer is doing this just to make money in grants. Is that true?

No. There are easier ways to make money. Engaging in research that requires the use of laboratory animals is hugely challenging in terms of expertise, infrastructure and expense, and grants help cover only part of the cost. So of course Palmer researchers apply for grants; otherwise, cutting-edge chiropractic research could not be done. But the assertion that we do this only for money is ridiculous. Grants are an incredibly difficult means of obtaining money. On average, only one in four grant applications is successful. Palmer invested over $4,000,000 for a renovated research facility, some of which is devoted to basic research studies. It will be a long time before that plus the annual $2.2 million of the research budget is reimbursed by grants. Regardless, we steadfastly believe that this is a small price to pay to scientifically validate chiropractic.

References

Brennan PC, Cramer GD, Kirstukas SJ, Cullum ME. Basic science research in chiropractic: The state of the art and recommendations for a research agenda. J Manipulative and Physiol Ther 1997;20:150-68.

Cleveland III CS. Researching the Subluxation on the Domestic Rabbit: A Pilot Research Program Conducted at the Cleveland Chiropractic College, Kansas City, MO. Scientific Review of Chiropractic 1965;1(8):1-23.

Cramer GD, Fournier Henderson CNR, Wolcott CC. Degenerative Changes Following Spinal Fixation in a Small Animal Model. J Manipulative and Physiolog Ther 2003; In press.

Cramer G et al. Zygapophysial joint changes following spinal fixation. Proceedings of the 2000 International Conference on Spinal Manipulation. Minnesota: 2000. p. 85-87.

DeBoer KF, Gastrointestinal myoelectric activity in rabbits with vertebral lesions: Preliminary report. Eur J Chiropractic 1984;32:131-42.

DeBoer KF, McKnight ME. Surgical model of a chronic subluxation in rabbits. J Manipulative Physiological Ther 1988;11(5):366-72.

DeBoer KF, Schutz M, McKnight ME. Acute effects of spinal manipulation on gastrointestinal myoelectric activity in conscious rabbits. Manual Medicine 1988;3:85-94.

Gatterman MI (ed): Foundations of Chiropractic: Subluxation. St. Louis: Mosby, 1995. (See Chapter 3, by Vernon.)

Henderson CNR, Cramer GD, Zhang Q. Development of a reversible small animal model of the chiropractic subluxation. Fifth World Federation of Chiropractic Congress. Auckland, New Zealand: 1999. p. 140-41.

Henderson CNR, DeVocht J, Kirstukas SJ, Cramer GD. In vivo biomechanical assessment of a small animal model of the vertebral subluxation. Proceedings of the 2000 International Conference on Spinal Manipulation. Minnesota: 2000 p. 193-5.

Kang, Y.M., Wheeler, J.D., Pickar, J.G. Stimulation of chemosensitive afferents from multifidus muscle does not sensitize multifidus muscle spindles to vertebral loads in the lumbar spine of the cat. Spine 2001; 26(14):1528-1536.

Kang, Y.M., Choi, W.S., Pickar, J.G. Electrophysiological evidence for an intersegmental reflex pathway in lumbar paraspinal tissues. Spine 2002; 27:3, E56.

Kang, Y.-M., Kenney, M.J., Spratt, K.F., Pickar, J.G. Somatosympathetic reflexes from the low back in the anesthetized cat. Journal of Neurophysiology 2003; (in press).

Lin HL, Fujii A, Rebechini-Zasadny H, Hartz DL. Experimental Induction of Vertebral Subluxation in Laboratory Animals. J Manipulative and Physiolog Ther 1978;1(1):63-6.

Pickar, J.G. An in vivo preparation for investigating neural responses to controlled loading of a lumbar vertebra. Journal of Neuroscience Methods 2000; 89:87-96.

Pickar, J.G. and Wheeler, J.D. Response of muscle proprioceptors to spinal manipulative-like loads in the anesthetized cat. Journal of Manipulative and Physiological Therapeutics 2000;. 24(1):2-11.

Pickar, J.G. Healthcare in the 21st Century --.Neurophysiologic issues of the subluxation lesion. Topics in Clinical Chiropractic 2001; 8(1):9-15.

Pickar, J.G. and Kang, Y.M. Short-lasting stretch of lumbar paraspinal muscles decreases muscle spindle sensitivity to subsequent muscle stretch. Journal of the Neuromusculoskeletal System 2001; 9(3):88-96

Pickar, J.G. Neurophysiological effects of spinal manipulation The Spine Journal 2001; 2:357-371.

Sung, P.S., Kang, Y.-M., Pickar, J.G. Effect of spinal manipulation speed on low
threshold mechanoreceptors in lumbar paraspinal muscles: a preliminary report. Spine
2003; (Submitted)

U.S. Congress. Office of Technology Assessment, Alternatives to Animal Use in Research, Testing, and Education. (Washington DC: US Government Printing Office, OTA-BA-273).

U.S. Department of Agriculture Animal Care Report, 2000. http://aphis.usda.gov

Wall Street Journal, August 1, 2002. “In the Headlights: As Man and Beast Clash on Highways, Both Sides Lose.” Page A1.

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