The remarkable scientific progress in both industry and medicine over the last 100 years has been responsible, in large part, to a transition from observational to experimental research. [305, 306] Human clinical studies contributed greatly to this progress, but animal studies have permitted investigators to perform experimental interventions that were not possible in human studies, and allowed a wider range of study designs. In addition, statistical power is easier to obtain in animal studies because large numbers of animals can be evaluated at relatively low costs, and animal study groups can be genetically homogeneous. Moreover, research animals are often bred to have genetic predispositions to illnesses that mimic those of humans, such as asthma, [307] cancer, [308] diabetes mellitus, [309] and hypertension. [310] These important features, and the ability to strictly control potentially confounding influences, make animal research an essential tool for today's health care researchers. Consequently, the need for animal models in chiropractic research has been acknowledged in each of the major reviews of scientific progress in chiropractic. [1, 311, 312]
Despite this, some still question how we can learn anything about people from studying animals. The basis for this concern lies in the obvious anatomical and physiologic differences between humans and animals. Animal studies are generally used to examine fundamental mechanisms that are common to both humans and nonhuman species. In addition, as noted above, many human diseases can be mimicked in animal models. Consequently, animal research provides information about fundamental mechanisms common to both humans and animals, and often suggests new hypotheses for evaluation in subsequent human studies. The discovery of insulin provides an excellent example. It was also one of the most dramatic events in the history of health care research. [313] Animal studies showed that the pancreas was a critical organ in the development of diabetes mellitus. Additional work produced an extract of the pancreas that reduced hyperglycemia and glycosuria in animals that had been previously rendered diabetic by removal of the pancreas. After further extensive evaluation with laboratory animals, the purified extract was deemed ready for human tests. In the first human trial, a 14-year-old boy with severe diabetes received an intramuscular injection of the “purified” pancreatic extract but failed to show clinical improvement and developed a sterile abscess at the injection site. [314] However, on the strength of the previous animal studies, work continued to further purify the pancreatic extract, and additional human studies were conducted. These new human studies, using the purified extract, showed a tremendous clinical improvement in all subjects. [314] Therefore, animal studies revealed the critical role of insulin in diabetes, provided a source of the hormone for subsequent study, and showed the potential of insulin as a therapeutic agent. All of these events were necessary before human clinical trials of insulin could begin. In 1923, the Nobel Prize for Physiology or Medicine was awarded to Banting and Macleod, recognizing that the discovery of insulin had [315] “conferred the greatest benefit on mankind.” The current era of chiropractic experimental research began after the first federally funded workshop to examine SM, The Research Status of Spinal Manipulative Therapy, in 1975. [311] At the conclusion of this historical conference, it was widely acknowledged that little basic or clinical research data were available to evaluate the claims of clinicians using SM.
Immediately after the first Research Agenda Conference in 1996, a white paper was published on the status of basic science research in chiropractic, "Basic Science Research in Chiropractic: The State of the Art and Recommendations for a Research Agenda". [1] A contemporary review by Vernon was cited in which 18 animal studies examined spine subluxation (1 historical monograph, 4 abstracts, and 13 articles). [316] A recent review by Henderson, Animal Models in the Study of Subluxation and Manipulation: 1964 to 2004, presents synopses of 34 animal studies (5 abstracts and 29 articles) published within the past 40 years. [317] In this review, studies were included if they specifically examined subluxation, the osteopathic lesion (somatic dysfunction), or SM. Studies examining subluxation or somatic dysfunction were grouped under the general term subluxation studies. These studies used animals to model either subluxation (31 studies) or SM (3 studies). The 31 subluxation studies examined either “full-mimic models” that attempted to induce spine fixation in intact animals (14 studies) or “component models” that emulated specific mechanical or chemical components attributed to spine subluxation (17 studies). The 3 SM studies used either manual (1 study) or instrumental interventions (2 studies).
Only 1 subluxation mimic model has been introduced since the 1996 Research Agenda Conference. This model, the external link model, combines surgically implanted spinous attachment units and an external link system to produce reversible, mechanical fixation of 3 adjacent lumbar segments (L4, L5, and L6) in the rat. [13] Cramer et al [13] used the external link model to examine degenerative changes after spine fixation. They observed stiffness and Z joint changes that developed within weeks after experimental fixation of a spine segment. Both the occurrence (number of involved segments) and severity (0–3 scale, least to most severe) of degenerative changes were recorded. These investigators reported significant differences in Z joint degeneration between fixed segments and nonfixed segments within the same animal. In addition, the occurrence and severity of articular degeneration and osteophyte formation on Z joints in rats with fixated vertebrae was significantly greater than similar degenerative changes, on comparable segments, in never-linked control rats.
This subluxation mimic study provided strong evidence that decreased vertebral motion (vertebral fixation) produced degenerative changes in the Z joint that were greater for longer periods of fixation. Generally, these degenerative changes continued to progress after removal of the fixating links. However, the data also suggested that time thresholds exist, before which removal of the experimental fixation (links) may spontaneously reduce or reverse the fixation-induced degenerative changes. These time thresholds appeared to be earlier for facet surface degeneration (occurring between 1 and 4 weeks of fixation time) and later for osteophytic degeneration (occurring between 4 and 8 weeks of fixation time). In addition, facet degeneration was observed to occur earlier than osteophyte formation. The existence of these time thresholds is intriguing, and may have clinical significance. However, the authors warned that there is no known basis for projecting rat time frames to human subjects. Further work with this model and subsequent human studies are required to expand our understanding of these issues.