Discussion

A.   Anatomical Research

The topic of anatomical research will be divided into studies that relate specifically to SM (“Studies Related to SM”) and those that add detail to the understanding of the spine (“Studies Adding to the Knowledge Base of the Spine”).

Biomechanics

Biomechanics is the study of the effects of loads applied to biologic cells, tissues or systems. Biomechanics has its origins from Galileo's studies of mechanics in general and his creation of the term mechanics as a subtitle of his book "Two New Sciences" (1638) to refer to force, displacement, and strength of materials. Arguably, the “father of biomechanics” is Giovanni Alfonso Borelli, who published in "De Motu Animalium" (1681) the principles of muscle movements based on statics and dynamics. However, the word “biology” and its concept as the study of living organisms did not occur until 1802 when the German naturalist, Gottfried Reinhold Treviranus, published his first volume "Biologie; oder die Philosophie der lebenden Natur". To rigorously understand SM and its effects requires an understanding of the principles of biomechanics.


A.   Manipulation Forces

Since the publication of the first white paper in 1997, there have been several important studies that have further clarified the loads that are applied during SM, and especially during high-velocity, low-amplitude (HVLA) SM. Triano and Shultz [150] measured the total force that was transmitted through the body during a side-lying lumbar or lumbosacral HVLA SM. The transmitted forces were similar to the applied forces for their temporal history, but the transmitted forces and moments were shown to vary substantially based on patient positioning. Herzog et al [151] measured the force distribution during thoracic HVLA SM and concluded that there was an important distinction between the total and effective applied forces, with the latter being much smaller than the total applied force. They found that the total peak force was being applied over a mean contact area of 34.8 cm², but for the thoracic spine, the physiologic contact area of the transverse processes was only 0.25 cm² (less than 1/100 of the total contact region). Hence, most of the total peak force was being applied to soft tissues (eg, skin, muscle, and fat), and only a small portion (~5 N) was being applied to the transverse process. A similar finding was reported by Kirstukas and Backman, [152] who reported that the “intense contact area” was on the order of 10 cm² during thoracic HVLA SM. Clearly, the effective applied force during HVLA SM in general will vary based on the contact area of the manipulator's hand and the aspect of the vertebra, but in general, the effective force will be less, and sometimes substantially so, than the applied force.

The 3-dimensional force applied during HVLA SM of the cervical, thoracic, and sacroiliac regions has now been measured. [153] The 3-dimensional data showed that forces in plane with the back (ie, Fx and Fy or shearing forces) always occurred during the SM, which was dominated by the normal (ie, Fz or perpendicular) applied force. The shearing forces were considerable in magnitude, ranging from a low mean of 15% (at T4–5) to a high of 29% (at sacroiliac) of the peak Fz force. As has been previously reported by others, [154] there was a consistent drop in the preload force magnitude just before the impulse portion of the HVLA SM, which is speculated to be due to a “countermovement” affect.

The role of sex in developing force magnitude has been investigated. [155] The only previous report that compared male and female manipulators found no significant differences during HVLA SM using a patient simulator. [156] Forand et al [155] used an experienced matched group (range, 1–24.5 year of experience) of female and male chiropractors (14 per group) and found that there were no significant differences between sexes in thoracic HVLA SM forces. The one exception was that, in the lower thoracic spine, men applied significantly greater preload than did women.

Another type of SM is mobilization or low-velocity low-amplitude SM, which is commonly used by physical therapists as well as other health professionals, including chiropractors. The general approach is to apply an increasing force over 5 to 10 seconds to determine the “end feel,” and then so calibrated, to apply a slow oscillation (~1 Hz for 10 seconds) about a mean graded force (I-IV arbitrary scale), which is less than the end feel. [157] Using an instrumented mobilization table, it was found that there was considerable variation in the force magnitudes used by experienced therapists for end feel, as well as grades I-IV mobilizations of L3 vertebra in healthy subjects. [157] When comparing treatment of younger vs older healthy subjects, it was found that, although mean forces were similar, smaller amplitudes and higher frequency of oscillations were used with older patients. [158] In a study of patients with nonspecific low back pain, there was considerable variation in the magnitudes of forces used, but the variation was strongly influenced not by the patient's severity of complaint but by the physical therapist's training. [159]

Somatic Nervous System

Knowledge of and research directions for understanding the effects of chiropractic spinal adjusting on the somatic nervous system needs, as its basis, an understanding of neurophysiology as it relates to structure and function of the vertebral column. Thus, 2 areas are presented in this portion of the white paper. The first area beginning immediately below represents a substantial portion of our knowledge base for understanding the neurophysiologic properties of paraspinal tissues. The second area beginning with the section on Effects of SMs on Muscle and Muscle Spindles reviews how neural elements of the vertebral column and their organization are affected by SM. Information is included that predates the 1997 white paper when it was not included in that article.

A.   Experimental Models to Study Somatic Inputs from the Paraspinal Tissues

Since publication of the original white paper, 2 experimental animal models have been developed that facilitate study of the relationship between spinal biomechanics and neurophysiology in general and of SM specifically: a cervical spine model developed by Bolton and Holland [211] and a lumbar spine model developed by Pickar. [212] Additional animal models also relevant to chiropractic spinal adjusting are presented in the section on Animal Models later in this paper. The experimental preparations enable application of controlled mechanical loads to individual vertebra and, at the same time, provide access to the dorsal roots for recording neural activity from paraspinal tissues affected by the mechanical load. The discharge properties of primary afferents with receptive fields in paraspinal tissues and the effects of these sensory inputs on somatomotor, somatovisceral, and central neural processing can be determined. The preparations use a servo-driven motor to control the displacement of or force applied to the spinous process.

Recently, a large animal model (goat) has been used to determine how strains in the facet capsule affect neural input from the capsule. [213] This model needs additional work to determine whether the capsule is sufficiently preloaded to enable accurate determination of strain and to confirm that identified neurons can be distinguished in the multiunit recordings.

The preparations described in this section provide the opportunity to conduct neurophysiologic studies not possible in humans. With information obtained from these animal models, hypotheses can be formulated and then tested noninvasively in humans.

Animal Models

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).


A.   Subluxation Mimic Models

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.

2. Specific basic science research topics.
   
   Animal research faculty should conduct studies to describe the nature and effects of spine lesions that respond to chiropractic manipulation and should also examine the specific attributes of the various SM methods and their differential effects.
   
   Rationale
   
   Observations from subluxation mimic and subluxation component models suggest the reality of the subluxation as an experimental phenomenon, but the existence of this spine lesion in the “real world” outside the laboratory has not been established in either animals or humans. Animal studies have been both informative and provocative, but their small number is presently inadequate as an evidence base for the chiropractic profession.
   
   The current body of animal research also suggests that stimulating spinal and paraspinal tissues produces significant somatic and visceral effects that may be uniquely different from those observed after stimulation of appendicular structures. This is encouraging and consistent with chiropractic theory, but many questions remain unanswered. Future animal studies should examine behavioral consequences of spine subluxation and manipulation as well as diverse anatomical and physiologic outcomes. These additional studies may provide a mechanistic explanation for field practitioner observations that both somatic and visceral problems improve with SM. [328]
   
   Research history strongly supports the value of animal studies as a window into the biologic mechanisms common to both animals and humans. It is clear that the development and use of animal models for chiropractic basic science research will play a central role in achieving recognition and respect for chiropractic by the world community. Moreover, this powerful tool will help to develop chiropractic theory, inform educators, and enhance the effectiveness of chiropractic practice.
   
   
   Action Steps

   1. The biomechanical spine lesion

      1. Identify and characterize putative biomechanical spine lesions that respond to spinal manipulative therapy (prevalence, causation, and biologic significance: nature, longevity, magnitude and diversity of effects, and natural history).
         

      2. Evaluate the deterministic role of specific segmental level and multiple involved segments on the biologic effect of these spine lesions.
         

      3. Evaluate the potential adverse contributory effect of biomechanical spine lesions on specific health conditions (using animal models with genetic predispositions to illnesses that mimic those of humans; such as asthma, cancer, diabetes mellitus, and hypertension).
         

      4. Determine to what degree homologues of the experimentally induced biomechanical spine lesions (subluxation mimics) exist in unmodified animals.

   2. Spinal manipulation

      1. Identify and characterize the effects of SM (biologic significance: nature, duration, and magnitude of effects).
         

      2. Evaluate the differential impact of SM application parameters such as rate (impulse duration), impulse frequency (single vs multiple impulse cycles), load vector (direction and magnitude of applied load), displacement vector (direction and magnitude of displacement), site of application (vertebral or paravertebral), and course of treatment (frequency and distribution of treatments over a treatment period).
         

      3. Evaluate the potential benefits of SM on specific health conditions commonly seen in chiropractic practice (using animal models that mimic specific human illnesses).
         

      4. Evaluate therapeutic benefits derived from SM to determine whether they are dependent on correcting a specific spinal lesion (eg, subluxation) or may be independent of a preexisting spine lesion.

   3. Global animal research issues

      1. Evaluate the possible deterministic role of bipedal vs quadruped posture on outcomes associated with biomechanical spine lesions and SM.
         

      2. Perform integrated animal and human studies that will examine specific biologic effects that have been shown in animal studies and will determine their homology in humans.

Immune Function Studies

Chiropractic field practitioners assert that SM produces improvement in several visceral conditions, including some that are thought to involve perturbed immune function. [332–334] Although chiropractic theory suggests that immunologic effects might be expected through neurologically mediated mechanisms, [335] few studies have addressed this topic. [317, 329, 336] Most of the evidence has been drawn from basic science studies that gave broad mechanistic support but did not specifically examine SM and its effect on immune function.

The central nervous system and immune system share modulator and receptor mechanisms by which the 2 systems communicate. Their interaction maintains both basal and stress-related homeostasis through 2 major pathways: the systemic sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. The homeostatic role of catecholamines released via the SNS is well known as a major regulator of metabolism, heart rate, blood pressure, and core temperature. [337] Similarly, the HPA axis has immunosuppressive and anti-inflammatory effects via release of adrenal glucocorticoids. [337] Within the past 2 decades, numerous studies have also shown direct SNS innervation of both primary and secondary lymphoid tissues in all species studied. [338] In these tissues, varicose sympathetic terminals form plexuses that run adjacent to vascular smooth muscle and also terminate in parenchymal lymphoid tissue well removed from blood vessels. These findings suggest that the SNS has a nonsynaptic noraderenergic, modulatory influence on lymphoid tissues. In addition, immune cells have been shown to express adrenoreceptors, which modulate lymphocyte trafficking, proliferation, receptor expression, and cytokine production. Cytokines are the hormone-like messenger molecules that immune cells use to integrate the functional activity of other immune cells. [339]

Consequently, the immune system is now thought to be “tuned” by contrasting neural influences; the local release of norepinephrine from nonsynaptic, postganglionic sympathetic terminals and circulating epinephrine secreted by the adrenal medulla. When internal or external influences disturb homeostasis, both the SNS and HPA axis are activated, thereby increasing the peripheral levels of catecholamines and glucocorticoids to restore the steady state of the internal milieu. In the 1930s, Selye [340] identified this integrated response as the general adaptation syndrome. Centrally, the 2 principal components of the general adaptation syndrome are the release of corticotropin-releasing hormone and the locus ceruleus–NE/autonomic (sympathetic) nervous system. These 2 systems participate in a positive, reverberating feedback loop in which activation of 1 system tends to activate the other as well. [341] Activation of the locus ceruleus–NE system leads to release of NE from an extraordinarily dense network of neurons throughout the brain. The functional consequence is increased arousal and vigilance, increased epinephrine release from the adrenal medulla, and increased peripheral sympathetic activity resulting in the release of NE from the varicose sympathetic nerve terminals. Norepinephrine and epinephrine bind to β2-adrenoreceptors on antigen-presenting cells and helper T cells, thereby inhibiting the production of TH1, proinflammatory cytokines (eg, interleukin 2, TNF-a, and interferon-?), while stimulating the production of TH2, anti-inflammatory cytokines (eg, interleukin 4, 5, and 10, and transforming growth factor–β). This shift in cytokine profiles from TH1 to TH2 produces a functional immune shift from a cellular response to a humoral response. Catecholamines may also increase regional immune responses by inducing interleukin 1, TNF-a, and interleukin 8 production. Therefore, sympathetic innervation may serve to localize and focus an inflammatory response via neutrophil accumulation and activation of specific humoral responses while systemically inhibiting TH1 cellular immunity responses. This would also protect the organism from the production of proinflammatory cytokines and other products of activated macrophages.

There is also considerable peptidergic influence contributed by small afferents that are confined mainly to the parenchyma of all lymphoid organs (eg, substance P, neurokinin A, and calcitonin gene-related peptide) and neuropeptides that are colocalized in the large dense-cored noradrenergic vesicles of sympathetic varicosities (eg, substance P, somatostatin, and vasoactive intestinal peptide). [338, 342] A close spatial relationship has been reported between peptidergic nerve fibers and mast cells, T cells, and macrophages in lymphoid tissues. [342] It is noteworthy that mast cells express receptors for substance P that trigger release of histamine and other factors such as leukotrienes. [343] Both substance P and histamine induce plasma extravasation and vasodilation in local tissues. In addition, substance P stimulates postganglionic sympathetic terminals to release norepinephrine and prostaglandins E2 and I2. [344] Consequently, in addition to their direct immunomodulatory effects on immune cells, neuropeptides can exert important indirect immunomodulatory effects via modulation of histamine release from mast cells and postganglionic sympathetic terminals in the parenchyma of lymphoid organs.

Finally, cytokines and their receptors have been shown within the central nervous system. Therefore, catecholamines and neuropeptides can regulate immune function, and cytokines can act as neuromodulators. The cytokines TNF-a, interleukin 1, and interleukin 6 have all been shown to modulate the SNS and the HPA axis. [345, 346]


A.   Immune Function and Subluxation/Spinal Manipulative Therapy

In the previous basic science white paper, [1] a review of the literature found relatively few studies that reported immune function effects associated with chiropractic manipulation or spine subluxation. Vernon et al [347] reported a slight, but statistically significant, increase in β-endorphin levels in asymptomatic males after cervical manipulation, whereas Sanders et al [348] and Christian et al [349] found no change in β-endorphin levels in either symptomatic or asymptomatic male study participants after chiropractic manipulation. Christian et al also reported no change in adrenocorticotropic hormone and cortisol levels between sham and treated groups or between pre- and post-treatment in any group. They concluded that changing β-endorphin levels did not mediate the analgesic response attributed to chiropractic manipulation, and that manipulation did not activate the HPA axis. [349] The work of Brennan et al [350–357] remains the only extended line of investigation into the effect of chiropractic SM and immune function. They reported that a single manipulation in the thoracic or lumbar spine produced a short-term priming of the polymorphonuclear cell response to an in vitro particulate challenge. They observed an enhanced chemiluminescent respiratory burst in both asymptomatic and symptomatic study participants. [350, 352, 357] This enhanced polymorphonuclear cell activity was associated with slight, but statistically significant, rise in plasma substance P. Further investigation suggested that this systemic effect was dependent on both the applied force and vertebral level. [352, 357] Brennan et al also found that patients presenting with neuromusculoskeletal complaints had reduced numbers of circulating natural killer cells; but these cells were not functionally impaired. [353–355] Lastly, SM did not alter the absolute or relative number of circulating immune cells (eg, B cells, T cells, and natural killer cells) in study participants enrolled in a clinical trial of SM for the treatment of chronic low back pain. [353]

An article published shortly after the 1997 basic science white paper reported a case series on 9 study participants of an initial 18 participants enrolled in the study. [358] Each study participant received 4 HVLA manipulation treatments to correct hypomobile vertebral segments over a 2–week treatment period. Saliva was collected for cortisol assay 2 weeks before the treatment period, during the 2–week treatment period, and 1 week after treatment. This was a very small study with poor participant compliance (50%). The study author reported no statistically significant effect of chiropractic manipulation on salivary cortisol levels, unless 1 outlier was removed from the data analysis. The very small sample, poor participant compliance, post hoc analysis, and several design weaknesses (no control, unclear attention to time of day for saliva collection, and possible confounding influences due to female estrogen cycle) make these results equivocal.

A subsequent salivary cortisol study by Whelan et al [359] examined 30 asymptomatic male chiropractic students in a randomized, 3–arm clinical trial (manipulation, sham, and no treatment control) to determine the effect of HVLA cervical manipulation on salivary cortisol secretion. These investigators were interested in determining whether chiropractic manipulation is itself a physiologic stressor capable of producing a significant stress response in asymptomatic subjects. They found no effect of chiropractic manipulation and concluded that, in asymptomatic subjects familiar with chiropractic manipulation, neither the “set-up” sham nor cervical manipulation induce a state of anxiety sufficient to disrupt the homeostatic mechanisms and activate the HPA axis. Unfortunately, the conclusions of this study can not be readily assessed because the authors did not discuss the statistical power of the study and failed to provide data for the reader to determine whether the study group size was adequate for detecting a clinically significant difference in salivary cortisol levels.

Two very recent articles, an animal study [330] and a human study [360] have reported interesting immune system responses after SM.

Song et al [330] produced a rat model of acute IVF inflammation with associated behavioral hyperalgesia, electrophysiologic changes, and neurohistologic pathology by injecting 30 µL of an “inflammatory soup” (bradykinin, serotonin, histamine, and prostaglandin) directly into the L5–L6 IVF of each of 100 experimental group rats. An additional 48 control rats underwent an equivalent surgical preparation but without injection of the inflammatory soup.

These investigators evaluated the therapeutic effects of 2 weeks of SM therapy (SMT) applied to the L4, L5, L6, or L5 and L6 spinous processes using an Activator II instrument (Activator Methods International). Behavioral hyperalgesia was evaluated before and periodically after IVF injection by recording foot withdrawal latencies to thermal stimuli and thresholds to mechanical indentation with von Frey filaments. They also recorded resting membrane potential, action potential current threshold, and repetitive discharge characteristics, in vitro, from neurons in the L5 dorsal root ganglion. Lastly, L5 DRG were taken from rats at different periods, stained with hematoxylin and eosin, and observed via light microscopy for signs of inflammation (eg, increased vascularization and satellitosis).

Song et al [330] reported that Activator SMT applied to L5, L6, or L5 and L6, but not L4, significantly reduced the severity and duration of both the thermal and mechanical hyperalgesia produced by IVF inflammation. Their electrophysiologic studies showed that inflammation-induced hyperexcitability of dorsal root ganglion neurons was also significantly reduced by the SMT. Finally, the increased vascularization and satellitosis observed in inflamed L5 dorsal root ganglion were significantly reduced 2 to 3 weeks after the Activator SMT. They concluded that Activator SMT can significantly reduce the severity and shorten the duration of pain and hyperalgesia caused by lumbar IVF inflammation. They also noted that the SMT effects were segment-specific.

The very recent article by Teodorczyk-Injeyan et al [360] reports that SMT in asymptomatic subjects down-regulates production of the inflammatory cytokines TNF-a and interleukin 1β (IL-1β). They also determined that this change in cytokine production was unrelated to serum substance P levels.

These investigators recruited 64 age- and sex-matched asymptomatic subjects who had not received an SM for a minimum of 6 months. Subjects were equally and randomly distributed across 3 study groups: SMT, sham-SMT, and venipuncture control. SMT subjects each received a single bilateral hypothenar (Carver-Bridge type) thrust applied to an upper thoracic (T1–T6) segment that had been previously identified as having a motion restriction. The SMT was judged to be successful if an audible release (cavitation) was heard. By contrast, the sham-SMT subjects received a similar setup and thrust that was directed such that no audible release was heard. Subjects in the venipuncture control group were treated similarly to the SMT and sham-SMT groups, except that no thrust was given. Blood samples were obtained from all subjects before any intervention (or sham intervention) and at 20 minutes and 2 hours after intervention (or sham intervention). All blood samples were coded to blind laboratory investigators to study group assignment.

Whole-blood cultures were subsequently activated with lipolysaccharide for 24 hours, and TNF-a and IL-1β production was determined from culture supernatants by specific immunoassays. Substance P production was determined from intact sera using a competitive immunoassay.

A statistically significant proportion of sham-SMT and venipuncture control subjects showed progressive increases in the synthesis of TNF-a and IL-1β, whereas a comparable proportion of SMT subjects showed a gradual decline in both cytokines. Subjects in all groups had normal baseline cytokine values within 2 hours after the intervention (or sham intervention). In all study groups, serum levels of substance P remained unaltered from baseline values.

Conclusion

The literature summaries of the 6 topic sections (anatomy, biomechanics, somatic nervous system, animal models, immune system, and human studies related to the autonomic nervous system) indicated that a significant body of basic science research evaluating chiropractic spinal adjusting has been completed and published since the 1997 basic science white paper. Much more basic science research in these fields needs to be accomplished, and the recommendations at the end of each topic section should help researchers, funding agencies, and other decision makers develop specific research priorities.

References