Christopher J. Colloca, DC, Tony S. Keller, PhD, Robert Gunzburg, MD, Phd,
Katelijne Vandeputte, MD, Arlan W. Fuhr, DC
Postdoctoral and Related Professional Education Department Faculty,
Logan College of Chiropractic,
St. Louis, MO, USA.
BACKGROUND: Although the mechanisms of spinal manipulation are poorly understood, the clinical effects are thought to be related to mechanical, neurophysiologic, and reflexogenic processes. Animal studies have identified mechanosensitive afferents in animals, and clinical studies in human beings have measured neuromuscular responses to spinal manipulation. Few, if any, studies have identified the basic neurophysiologic mechanisms of spinal manipulation in human beings or animals.
OBJECTIVES: The purpose of this clinical investigation was to determine the feasibility of obtaining intraoperative neurophysiologic recordings and to quantify mixed-nerve root action potentials in response to lumbosacral spinal manipulation in a human subject undergoing lumbar spinal surgery.
METHODS: An L4-L5 laminectomy was performed in a 62-year-old man. Short-duration (<0.1 ms) mechanical force, manually assisted spinal manipulative thrusts (150 N) were delivered to the lumbosacral spine with an Activator II Adjusting Instrument. With the spine exposed, spinal manipulative thrusts were delivered internally to the L5 mammillary process, L5-S1 joint, and the sacral base with various force vectors. This protocol was repeated by contacting the skin overlying respective anatomic landmarks. Mixed-nerve root recordings were obtained from gas-sterilized platinum bipolar hooked electrodes attached to the S1 nerve root at the level of the dorsal root ganglion during the spinal manipulative thrusts and during a 30-second baseline period during which no spinal manipulative thrusts were applied.
RESULTS: During the active trials, mixed-nerve root action potentials were observed in response to both internal and external spinal manipulative thrusts. Differences in the amplitude and discharge frequency were noted in response to varying segmental contact points and force vectors, and similarities were noted for internally and externally applied spinal manipulative thrusts. Amplitudes of mixed-nerve root action potentials ranged from 200 to 2600 mV for internal thrusts and 800 to 3500 mV for external thrusts.
CONCLUSIONS: Monitoring mixed-nerve root discharges in response to spinal manipulative thrusts in vivo in human subjects undergoing lumbar surgery is feasible. Neurophysiologic responses appeared sensitive to the contact point and applied force vector of the spinal manipulative thrust. Further study of the neurophysiologic mechanisms of spinal manipulation in humans and animals is needed to more precisely identify the mechanisms and neural pathways involved.
From the Full-Text Article:
Musculoskeletal disorders including low back pain (LBP) present a tremendous burden to society. LBP is the second most frequent symptomatic reason for patient visits to primary care physicians, second only to the common cold.  The National Center for Health Statistics in the United States reported that 14.3% of new patient visits to physicians are for LBP symptoms, totalling 12,900,000 visits for chronic LBP and 4,114,000 visits for low back symptoms.  LBP is the leading cause of disability in people younger than age 45 and the second leading cause of industrial absenteeism.  LBP disables 2.4 million Americans at any given time, one half of whom are chronically disabled.  From 1984 to 1990, estimated direct costs of spinal disorders increased from $13 billion to $23 billion,  and combined with indirect costs, figures have estimated that LBP represents a cost of more than $50 billion annually to the United States. These statistics and similar international epidemiologic studies have demonstrated the enormous societal impact of spinal disorders. Back pain has been called a “20th century health care disaster.” 
Most health care for musculoskeletal disorders, including LBP, is provided for by conservative care.  Spinal manipulative therapy (SMT) is a conservative treatment that has been investigated for its effectiveness in the treatment of LBP in randomized controlled trials of patients with acute, sub-acute, and chronic LBP. [7-10] Estimates have indicated that approximately 96% of SMT is performed by chiropractors.  As federal and private sector funding for chiropractic services has increased in recent years, [11, 12] investigations into the proposed effectiveness and mechanisms of spinal manipulation have drawn attention.
Although the mechanisms of SMT remain poorly understood, the beneficial clinical effects of SMT are thought to be related to mechanical, neurophysiologic, and reflexogenic mechanisms.  Mechanical models have evolved with the theory that SMT produces realignment and improved function of misaligned and dysfunctional functional spinal units.  Recent evidence has demonstrated that significant functional spinal unit movements are produced by SMT in selected treatments applied to animal models [15, 16] and in human studies. [17, 18] Neurophysiologic models theorize that SMT may also stimulate or modulate the somatosensory system and subsequently may evoke neuromuscular reflexes. [13, 19-21] Such mechanical and neurophysiologic studies suggest that joint manipulation may have both direct and indirect clinical benefits.
Recognizing the enormous impact of LBP to health care, researchers have investigated the role of somatic structures as a source of LBP. In recent years, neurophysiologic and neuroanatomic investigations have been conducted to identify and characterize somatosensory units located within the tissues of the lumbar spine to clarify their role in LBP. Devices such as glass rods, metal probes, nylon threads, and electrical impulses have been used to mechanically stimulate somatic structures and afferent units. [22-25] Mechano-sensitive and nociceptive afferents have been identified in the lumbar intervertebral disks, [26-29] zygapophyseal joints, [25, 30-32] spinal ligaments, [22, 33-35] and the paraspinal musculature [36, 37] in both animal and human studies. This research and that of others  have identified these tissues as probable sources of LBP and somatic referred pain. [36, 39-41] Spinal nerve roots and dorsal root ganglia have also been shown to be the source of radicular pain. [42, 43] The beneficial effects of SMT have been thought to be associated with mechanosensitive afferent stimulation and presynaptic inhibition of nociceptive afferent transmission in the modulation of pain, [44, 45] inhibition of hypertonic muscles,  and improvement of functional ability. [11, 47, 48]
Although recent research has begun to investigate the electromyographic responses to spinal manipulation, [13, 49-52] little is known about the sources of reflexogenic stimulation derived from SMT. In addition, few investigations of the neurophysiologic and biomechanic effects of SMT have been performed to date. The purpose of this study, therefore, was to determine the feasibility of obtaining intraoperative spinal nerve root neurophysiologic recordings in response to SMT stimulation of somatic structures in a human subject undergoing lumbar spinal surgery. A second objective was to determine if a short-duration, mechanical stimulation delivered in lumbar SMT by the mechanical force, manually assisted means was associated with mixed nerve root responses in the S1 nerve root and if such responses depended on contact point and applied vector. To derive a testable model in which SMT could be investigated in human subjects, SMT was delivered internally by directly contacting vertebral segments and externally by contacting the skin overlying respective anatomic points.
Numerous publications have discussed different techniques of intraoperative spinal cord and nerve root recordings. [54-56] Intraoperative spinal cord monitoring with somatosensory-evoked potentials (SEPs) has been used to monitor nerve root decompression  and has become the standard of care for scoliosis surgery in the United States, reducing the incidence of postoperative myelopathy. [58, 59] Dermatomal SEPs have been found to be more sensitive than mixed-nerve SEPs for the detection of radiculopathy. However, dermatomal SEPs are of lower amplitude than mixed-nerve root potentials and require signal-averaging to yield reproducible data. Consequently, dermatomal SEPs are technically more difficult to perform in an operating room environment. [60-62] Monitoring of mixed-nerve root potentials from the lumbosacral nerve roots, however, provides a simple method for continuous assessment of real-time responses during mechanical stimulation and was deemed appropriate for our study.
Several technical challenges had to be addressed in preparing for this study, most notably the short time frame available for measurements. Because prolonged operation times have been associated with an increase in surgical complications (including increased blood loss, postoperative spinal infection, and ischemic optic neuropathy), [63, 64] collecting data in a timely manner from patients undergoing surgery becomes a significant challenge. As a result, patients are less willing to participate. For these reasons, the time allowed for experimental set-up and data collection was constrained to a minimum and therefore limited the number and type of experiments that could be performed.
The AAI II has been found to produce bone movement in in vivo animal and human studies. [15, 16, 18] Because other researchers have investigated neurophysiologic discharges after the applications of stresses and strains to the lumbar facet joints in animals, [20, 22, 24, 25, 28, 31, 65, 66]0 we sought to determine the feasibility of obtaining intraoperative spinal nerve root neurophysiologic recordings in response to mechanical stimulation of somatic structures by SMT. To our knowledge, this study is the first to report in vivo lumbosacral nerve root action potential responses to SMT in human beings. Although the method was found to be feasible, for future work we plan to use an AAI II equipped with a load cell and accelerometer to quantify the threshold for mechanical stimulation and the temporal relation of the nerve root potential and mechanical stimulus frequency.  In addition, further study is required to more carefully identify artifacts associated with spinal manipulative thrusts.
In our experiment, we did not account for the temporal relation between the spinal manipulative thrust and the action potential responses and the sensitivity of the bipolar recording electrodes to movement. For this reason, a separate experiment was conducted with the same protocol discussed herein. Before applying spinal manipulative thrusts to the subject, the electrode was purposefully slid by the surgeon along the S1 nerve root approximately 1 cm during a 2.5-second data recording period. No appreciable action potential discharges were observed, confirming that the electrodes are not considerably movement sensitive (Fig 13).
In this same experiment, SMT was next applied to the right L5 mamillary process with an anterior vector by an AAI II equipped with a load cell and accelerometer. Load and acceleration signals were analyzed during simultaneous S1 action potential recordings to provide the temporal relation between the spinal manipulative thrust and the nerve root discharge (Fig 14).
In assessing the time line relations between the onset of mechanical stimulation during SMT and the resultant neurophysiologic response (2 to 4 ms), our findings were consistent with other neurophysiologic discharges recorded in response to mechanical and electrical stimulation. [30, 31, 66]
The aforementioned research has focused on responses to SMT delivered by contacting the skin overlying respective anatomic points, including the reflex-sensitive musculature. We sought to examine the feasibility of measuring mixed-nerve action potential responses to SMT delivered internally and externally (on the skin). Because of the limitations of human subjects, we were not able to measure discharges of individual rootlets or afferent units as is commonly reported in animal models, and we were not able to electrically stimulate the nerve and calculate the respective conduction velocities of the units. Our measurements were obtained from the region laterally adjacent to the dorsal root ganglion of S1, and therefore we could obtain only mixed-nerve root action potential responses to SMT. Appreciation of the possible peripheral sensitization effects of underlying inflammation leads us to choose the asymptomatic S1 nerve root for our source of data collection as opposed to recording from L5 or L4 levels in this particular patient.
In this study, mixed-nerve action potentials were observed in association with both internal and external spinal manipulative thrusts delivered with the AAI II. Internal thrusts that contacted the L5 mammillary process and zygapophyseal joint during the active 30-second trial produced mixed-nerve root action potentials that were larger in magnitude when the force vector was anterior-superior compared with anterior only. Because the internally delivered spinal manipulative thrusts were not delivered to the overlying paraspinal musculature, the source of the mixed nerve-root discharge probably originated from discoligamentous mechanosensitive afferents in the posterior elements of the spine (intervertebral disk, zygapophyseal joint, and spinal ligaments) or from nerve root stimulation produced by bone movement. Preload of the zygapophyseal joint may also stimulate mechanosensitive afferents by stretching of the facet joint capsule. The actual sources of the action potentials, however, are not readily discernible. For unresponsive spinal manipulative thrusts, poor electrode contact or accumulation of fluid in the area of the electrodes may have caused the results. Another consideration may have been a simple failure to stimulate the nerve root from the thrusts.
The apparent directional sensitivity of mixed-nerve action potential discharge demonstrated by the larger magnitude responses during the anterior-superior-vectored thrusts on the zygapophyseal joint may be caused by increased stretching of the joint capsule associated with this force vector. Because of the anatomic positioning of the zygapophyseal joints, it stands to reason that an anterior-superior-vectored force will cause the maximum deformation during a posteroanterior thrust. Consequently, this may evoke a greater mechanoreceptive response by stimulating underlying afferent units. A similar response from afferent discharges from the lumbar facet joints was also reported in animal studies when forces were applied in different directions and magnitudes. [20, 24, 25, 31] Ideally, action potential measurements should be performed while simultaneously measuring translations and rotations of functional spinal units during the application of SMT force vectors. This is considered an essential element for future research.
Another example of the directional sensitivity of the mixed-nerve root response was demonstrated by thrusts applied to the sacral base, where the smallest amplitude discharge responses were observed. The reduced response may reflect that the sacral base is a stiff, anatomic connection of the sacrum with its articulating pelvis. Thrusts applied to the sacral base may not create stretching of the lumbar facet joint to the same extent as thrusts applied to L5. If this is the case, a decreased mechanosensitive afferent response would be expected. Of further interest are the similarities of mixed-nerve root responses in comparing thrusts delivered internally with those delivered externally by contacting the skin overlying the respective anatomic points. Because the applied vector was found to be associated with mixed-nerve root discharge amplitude, it appears that the line of drive (force vector) of the AAI II may be important in providing stretch of the lumbar facet joint (Fig 15).
Because the segmental contact point for the externally applied thrusts was on the skin overlying the underlying anatomical landmarks, it is likely that the mechanosensitive afferent response may originate in the skin, muscle, and discoligamentous tissues. Of interest to the chiropractic profession is the apparent specificity of the chiropractic adjustment. As shown in previous animal models and as is apparent in our study, distractive and compressive loads have resulted in differing neurophysiologic responses. If therapy is to be effective, the directional sensitivity of mechanosensitive afferents provides a rationale for the need for appropriate education and training of the practitioner who applies SMT. This may have important implications for chiropractic education and the legislative efforts concerning the abilities of untrained individuals attempting to embark on spinal manipulation as an intervention within their scope of practice.
The beneficial effects of spinal manipulation have been thought to be associated with mechanosensitive afferent stimulation and presynaptic inhibition of nociceptive afferent transmission in the modulation of pain. [44, 45] Our work has demonstrated that mixed-nerve root action potential responses are associated with SMT. However, we were not able to determine constituent components of fiber type. Because similar amplitude discharges were observed with the anterior-superior-vectored thrusts both internally and externally, we hypothesize that stimulation of mechanosensitive discoligamentous and muscular afferents may be responsible for the results. Further study is necessary to determine the underlying source of the mixed-nerve root signal. Such studies will most likely require an animal model because of the invasiveness of the dissection and stimulation required. We aim in future work to simultaneously monitor nerve roots and neuromuscular responses to compare temporally to the spinal manipulative thrust and bone movement. Future work should also include basic science investigations of the effect of SMT on inhibition of hypertonic muscles, together with biomechanic measures to assist in the clinical usefulness of this research.
As demonstrated by data obtained in this study, it is possible to record mixed-nerve action potentials in response to spinal manipulative thrusts in vivo in human subjects undergoing lumbar spinal surgery. The amplitude of mixed-nerve root action potentials was associated with the applied force vector of the SMT and segmental contact point. Further research is required to investigate the sources of nerve stimulation and the clinical relevance of these findings. Ultimately, such research may help to provide a greater understanding of the neurophysiologic mechanisms of spinal manipulation and to identify the mechanisms involved more precisely and will form the basis for further study in both human beings and animals.