Spinal Manipulation Reduces Pain and Hyperalgesia After
Lumbar Intervertebral Foramen Inflammation in the Rat

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:

FROM:   J Manipulative Physiol Ther. 2006 (Jan); 29 (1): 5–13 ~ FULL TEXT

Xue-Jun Song, MD, PhD, Qiang Gan, MS, Jun-Li Cao, MD,
Zheng-Bei Wang, MD, Ronald L. Rupert, DC, MS

Department of Neurobiology,
Parker College Research Institute,
Dallas, TX 75229, USA.

OBJECTIVE:   To document potential mediating effects of the Activator-assisted spinal manipulative therapy (ASMT) on pain and hyperalgesia after acute intervertebral foramen (IVF) inflammation.

METHODS:   The IVF inflammation was mimicked by in vivo delivery of inflammatory soup directly into the L5 IVF in adult male Sprague-Dawley rats. Thermal hyperalgesia and mechanical allodynia were determined by the shortened latency of foot withdrawal to radiant heat and von Frey filament stimulation to the hind paw, respectively. Intracellular recordings were obtained in vitro from L5 dorsal root ganglion (DRG) somata. DRG inflammation was examined by observation of the appearance and hematoxylin and eosin staining. ASMT was applied to the spinous process of L4, L5, and L6. A series of 10 adjustments were initiated 24 hours after surgery and subsequently applied daily for 7 consecutive days and every other day during the second week.

RESULTS:   (1) ASMT applied on L5, L6, or L5 and L6 spinous process significantly reduced the severity and duration of thermal and mechanical hyperalgesia produced by the IVF inflammation. However, ASMT applied on L4 did not affect the response in rats with IVF inflammation or the controls; (2) electrophysiological studies showed that hyperexcitability of the DRG neurons produced by IVF inflammation was significantly reduced by ASMT; (3) pathological studies showed that manifestations of the DRG inflammation, such as the increased vascularization and satellitosis, were significantly reduced 2 to 3 weeks after ASMT.

CONCLUSIONS:   These studies show that Activator-assisted spinal manipulative therapy (ASMT) can significantly reduce the severity and shorten the duration of pain and hyperalgesia caused by lumbar IVF inflammation. This effect may result from ASMT-induced faster elimination of the inflammation and recovery of excitability of the inflamed DRG neurons by improving blood and nutrition supplement to the DRG within the affected IVF. Manipulation of a specific spinal segment may play an important role in optimizing recovery from lesions involving IVF inflammation.

Key Indexing Terms:   Spinal Manipulation, Hyperalgesia, Inflammation

From the FULL TEXT Article:


Lumbar intervertebral foramen (IVF) inflammation appears to play a critical role in the pathogenesis of low back pain. [1–3] This process can produce injury or disease to the structures and tissues within and/or adjacent to the IVF. [4–10] After inflammation or nerve injury or dorsal root ganglion (DRG) compression, the chemical factors such as cytokines, nerve growth factors, inflammatory mediators, and other substances release and activate and/or change the properties of DRG neurons and spinal dorsal horn neurons and contribute to hyperalgesia. [4, 5, 7, 11–15] Nerve-injured or DRG-compressed sensory neurons, in vitro, exhibit enhanced responses to inflammatory mediators. [4] To further understand the mechanisms of low back pain due to IVF inflammation, we have recently developed an animal model of IVF inflammation produced by in vivo delivery of inflammatory mediators directly into the IVF at L5. [16, 17] Rats with L5 IVF inflammation exhibit measurable pain and hyperalgesia and the primary sensory neurons become more excitable.

The mechanisms for the clinical effects of spinal manipulative therapy (SMT) are poorly understood but are thought to be related to mechanical, neurophysiological, and reflexogenic processes. [18, 19] In addition to traditional manual SMT, instruments such as the Activator Adjusting Instrument (AAI) have also been used to produce spinal mobilization. [20] The AAI was developed to precisely control the speed, force, and direction of the adjustive thrusts so that one may produce a safe, reliable, and controlled force to adjust osseous spinal structures. [21, 22] The AAI evolved in response to current knowledge in biomechanical and neurophysiological categories of investigation. Under the biomechanical model, issues such as tissue compliance (stiffness), response to input force (impedance), and natural frequency resonance of the spine were explored. In neurophysiological investigations, threshold frequencies and minimal forces required for stimulation of joint mechanoreceptors were investigated. [20, 23, 24]

The purpose of this study was to document potential mediating effects of SMT as performed using the AAI on pain and hyperalgesia produced by lumbar IVF inflammation in a small animal model with outcomes being assessed through behavioral, electrophysiological, and pathological approaches.


The present study investigated the effects of instrumented assisted SMT on pain and hyperalgesia produced by acute IVF inflammation in L5 in a small animal model by means of behavioral, electrophysiological, and pathological approaches. We found that the AAI-assisted SMT applied to the IVF inflamed spinous process can significantly reduce the severity and shorten the duration of pain and hyperalgesia, reduce the hyperexcitability of the DRG neurons, and alleviate inflammation of the DRG neurons after the IVF inflammation.

Inflammatory responses play key roles in behavioral hyperalgesia and hyperexcitability of DRG cells in inflammatory pain as well as in neuropathic pain. [7–11] Intervertebral foramen inflammation is one of the main reasons for low back pain. After IVF inflammation, the chemical factors such as cytokines, nerve growth factors, inflammatory mediators, and other substances release and activate and/or change the properties of DRG neurons and spinal dorsal horn neurons as well as increase their excitability and therefore contribute to pain and/or hyperalgesia. [4, 5, 7] In the present study, injection of the inflammatory mediators into the IVF directly produces acute inflammation to the constituents within the IVF, that is, DRG, nerve root, and blood and lymph vessels, and, furthermore, may produce ischemia and compromise the delivery of oxygen and nutrients. Interestingly, our studies show that ASMT can significantly alleviate the symptoms and shorten the duration of pain and hyperalgesia caused by the IVF inflammation. Furthermore, by means of electrophysiological and pathological assessments, our studies showed that the faster relief of pain and hyperalgesia after ASMT may result from the faster recovery of hyperexcitability of the sensory neurons and elimination of the DRG inflammation.

Although the mechanism of action of this intervention is unknown, there are numerous possibilities. It was found that the lumbar vertebrae experienced an axial displacement, posteroanterior shear displacement, and rotational displacement at the upper spinal segment levels. Coupled spinal motion was also detected in more than just the vertebra receiving a direct thrust. [20] In our present study, the AAI was applied to the small animal with IVF inflammation and produced significant treatment effects on the pain and hyperalgesia. Based on the findings of research on Activator adjustments on a human spine, the increased movement of the affected intervertebral joints (facets) and the coupled spinal motion may contribute to the treatment effect of Activator via improving the blood and nutrition supply to the DRG within the affected IVF.

In addition, chiropractic adjustments delivered by the AAI may “normalize” articular afferent input to the central nervous system with subsequent recovery of muscle tone, joint mobility, and sympathetic activity. [25, 26] It was also hypothesized that a chiropractic lumbar thrust would produce sufficient force to coactivate all of the mechanically sensitive receptor types, [27] and adjustments made with the AAI are thought to accomplish the same task. [28] An Activator adjustment may have the capacity to coactivate type III, high-threshold mechanoreceptors. Both types III and IV receptors in diarthrodial joints, as well as type II in paravertebral muscles and tendons, are responsive to vertebral displacement. [29] In addition, Activator adjustment may be effective by activating the receptors in the spinal cord and some of the ascending and descending signaling pathways that involve pain modulation. [30] These may contribute to the mechanisms underlying the treatment effects of the AAI.

The importance of specificity as it relates to which spinal segment or segments are manipulated has been a longstanding debate within the chiropractic profession. Most treatment techniques emphasize the importance of manipulation of a specific vertebral segment. [31] The general belief is that specific adjustments are therapeutically superior to general mobilization. Recent studies suggest several problems with specific chiropractic adjustments. First, chiropractors appear to be unable to accurately palpate and identify the spinal segment they often seek to target. [32] Secondly, due to the size of the contact points on the physician's hand, there is a question regarding the ability to deliver specific force to the specific area of the spine where it is intended. The present studies are important in addressing the issue of treatment specificity. However, through literature reviews, we could not locate evidence to support or refute that primary question of whether making contact on specific vertebrae is in fact important. This research is believed to be the first demonstration that reduced hyperalgesia from DRG inflammation was significant in animals where manipulation included the specific lumbar vertebrae and not in animals that were treated only at an adjacent vertebral segment. This study suggests that specificity was an important treatment variable in reducing hyperalgesia in this DRG inflammation model.


The present study shows that ASMT can significantly reduce the severity and shorten the duration of pain and hyperalgesia caused by lumbar IVF inflammation. This effect may result from the adjustment-induced faster elimination of the inflammation and recovery of excitability of the inflamed DRG neurons. The ASMT may produce more movement of the affected intervertebral joints (facets), which may improve blood and nutrition supply to the DRG within the affected IVF. Our study also suggests that treating a specific vertebral level may be an important variable in chiropractic practice.


The authors thank Dr Cheryl Hawk for her comments on the manuscript, Dr Charlotte Watts for her technical support, and Maria Dominguez for her assistance in laboratory management. The Activator was kindly provided by Dr Arlan W. Fuhr (Activator Methods International).


  1. Devor, M.
    The pathophysiology of damaged peripheral nerves.
    in: PD Wall, R Melzack (Eds.) Text book of pain. 3rd ed.
    Churchill Livingstone, Edinburgh; 1994: 79–100

  2. Sen, O, Aydin, MV, Bagdatoglu, C, Ertorer, ME,
    Bolat, FA, Yalcin, O et al.
    Can E-selectin be a reliable marker of inflammation in lumbar disc disease?.
    Neurosurg Rev. 2005; 28: 214–217

  3. Brisby, H, Olmarker, K, Larsson, K, Nutu, M, and Rydevik, B.
    Proinflammatory cytokines in cerebrospinal fluid and serum in patients
    with disc herniation and sciatica.
    Eur Spine J. 2002; 11: 62–66

  4. Song, XJ, Zhang, JM, Hu, SJ, and LaMotte, RH.
    Somata of nerve-injured neurons exhibit enhanced responses
    to inflammatory mediators.
    Pain. 2003; 104: 701–709

  5. Song, XJ, Xu, DS, Vizcarra, C, and Rupert, RL.
    Onset and recovery of hyperalgesia and hyperexcitability of sensory neurons
    following intervertebral foramen volume reduction and restoration.
    J Manipulative Physiol Ther. 2003; 26: 426–436

  6. Ji, RR and Woolf, CJ.
    Neuronal plasticity and signal transduction in nociceptive neurons:
    implications for the initiation and maintenance of pathological pain.
    Neurobiol Dis. 2001; 8: 1–10

  7. Neumann, S, Doubell, TP, Leslie, T, and Woolf, CJ.
    Inflammatory pain hypersensitivity mediated by phenotypic switch in
    myelinated primary sensory neurons.
    Nature. 1996; 384: 360–364

  8. Lu, X and Richardson, PM.
    Responses of macrophages in rat dorsal root ganglia
    following peripheral nerve injury.
    J Neurocytol. 1993; 22: 334–341

  9. Cui, JG, Holmin, S, Mathiesen, T, Meyerson, BA, and Linderoth, B.
    Possible role of inflammatory mediators in tactile hypersensitivity
    in rat models of mononeuropathy.
    Pain. 2000; 88: 239–248

  10. Leach, RA.
    Vertebral subluxation complex hypothesis.
    in: RA Leach (Ed.) The chiropractic theories:
    principles and clinical applications. 3rd ed.
    Williams & Wilkins, Baltimore; 1994: 201–230

  11. Wagner, R and Myers, RR.
    Endoneurial injection of TNF-alpha produces neuropathic pain behaviors.
    Neuroreport. 1996; 7: 103–111

  12. Waxman, SG, Kocsis, JD, and Black, JA.
    Type III sodium channel mRNA is expressed in embryonic but not adult
    spinal sensory neurons, and is reexpressed following axotomy.
    J Neurophysiol. 1994; 72: 466–470

  13. Song, XJ, Hu, SJ, Greenquist, K, and LaMotte, RH.
    Mechanical and thermal cutaneous hyperalgesia and ectopic neuronal
    discharge in rats with chronically compressed dorsal root ganglia.
    J Neurophysiol. 1999; 82: 3347–3358

  14. Song, XJ, Vizcarra, C, Xu, DS, Rupert, RL, and Wong, ZN.
    Hyperalgesia and neural excitability following injuries to the
    peripheral and central branches of axon and somata of dorsal root ganglion neurons.
    J Neurophysiol. 2003; 89: 2185–2193

  15. Song, XJ, Wang, ZB, Gan, Q, and Walters, ET.
    cAMP and cGMP contribute to sensory neuron hyperexcitability and hyperalgesia
    in rats with dorsal root ganglia compression.
    J Neurophysiol. 2005; 95: 479–492

  16. Song, XJ, Gan, Q, Wang, ZB, and Rupert, RL.
    Hyperalgesia and hyperexcitability of sensory neurons induced by local
    application of inflammatory mediators: an animal model of acute lumbar
    intervertebral foramen inflammation.
    in: Proceedings (Abstract Viewer/Itinerary Planner) of the 34th Annual Meeting
    of the Society for Neuroscience; 2004 Nov;
    San Diego, CA. Society for Neuroscience,
    Washington, DC; 2004: 30

  17. Song, XJ, Gan, Q, Wang, ZB, and Rupert, RL.
    Lumbar intervertebral foramen inflammation–induced hyperalgesia and
    hyperexcitability of sensory neurons in the rat. ([abstract])
    FASEB J. 2004; 1616

  18. Bronfort, G, Haas, M, and Evans, R.
    The clinical effectiveness of spinal manipulation for musculoskeletal conditions.
    in: S Haldeman (Ed.) Principles and practice of chiropractic. 3rd ed.
    McGraw Hill, New York; 2005: 147–165

  19. Vernon, H.
    The treatment of headache, neurologic, and non-musculoskeletal
    disorders by spinal manipulation.
    in: S Haldeman (Ed.) Principles and practice of chiropractic. 3rd ed.
    McGraw Hill, New York; 2005: 167–182

  20. Fuhr, AW and Menke, JM.
    Activator methods chiropractic technique.
    Top Clin Chiropr. 2002; 9: 30–43

  21. Richard, DR.
    The activator story: development of a new concept in chiropractic.
    Chiropr J Aust. 1994; 24: 28–32

  22. Osterbauer, P, Fuhr, AW, and Keller, TS.
    Description and analysis of activator methods chiropractic technique.
    in: DJ Lawrence (Ed.) Advances in chiropractic.
    Mosby, St. Louis; 1995: 471–520

  23. Fuhr, AW and Smith, DB.
    Accuracy of piezoelectric accelerometers measuring displacement of a
    spinal adjusting instrument.
    J Manipulative Physiol Ther. 1986; 9: 15–21

  24. Smith, DB, Fuhr, AW, and Davis, BP.
    Skin accelerometer displacement and relative bone movement of adjacent
    vertebrae in response to chiropractic percussion thrusts.
    J Manipulative Physiol Ther. 1989; 12: 26–37

  25. Keller, TS.
    In vivo transient vibration assessment of the normal human thoracolumbar spine.
    J Manipulative Physiol Ther. 2000; 23: 521–530

  26. Henderson, CNR.
    Three neurophysiological theories on the chiropractic subluxation.
    in: MI Gatterman (Ed.) Foundation of chiropractic: subluxation.
    Mosby, St. Louis; 1995: 225–233

  27. Gillette, RG.
    A speculative argument for the coactivation of diverse somatic receptor
    populations by forceful chiropractic adjustments.
    Man Med. 1987; 3: 1–14

  28. Nathan, M and Keller, TS.
    Measurement and analysis of the in vivo posteroanterior impulse response
    of the human thoracolumbar spine: a feasibility study.
    J Manipulative Physiol Ther. 1994; 17: 431–441

  29. Brodeur, R.
    The audible release associated with joint manipulation.
    J Manipulative Physiol Ther. 1995; 18: 155–164

  30. Song, XJ and Rupert, RL.
    The central projections of spinal receptors.
    in: S Haldeman (Ed.) Principles and practice of chiropractic. 3rd ed.
    McGraw Hill, New York; 2005: 269–288

  31. Cooperstein, R, Gleberzon, BJ, and Mootz, RD.
    in: Technique systems in chiropractic.
    Churchill Livingstone, New York; 2004: 155–171

  32. Perle, SM.
    The illusion of specificity.
    J Am Chiropr Assoc. 2002; 39: 30–31


Since 2-26-2016

                  © 1995–2024 ~ The Chiropractic Resource Organization ~ All Rights Reserved