New Research Project Demonstrates Relief Of Allodynia With Chiropractic Adjusting
SOURCE: J Manipulative Physiol Ther 2012 (Jan); 35 (1): 18-25
Jaqueline Trierweiler, Débora Negrini Göttert,
Günther Gehlen, PhD
Academic of Chiropractic from the University Feevale,
Laboratory of Comparative Histophysiology, ICS,
University Feevale, Novo Hamburgo, RS, Brazil.
OBJECTIVE: The purpose of this study was to evaluate the mechanical allodynia in animals after immobilization and chiropractic manipulation using the Activator instrument through the Von Frey test in an animal model that had its hind limb immobilized as a form to induce mechanical allodynia.
METHOD: Eighteen adult male Wistar rats were used and divided into 3 groups:
- control group (C) (n = 6) that was not immobilized;
- immobilized group (I) (n = 6) that had its right hind limb immobilized;
- immobilized and adjusted group (IAA) (n = 6) that had its right hind limb immobilized and received chiropractic manipulation after.
The mechanical allodynia was induced through the right hind limb immobilization. At the end of the immobilization period, the first Von Frey test was performed, and after that, 6 chiropractic manipulations on the tibial tubercle were made using the Activator instrument. After the manipulation period, Von Frey test was performed again.
RESULTS: It was observed that after the immobilization period, groups I and IAA had an exacerbation of mechanical allodynia when compared with group C (P < .001) and that after the manipulation, group IAA had a reversion of these values (P < .001), whereas group I kept a low pain threshold when compared with group C (P < .001).
CONCLUSION: This study demonstrates that immobilization during 4 weeks was sufficient to promote mechanical allodynia. Considering the chiropractic manipulation using the Activator instrument, it was observed that group IAA had decreased levels of mechanical allodynia, obtaining similar values to group C.
The present study investigated the effects of instrumented assisted spinal manipulation therapy on mechanical allodynia produced by the immobilization of the right hind limb in a small animal model through the Von Frey test. Our group observed that the immobilization of the right hind limb, for a period of 4 weeks, might produce an exacerbation of the local mechanical allodynia and that the manipulation applied to the tibial tubercle, using the Activator instrument, might reduce the severity of local allodynia induced by the immobilization.
Knee joint immobilization is a common medical practice used to manage musculoskeletal injuries. However, this may cause degenerative alterations in articular tissues and lead to progressive histologic changes in animals, including proliferation of connective and synovial tissues, fibrous adhesions at articular surfaces, cartilage erosion, and necrosis with subchondral bone alterations.  In addition, immobilization also appears to result in a reduction in mechanical strength of joint structural components, thereby leading to progressive degeneration. [37, 38] Most of these studies have analyzed the effect of joint immobilization on the articular tissues; however, little attention has been given to the study of the neuroanatomical  and neurophysiologic changes as the result of joint immobilization, as in this study.
The immobilization of the right hind limb was used in this study as the form of inducing nociception because studies proposed that limb immobilization leads to an increase in pain, [10, 11, 12, 13] sensibility, [10, 11] decrease range of motion, [12, 14] muscular atrophy, intraarticular adhesions [12, 14] and edema,  loss of bone mass and density,  reduction of strength and resistance to fatigue. 
In the present study, the immobilization device proposed showed to be effective because it produced a local allodynia and did not cause loss of weight, skin lesions, swelling, and inflammation, but some rats were able to remove the immobilization. It is suggested that the animals removed the immobilization because the immobilization model used in this study was only attached to the member with a plastic belt and Procitex tape. Studies showed that the immobilization models of rats’ hind limb that had a belt attached to the abdomen of the animals are safer and more effective, so preventing them from damaging the hind limb splint and from removing the immobilization. [18, 19]
A noxious stimulation to an intact tissue produces a physiologic pain that activates the protective withdrawal reflex aiming to prevent additional injuries. When it is continuous, the noxious stimulus produces a pathologic pain, which leads to inflammation or tissue injury. In this case, mechanisms of peripheral and central sensitization are generated, which involves the release of chemical mediators in the injured local as well as in central nervous system regions.  These sensory changes are observed as hyperalgesia and allodynia, in this study, measured using the Von Frey test that showed that, when compared with the control group C, rats that had their limb immobilized had an increase of the local mechanical allodynia.
The mechanisms for the clinical effects of chiropractic manipulation on pain are poorly understood, maybe because pain is strongly related to behavioral issues, so this evaluation becomes difficult. From this point, the discussion of our results was based on the Von Frey test, a method that determines tactile and mechanical nociceptive threshold [41, 42, 43] because the deformation of its filaments can be converted in strength parameters.  So, pain assessment is no longer subjective, and the information obtained in this study becomes relevant for the study of the physiologic mechanisms involved in chiropractic manipulation and pain.
In the second Von Frey test, performed after the period of 6 chiropractic manipulation using the Activator instrument, it was observed that the animals from group IAA had a significant reduction of local mechanical allodynia when compared with group I. This finding shows that the manipulation of the tibial tubercle using the Activator instrument may be effective in reducing local allodynia after 4 weeks of immobilization.
Analgesia induced by manipulation has been demonstrated in human and animal studies, using traditional spinal manipulative therapies and also instruments such as the Activator. Manipulation of cervical or thoracic spine produces an immediate, localized hypoalgesic effect and reduces pain in human subjects. [44, 45, 46, 47] It has been shown also that knee joint manipulation decreases secondary mechanical hyperalgesia in the paw induced by injection of capsaicin into the ankle joint in rats. 
In addition, it has been shown that spinal manipulation using the Activator equipment at the spinous processes of L5, L6, or L5 to L6, in an animal model of intervertebral foramen inflammation, reduced the severity and duration of thermal and mechanical hyperalgesia measured by the mechanical latency of withdrawal to radiant heat and Von Frey filaments, respectively. 
The spinal manipulation has been shown to be more effective in treating spine chronic pain that allopathic treatments and other forms of alternative treatments. [49, 50] In addition, in acute low back pain, the chiropractic treatment shows higher efficiency than muscle relaxants and is more effective than other treatments for neuropathic pain in individuals with some kind of neuromuscular disorder. 
Furthermore, it has been shown that cervical manipulation produces hypoalgesia in people with lateral epicondylitis or cervical spine pain and is accompanied by sympathoexcitation, evidenced by changes in skin conductance, blood flow, and/or skin temperature. [13, 52] This fact contributes significantly to the understanding of the manipulative therapy, in particular, the previously proposed mechanism of action that spinal manipulation leads to activation of descending inhibitory pain pathways from the periaqueductal gray matter,23, 24, 25 site where the opioid peptides, specially β-endorphin, play an important role on the pain-descending pathways, [53, 54] possibly by attenuating the spinal release of nociceptive mediators. 
A study found a small but significant increase in plasma β-endorphin levels 5 minutes after cervical spinal manipulation on healthy male subjects. This finding appears to indicate that, at least in healthy subjects, the manipulation might activate the endogenous antinociceptive system subserved by plasma β-endorphins. 
The β-endorphin is one of the most important opioids because it has a potent opioid activity and it is more resistant to enzymatic degradation, when compared with the enkephalins. [55, 56] In the periaqueductal gray matter, the analgesic effects of opioid peptides occur through their action on the suppression of inhibitory influences caused by neurotransmitters found in neurons that are part of the descending inhibitory pathways.  It has been demonstrated also that the β-endorphin participates on the induction of antinociception by moderating the nociception that accompanies tissue inflammation. 
The source of β-endorphin at the site of the injury seems to be T cells. In somatic inflammatory pain, the best characterized and clinically relevant are leukocyte-derived opioid peptides such as β-endorphin and enkephalins. Circulating opioid-producing immune cells accumulate in peripheral inflamed tissues where they secrete the opioids. The released opioid peptides activate opioid receptors on peripheral sensory neurons resulting in inhibition of inflammatory pain in animals and humans. 
Glia cells seem to have also an important role in pain, where the central nervous system glia cells become activated after damage to peripheral tissues or nerves, a factor that induces hyperexcitability in pain-signaling pathways and contributes to abnormal pain perception. When glia is activated, it releases proinflammatory substances, and neuronal excitability is enhanced, an outcome known to result in enhanced pain sensitivity and to reduce the effectiveness of opioid peptides. By the fact that activated glia releases a variety of neuroexcitatory substances that potentiate neurotransmission, especially proinflammatory cytokines, blocking glial activity may be a novel way of controlling pain. 
This study has provided the first documentation that chiropractic manipulation using the Activator on the tibial tubercle may reduce the severity of local mechanical allodynia caused by the immobilization of rats’ hind limb for a period of 4 weeks, through the Von Frey test. This analgesic effect of manipulation might occur from the activation of pain-descending inhibitory system through the release of chemical mediators from neurons located in the periaqueductal gray matter. We suggest that more studies should investigate the effects of manipulation in the central and peripheral pathways of pain control that induces antinociception, first in animal models and then in humans.