J Manipulative Physiol Ther. 2008 (Jun); 31 (5): 332–337 ~ FULL TEXT
César Fernández-de-las-Peñas, PT, PhD, Cristina Alonso-Blanco, PT,
Joshua A. Cleland, PT, PhD, Cleofás Rodríguez-Blanco, PT, DO,
Francisco Alburquerque-Sendín, PT, DO
Department of Physical Therapy,
Occupational Therapy, Physical Medicine and Rehabilitation,
Universidad Rey Juan Carlos,
OBJECTIVE: This study examines if C7–T1 manipulation results in changes in pressure pain thresholds (PPT) over bilateral C5–C6 zygapophyseal joints in asymptomatic subjects.
METHODS: Thirty subjects, 13 men and 17 women, without a current history of neck, shoulder, or upper extremity pain participated. Participants were randomly divided into 3 groups: experimental dominant group, subjects who received the manipulative thrust directed at the right side of the C7–T1 joint; experimental nondominant group, those who received the thrust on the left side of the C7–T1 joint; and a placebo group, those who received a sham-manual procedure. The outcome measure was the PPT on both right and left C5–C5 zygapophyseal joints, which was assessed at preintervention and 5 minutes postintervention by an assessor blinded to the treatment allocation of the subject. A 3–way repeated measures analysis of covariance was used to evaluate changes in PPT.
RESULTS: The analysis of covariance revealed time x group (F = 32.3; P < .001), time x side (F = 4.9; P < .05), time x sex (F = 7.93; P < .01), and time x group x sex (F = 7.606; P < .001) interactions. Post hoc analyses found that (a) both experimental groups showed greater improvements in PPT than the placebo group (P < .05), without significant differences between them (P > .6); (b) the right side had greater increases in PPT in both experimental groups (P < .05), but not within the placebo group (P > .8); (c) men experienced greater increases in PPT levels than women, particularly in the experimental nondominant group (P < .01). Within-group effect sizes were large for both experimental groups (d > 1), but small for the placebo condition (d < 0.2).
CONCLUSIONS: These results suggest that a C7–T1 manipulation induced changes in PPT in both right and left C5–C6 zygapophyseal joints in healthy subjects.
Key Indexing Terms: Pain Threshold, Manipulation, Spinal, Manipulation, Orthopedic
From the Full-Text Article:
The effectiveness of manual therapy techniques directed at the cervical spine in patients with neck pain or cervicogenic headache has been supported by an increasing number of high-quality randomized clinical trials [1–3] and systematic reviews. [4, 5] However, the potential risks associated with upper cervical spine manipulations have limited the use of techniques in physical therapy practice. Recent evidence has begun to suggest that spinal manipulation directed at the thoracic region may have potential therapeutic benefits with significantly lower chances of a detrimental side effect. [6–8]
Recent studies have found that thoracic spine manipulation results in immediate improvements in symptoms and function in patients with neck pain. [6–8] In addition, a specific subgroup of patients with neck pain who respond rapidly and dramatically to thoracic spine thrust manipulation has been identified.  It should be recognized that the aforementioned studies solely investigated the effects of thoracic manipulation on overall reports of pain and function. Although many possible explanations may exist to explain the physiologic rationale for improvements in this patient group, the true effects of cervicothoracic manipulation remain to be elucidated.
Because of the biomechanical relationship between the cervical and thoracic spine, perhaps disturbances in joint mobility in the cervicothoracic junction may serve as an underlying contributor to the development of neck disorders. [10–12] Further, it has been shown that mobilization/manipulation of joints remote to the patient' pain results in an immediate hypoalgesic effect. [13–15] For these reasons, it has been suggested that perhaps the incorporation of the cervicothoracic junction manipulation interventions could be also effective for the treatment of neck pain disorders. 
The neurophysiologic mechanisms by which spinal manipulative procedures are effective remain to be fully elucidated, and both segmental and central mechanisms have been proposed. It has been suggested that spinal manipulation may induce a reflex inhibition of pain or a reflex muscle relaxation by stimulation of joint mechanoreceptors.  Other suggested mechanisms have been the activation of the endogenous opiate system, [18, 19] the alteration of chemical mediators,  or possible activation of segmental inhibitory pathways.  Finally, some authors are claiming that joint mobilization procedures activate descending pain inhibitory systems. [22, 23]
A review of the literature found few studies exploring changes in mechanical pain sensitivity provoked by cervical manipulative procedures.  Vernon et al  found that cervical manipulation produces significantly greater increases in pressure pain thresholds (PPT; mechanical hypoalgesia) of tender points surrounding a cervical dysfunction. To further elucidate the physiologic mechanisms associated with spinal manipulative techniques, it is essential to determine the response in asymptomatic individuals who do not have any active central sensitization.  In fact, recently, Fernández-de-las-Peñas et al  have found that a cervical manipulation also resulted in mechanical hypoalgesia in both lateral elbows in a cohort of healthy subjects. However, the ability of cervicothoracic thrust manipulation to result in hypoalgesia over cervical spine segments has not been investigated. Hence, the purpose of this study was to examine if cervicothoracic thrust manipulation resulted in changes in PPT in the cervical spine in asymptomatic subjects.
The results of this clinical trial showed that cervicothoracic manipulation resulted in an increase in PPT in the cervical region, particularly C5–C6 zygapophyseal joints. These findings are similar to other studies that have shown that manual therapy techniques result in immediate improvements in PPT levels. [13–15, 25] In addition, the effect size for the groups that received C7–T1 manipulation was large, suggesting a clinically important increase in PPT after intervention.
Previous studies found that a hypoalgesic effect accompanied spinal mobilizations to a magnitude that was also statistically significant when compared with placebo or control groups. [13–15] Vicenzino et al  in a double-blind placebo-controlled, repeated measures study investigated the effects of cervical mobilizations (Maitland et al,  grade III lateral glides) on PPT and skin conductance in the limbs of subjects with lateral epicondylalgia. The results showed not only a statistically significant increase in sympatho-excitatory response and hypoalgesia but also a strong correlation (r = 0.82, P = .05) between the hypoalgesic effect and sympatho-excitatory response produced with spinal mobilization.  Sterling et al  showed that a posterior-anterior mobilization technique applied to the posterior joint of the C5–C6 spinal level resulted in an immediate increase of 25% in PPT on the symptomatic cervical level in patients with idiopathic neck pain. Fernandez-de-las-Peñas et al  showed that a single cervical manipulation resulted in mechanical hypoalgesia in bilateral lateral elbow regions. Although the proposed physiologic mechanism by which manual therapy produces its effects is not completely understood, it has been purported that manual therapy stimulates central control mechanisms (periaqueductal gray area). [22, 23] This is speculated to occur through the stimulation of descending inhibitory mechanisms. 
Although the thrust manipulation techniques were directed at the C7–T1 segments, it is likely that the manipulative procedure had a direct impact on the segments superior and inferior to the target vertebrae. A recent in vivo dynamic magnetic resonance imaging study investigated spinal kinematics during posteroanterior mobilization in the cervical spine.  Lee et al  investigated the effects of a grade III  mobilization directed at the C5 spinous process and found that the maximum intervertebral rotation occurred in the direction of extension at the C2–C3 segment (approximately 3.8°), whereas the C7–T1 segment actually rotated into flexion (approximately 2°).  This suggests that not only is a posterior-anterior mobilization directed at C5 not specific but also that the 2 to 3 segments above and below the target vertebrae experienced the greatest amount of rotation in the sagittal plane. Based on these data, it is likely that segments above and below C7–T1 junction also experienced a direct impact of the technique.
It is well documented that zygapophyseal joints are highly innervated and contain numerous mechanoreceptors. [37–39] Spinal manipulation may stimulate these mechanoreceptors resulting in alterations in sensory inputs. It has been speculated that spinal manipulation may alter aberrant sensory inputs produced by mechanoreceptors located within the innervated tissues of a zygapophyseal joint.  In other words, it is possible that spinal manipulation targeted at C7–T1 also impacted segments C5–C6 and assisted with the reduction of noxious stimuli that had previously been stimulating mechanoreceptors.
It is interesting to note that, in our study, thrust techniques directed at the side of the subject's dominant upper extremity had greater reductions in PPT. A recent study showed that a technique directed at C5–C6 on the side of the patients' dominant arm resulted in a significant increase in PPT over bilateral lateral elbow regions.  In addition, this same study did not identify a difference in the change in PPT among sexes. However, in the current study, men exhibited a greater improvement in PPT as compared with women. The reason why men experienced a greater improvement than women after C7–T1 manipulative intervention requires further investigation.
Finally, clinicians suggest that the C7–T1 area undergoes considerable postural stress in the modern-day computer-driven lifestyle, which may be related to the presence of joint restriction in this region. [10–12] It is possible that a number of participants had clinical evidence of C7–T1 restriction, which could also explain why the manipulation lowered the PPT. Future studies investigating the presence of segmental tenderness or joint restriction in the C7–T1 should be conducted.
Our study has several limitations. It should be recognized that we only assessed immediate effects of C7–T1 junction manipulation on pressure pain sensitivity. Futures studies should investigate the long-term impact of this technique on PPT levels. Another limitation is the fact that we used an asymptomatic sample. Hence, we do not know if the same effects would have occurred in patients with acute pain or in a state of central sensitization. Examining the effects of C7–T1 thrust manipulation on PPT in patient populations with neck pain, particularly whiplash, should be pursued. Third, joint cavitation bias can also have occurred because subjects in both experimental groups were not blinded to the joint cavitation. It is possible that joint cavitation may create an expectative or a placebo effect. However, this situation is so difficult, if not impossible, to control in a spinal manipulation study. Nevertheless, because our participants were unblinded from the manipulative cavitation, our results should be considered with caution. Finally, Ylinen et al  have recently suggested that although the repeatability of PPT assessment allows the use of algometry for research purposes, because of considerable variations on individual level, caution is advised when interpreting the results in clinical practice.
The application of a cervicothoracic junction manipulation induced changes in PPT in both right and left C5–C6 zygapophyseal joints in healthy subjects. In addition, the effect size for the groups that received C7–T1 manipulation was large, suggesting a clinically important increase in PPT after intervention. Different therapeutic mechanisms, either biomechanical or neurophysiologic, can be involved at the same time.
The application of a cervicothoracic junction manipulation evokes bilateral changes
in PPT over both C5–C6 zygapophyseal joints in healthy subjects.
Effect sizes in the manipulative group were large, suggesting a strong clinical
effect, whereas the effect size of the sham-manual group was small.
Different therapeutic mechanisms, either biomechanical or neurophysiologic,
can be involved at the same time.