J Orthop Sports Phys Ther. 2007 (Jun); 37 (6): 325–329 ~ FULL TEXT
CéSar Fernández-De-Las-Peñas, PT, PhD, Marta Pérez-De-Heredia, OT,
Miguel Brea-Rivero, OT, Juan C. Miangolarra-Page, MD, PhD
Department of Physical Therapy,
Physical Medicine and Rehabilitation,
Universidad Rey Juan Carlos,
DESIGN: A placebo, control, repeated-measures, single-blinded randomized study.
OBJECTIVES: To compare the immediate effects on pressure pain threshold (PPT) tested over the lateral elbow region following a single cervical high-velocity low-amplitude (HVLA) thrust manipulation, a sham-manual application (placebo), or a control condition; and to analyze if a different effect was evident on the side ipsilateral to, compared to the side contralateral to, the intervention.
BACKGROUND: Previous studies investigating the effects of spinal manual therapy used passive mobilization procedures. There is a lack of studies exploring the effect of cervical manipulative interventions.
METHODS: Fifteen asymptomatic volunteers (7 male, 8 female; aged 19–25 years) participated in this study. Each subject attended 3 experimental sessions on 3 separate days, at least 48 hours apart. At each session, subjects received either the manipulation, placebo, or control intervention provided by an experienced therapist. The manipulative intervention was directed at the posterior joint of the C5–6 vertebral level. PPT over the lateral epicondyle of both elbows was assessed preintervention and 5 minutes postintervention by an examiner blinded to the treatment allocation of the subject. A 3–way analysis of covariance (ANCOVA) with intervention, side, and time as factors, and gender as covariate, was used to evaluate changes in PPT.
RESULTS: The analysis of variance detected a significant effect for intervention (F = 31.46, P < .001) and for time (F = 33.81, P < .001), but not for side (F = 0.303, P > .5). A significant interaction between intervention and time (F = 15.74, P < .001) was also found. Gender did not influence the comparative analysis (F = 0.252, P > .6). Post hoc analysis revealed that the application of a HVLA thrust manipulation produced a greater increase of PPT in both elbows, as compared to placebo or control interventions (P < .001). No significant changes in PPT levels were found after the placebo and control interventions (P > .6). Within-group effect sizes were large for PPT levels in both elbows after the manipulative procedure (d > 1.0), but small after placebo or control intervention (d < 0.1).
CONCLUSIONS: The application of a manipulative intervention directed at the posterior joint of the C5–6 vertebral level produced an immediate increase in PPT over the lateral epicondyle of both elbows in healthy subjects. Effect sizes for the HVLA thrust manipulation were large, suggesting a strong effect of unknown clinical importance at this stage, whereas effect sizes for both placebo and control procedures were small, suggesting no significant effect.
From the FULL TEXT Article:
The Guide to Physical Therapist Practice  defines mobilization or manipulation as “manual therapy techniques comprising a continuum of skilled passive movements aimed to the joints and/or related soft tissues that are applied at different speeds and amplitudes.” Manipulation refers to techniques involving high-velocity low-amplitude (HVLA) thrusts, whereas mobilization refers to techniques performed as lower-velocity movements.  Spinal manipulative therapy is a commonly used intervention for the management of neck disorders. [9, 10] Previous studies have demonstrated that cervical manipulation increases active range of motion [4, 28] and decreases pain [15, 21] in patients with neck pain.
The neurophysiological mechanisms by which spinal manipulative therapy is effective remain to be fully elucidated, and both segmental and central mechanisms have been suggested. Spinal manipulation may induce a reflex inhibition of pain, or a reflex muscle relaxation by stimulation of joint capsule mechanoreceptors  or muscle spindles. [3, 27] Mechanical stimulus provoked by the manipulative procedure may also alter concentrations of inflammatory mediators  or trigger segmental inhibitory mechanisms.  Another suggested mechanism is through the activation of the endogenous opiate system. [10, 30]
It has been determined that manual mobilization procedures induce mechanical, but not thermal, hypoalgesic effects.  This manual therapy-induced hypoalgesia appears to be nonopioid in nature, because it is not reversed by the application of naloxone  and does not develop tolerance to repeated application of manual interventions.  Further, mechanical hypoalgesia provoked by manual procedures is concurrent with sympathetic nervous system [5, 32] or motor system  excitation. Based on data from a study conducted on animal joints, mobilization-induced analgesia involves serotonin and nor-adrenaline receptors in the spinal cord.  These findings support the hypothesis that manual procedures can stimulate descending inhibitory pain systems. [2, 24, 35]
Previous studies investigating hypoalgesic effects of spinal manual therapy have focused on passive mobilization techniques (eg, lateral glide of the cervical spine,  posterior-anterior joint mobilization,  or mobilization-withmovement [17, 33]). The authors are not aware of any studies that have explored hypoalgesic effects following cervical manipulative procedures. Therefore, the aims of the present study were to compare the immediate effects on pressure pain thresholds (PPT) over the lateral elbow region following a single cervical HVLA manipulation, a sham-manual intervention (placebo), or a control condition, and to analyze if a different effect was evident on the side ipsilateral to, compared to the side contralateral to, the intervention.
In this study we measured an immediate increase in PPT for both elbows following the application of a single cervical HVLA thrust manipulation in healthy subjects. The hypoalgesic effect occurred after the manipulative procedure, but not with a placebo or control intervention. Further, effect sizes for the manipulative group were large for both elbows, suggesting a strong effect, whereas effect sizes of placebo or control procedures were small.
Our results provide evidence that spinal manipulative therapy exerts a mechanical hypoalgesic effect. These findings are consistent with those of previous studies that have investigated the hypoalgesic effects evoked by manual mobilization of either spinal (ie, cervical region) or peripheral (ie, elbow) joints. Vicenzino et al  found that a lateral glide of the cervical spine produced an immediate increase of 25% in PPT in patients with lateral epicondylalgia. Sterling et al  demonstrated that a posterior-anterior mobilization technique applied to the posterior joint of the C5–6 spinal level resulted in an immediate increase of 25% in PPT on the symptomatic cervical level in patients with idiopathic neck pain. Other authors investigating the effects of mobilization-with-movement intervention of the elbow found an increase in PPT ranging from 10% to 20% in patients with lateral epicondylalgia. [17, 33] These findings provide evidence that manual therapy directed to the cervical spine or to the elbow joint exerts a mechanical hypoalgesic effect.
Possible mechanisms for mechanical hypoalgesic effects include both segmental and central inhibitory mechanisms. Local effects  could result from stimulation of large-diameter low-threshold mechanoreceptors at the spinal cord level,  according to the gate control theory.  Zusman  suggested that spinal manual procedures might produce a decrease in joint afferent activity. It may be that segmental stimulation elicited by manipulation directed at the posterior joint of the C5–6 vertebral level, which exerts a neural influence on the lateral epicondyle, can result in increased PPT.
Although these segmental mechanisms may be possible, they do not explain the effects produced distant to the treated site. Several studies have demonstrated that manual mobilization may produce an adequate stimulus to activate descending inhibitory pain systems. [17, 18, 23, 32, 33] In the present study, an increase in PPT was found in both elbows, supporting the activation of central structures, because a unilateral manipulative procedure produced a bilateral response. Nevertheless, there is insufficient evidence to claim a major role for either peripheral or central mechanisms.
Our study has several limitations. First, we only examined the short-term effects of spinal manipulative therapy directed at the cervical spine. The fact that immediate changes occurred after spinal manipulation provides impetus for future research in this area. Further studies are needed to examine long-term effects of spinal manipulative procedures. Second, it is possible that a joint-cracking or -popping sound during the HVLA thrust manipulation could have created a placebo effect on the subjects. Nevertheless, this situation is difficult, if not impossible, to control in a manipulation study. Thirdly, the present study was conducted on healthy subjects, so we cannot extrapolate the present findings to a patient population. It is necessary to repeat the same procedure in different patient populations that may benefit from cervical manipulation, such as those with neck pain, whiplash-associated disorders, cervicogenic headache, and lateral epicondylalgia.
The application of a manipulative intervention directed at the posterior joint of the C5–6 vertebral level produced an immediate increase in PPT for both elbows in healthy subjects. Effect sizes for the HVLA thrust manipulation were large, suggesting a strong effect of unknown clinical importance at this stage, whereas effect sizes for both placebo and control procedures were small, suggesting no significant effect.