FROM:
J Manipulative Physiol Ther. 2017 (Mar); 40 (3): 127–138 ~ FULL TEXT
Heidi Haavik, PhD, BSc (Chiro), Imran Khan Niazi, PhD,
Kelly Holt, PhD, BSc (Chiro), Bernadette Murphy, PhD, DC
Centre for Chiropractic,
New Zealand College of Chiropractic,
Mount Wellington,
Auckland, New Zealand.
Heidi.haavik@nzchiro.co.nz
OBJECTIVE: The purpose of this preliminary study was to assess whether the dual somatosensory evoked potential (SEP) technique is sensitive enough to measure changes in cortical intrinsic inhibitory interactions in patients with chronic neck or upper extremity pain and, if so, whether changes are associated with changes in pain scores.
METHODS: The dual peripheral nerve stimulation SEP ratio technique was used for 6 subjects with a history of chronic neck or upper limb pain. SEPs were recorded after left or right median and ulnar nerve stimulation at the wrist. SEP ratios were calculated for the N9, N13, P14-18, N20-P25, and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median and ulnar nerves. Outcome measures of SEP ratios and subjects' visual analog scale rating of pains were recorded at baseline, after a 2-week usual care control period, and after 12 weeks of multimodal chiropractic care (chiropractic spinal manipulation and 1 or more of the following: exercises, peripheral joint adjustments/manipulation, soft tissue therapy, and pain education).
RESULTS: A significant decrease in the median and ulnar to median plus ulnar ratio and the median and ulnar amplitude for the cortical P22-N30 SEP component was observed after 12 weeks of chiropractic care, with no changes after the control period. There was a significant decrease in visual analog scale scores (both for current pain and for pain last week).
CONCLUSION: The dual SEP ratio technique appears to be sensitive enough to measure changes in cortical intrinsic inhibitory interactions in patients with chronic neck pain. The observations in 6 subjects revealed that 12 weeks of chiropractic care improved suppression of SEPs evoked by dual upper limb nerve stimulation at the level of the motor cortex, premotor areas, and/or subcortical areas such as basal ganglia and/or thalamus. It is possible that these findings explain one of the mechanisms by which chiropractic care improves function and reduces pain for chronic pain patients.
KEYWORDS: Neuroplasticity; Sensory Gating; Somatosensory Evoked Potentials; Spinal Manipulation; Transcutaneous Nerve Stimulation
From the Full-Text Article:
Introduction
Spinal manipulation is known to result in clinical improvements in spinal function and reduction of both acute and chronic low back and neck pain. [1–7] However, the mechanism(s) responsible for the restoration of function and relief of pain after manipulative care are not well understood. We have yet to fully understand the neurophysiological mechanisms responsible for such clinical improvements after spinal manipulation of any kind. It is of interest to us whether chiropractic care can induce changes in various aspects of central nervous system (CNS) functioning, including alterations in reflex excitability, [8–12] sensory processing, [13] and motor control. [12]
A recent study used the dual somatosensory evoked potential (SEP) ratio technique to further explore these CNS alterations following chiropractic adjustment/manipulation. [14, 15] This experimental technique has previously been used by Tinazzi et al., [16] who found that dystonic subjects exhibited an abnormality in the intrinsic inhibitory interactions within the somatosensory system. The technique can be used to measure central integration of dual somatosensory input. [16] This can be achieved by comparing the amplitudes of SEP peaks obtained by stimulating the median and ulnar nerves simultaneously (MU) with the amplitude obtained from the arithmetic sum of the SEPs elicited by stimulating the same nerves separately (M + U). The ratio of MU to M + U indicates the central interaction between afferent inputs from these 2 peripheral nerves and, thus, reflects the degree to which the CNS filters or gates excessive somatosensory afferent information. [17–21]
Previous research has indicated that healthy individuals have smaller central MU SEP amplitudes (ie, SEP amplitudes following MU) compared with the M + U amplitudes (ie, SEP amplitude calculated as the arithmetic sum of the individual median and ulnar SEPs). [16, 22] However, in conditions such as dystonia16 and Huntington’s disease, [23] increased central SEP ratios have been observed. The increased SEP ratios suggest that these individuals receive distorted and excessive (ie, not spatially filtered) afferent input from their affected limb or limbs, which may potentially cause their motor system to transform these afferent inputs into abnormal “unhealthy” motor outputs. Sensorimotor disturbances are also known to persist beyond acute episodes of pain, [24, 25] and such sensorimotor disturbances are thought to play a defining role in the clinical picture and chronicity of different chronic pain conditions. [26] We therefore hypothesized that patients with chronic pain may also have increased central dual SEP ratios.
Our previous studies using the SEP ratio technique examined the effects of cervical spine chiropractic manipulation (also known as chiropractic adjustments) and a period of repetitive muscular contractions. [14, 22] This work demonstrated that the dual-peripheral-nerve-stimulation SEP technique may be used as a sensitive measure of sensorimotor integration (SMI). The experiment involved recording SEPs before and after the subjects performed a repetitive thumb abduction task for 20 minutes. The results suggest that the cortical system becomes less able to suppress the dual input after 20 minutes of repetitive thumb abduction. [22] These SEP changes were unrelated to peripheral factors, as the N9 responses remained stable. The N9 SEP peak reflects the afferent signal over the brachial plexus [27] before it enters the CNS, and thus can be used to ensure that the incoming signal is consistent before and after an intervention. Furthermore, these experiments demonstrated that the subjects’ N30 SEP peak ratios decreased significantly after a single chiropractic manipulation of the cervical spine. As the N30 SEP peak is thought to reflect early cortical SMI, [28] the authors argued that their results suggest that the subject’s SMI networks’ ability to suppress the dual input after the adjustment was increased. [14] The N30 SEP peak ratios remained decreased even after repeating the 20–minute repetitive thumb abduction task. This suggested that the treatment effects appear to have altered the way in which each subject’s CNS responded to the repetitive thumb typing task. [14]
Using dual somatosensory input and comparing the SEP ratios are more robust against the variations in placement of recording and stimulating electrodes that can affect SEP amplitudes when measuring SEP data evoked from stimulation of a single peripheral nerve. As it measures the degree of central surround-like inhibition of somatosensory input, it is less affected by the recording and stimulating setup, thus allowing more reliable measures over time and enabling us to compare across subjects. Thus, it may be a useful tool to measure long-term central neurophysiological changes that may occur with chiropractic care.
The purpose of this preliminary study was to assess whether the dual SEP technique is sensitive enough to measure changes in cortical intrinsic inhibitory interactions in patients with chronic neck pain after a 12–week period of chiropractic care and, if so, whether any such changes related to changes in symptomatology.
Discussion
The major finding in this preliminary study was that after 12 weeks of chiropractic care in a small sample of chronic pain patients, there was evidence of improved suppression of SEPs evoked by dual-upper-limb nerve stimulation at the cortical level of the lemniscal pathway. More specifically, the improved suppression of dual input was evident for the frontal P22–N30 SEP component. Alongside this change in the N30 SEP ratio, the subjects reported a decrease in both current pain and average pain over the last week. A control period of 2 weeks of no intervention resulted in no significant changes in any SEP peak ratio.
Frontal P22–N30 SEP Peak Changes
The changes observed in the current study occurred only for the frontal N30 component of the SEP peaks. Although some authors have suggested this peak is generated in the postcentral cortical regions (ie, S1), [46, 47] the majority of the evidence suggests that this peak is related to a complex cortical and subcortical loop linking the basal ganglia, thalamus, premotor areas, and primary motor cortex. [48–52] The frontal N30 peak is therefore thought to reflect SMI. [28] The decreased frontal N30 SEP peak ratio observed in the current study therefore suggests that an increase in surround inhibition or filtering of sensory information from the upper limb may be occurring somewhere in these cortical and subcortical loops linking the basal ganglia, thalamus, premotor areas, and primary motor cortex after 12 weeks of chiropractic care. The SEP ratio change after the chiropractic intervention appears to be caused by an increased inhibition of the dual peripheral input, as the N30 MU data were also significantly decreased. Impaired surround inhibition prior to the period of chiropractic care may account for this finding, and may be an important central neural dysfunction present in chronic pain populations. This should be investigated further. The effect size of the changes in N30 MU amp (0.61) and MU to M + U ratio (0.66) are considered to be moderate and can be used to inform future research. [53]
No changes in MU, M + U, or MU to M + U ratios were observed after the 2–week control period. The results after chiropractic care are therefore unlikely a result of time alone. However, the design of our study cannot prove it was the chiropractic treatment that caused these changes. It could be that other factors, such as natural history, led to the improvement in symptoms, and the altered N30 SEP ratios may simply reflect the symptomatic relief. However, we do not think this is the case, because we have previously reported that a single session of chiropractic adjustments alone in a subclinical population also leads to a significant decrease in the N30 SEP peak ratio (ie, decreased MU to M + U ratio). [14, 15]
Central Reciprocal Inhibition and Pain Disorders
The changes observed in dual SEP ratios after several weeks of chiropractic care in a chronic pain population suggest that this treatment option may improve gating of peripheral afferent input to the brain, thus improving impaired SMI in cortical motor areas and improving processing of motor programs. Impaired SMI and defective motor programming is known to be present in various chronic pain populations [6–57] and is implicated in the clinical symptomatology. [58] We know from the literature that in normal circumstances, afferent input to the motor system leads to finely tuned activation of neural elements and ultimately results in the correct execution of movement. [23] Multiple experimental and clinical studies have confirmed the importance of sensory feedback to the motor system. [23, 59] Thus, distorted sensory information is thought to disturb SMI and impair accurate motor control. In normal circumstances, 2 inputs that engage the sensory system have a reciprocally inhibitory action that gates the total amount of signal at all central levels, spatially and temporally limiting the amount of input engaging the CNS. This is thought to prevent sensory “overflow.” The defective gating may cause an input-output mismatch in specific motor programs, and such mismatches in motor programs may in themselves lead to production of distorted sensory information and issue of less than ideal motor commands. In this way, the chronicity of the problem can be maintained via a self-perpetuating mechanism. The reduced frontal N30 SEP peak ratio observed in the current study after 12 weeks of chiropractic care may reflect a normalization of pain-induced central maladaptive plastic changes and may reflect one mechanism for the improvement of functional ability reported following chiropractic adjustment or manipulation.
Other than pain, additional sensory symptoms are also frequently found in many chronic pain groups, [60, 61] and sensory manipulation has been reported to modify clinical severity. [62, 63] Interestingly, one of the subjects in the current study complained that his arms felt like “Popeye” arms, as they felt larger and heavier than he knew they were. As the 12 weeks of chiropractic care progressed, this subject reported to one of the examiners that he no longer experienced his arms as “Popeye” arms and that they no longer felt heavy or abnormally large. Several of this subject’s central SEP peak ratios were greater than 1 at both baseline and after the 2–week control period. This was the case for his N13 and N30 complexes at baseline and for his N13, N18, and N30 SEP complexes after the 2–week control period. Figure 1 illustrates what this looks like for his N30 SEP complex, where the MU trace is actually larger in amplitude compared with his M + U traces. After the 12 weeks of chiropractic care, when he was also feeling better symptomatically, this was reversed, and all of his MU traces for all SEP peak complexes were smaller in amplitude than his M + U trace, indicating a greater level of central reciprocal inhibition was occurring.
Figure 1.
Electrode placement
A, Electrode placement viewed from above.
B, Lateral view of electrode placement and attachment on a model's head and neck.
C, Placement of the median and ulnar nerve-stimulating electrodes.
Although the functional importance of this gating is not fully understood, it is thought to play an important role in maintaining an accurate inner body schema, by preserving the spatial separation of the 2 stimuli. [16] Reciprocal sensory inhibition would enhance the contrast between stimuli, so that information from adjacent body parts is perceived and, more importantly, processed separately. Thus, if sensory “overflow” occurs, then incomplete processing of this incoming signal may occur in the brain, resulting in its perceiving not only excessive, but also spatially distorted information. This may have been why our subject felt as if he had “Popeye arms,” although he knew this not to be real.
Central Reciprocal Inhibition and Neurological Disorders
As mentioned, conditions such as dystonia16 and Huntington’s disease23 are known to have increased dual SEP ratios. The increased SEP ratios that have previously been observed for those with dystonia [16] and Huntington’s disease [23] suggest that these individuals receive distorted and excessive (ie, not spatially filtered) afferent input from their affected limbs, which may potentially cause their motor system to transform these afferent inputs into abnormal “unhealthy” motor outputs. The chronic pain subjects in our study with increased central SEP ratios may also have been receiving excessive afferent input affecting their upper limb SMI and motor control. The individual whose traces are depicted in Figure 1 was a piano player, and his chronic neck and arm pain could be considered a form of chronic overuse injury, similar in some respects to some types of dystonia. Regardless, this subject exhibited impaired afferent-input gating, as has previously been shown with dystonia that reversed to a more healthy-looking gated signal after 12 weeks of chiropractic care. The results of our study therefore suggest it is worth investigating whether chiropractic care is beneficial for individuals with other neurological conditions that are associated with abnormal central somatosensory gating.
Limitations and Future Studies
This study was not designed to test the efficacy of chiropractic care for treating chronic pain; therefore, conclusions about efficacy cannot be drawn from our findings. The study did not include randomization with an adequate control group, thus limiting the interpretations that can be made about the changes in pain observed in the trial. Causation cannot be claimed. The patients were heterogenous with varying types and degrees of upper limb and cervical pain. Although the reductions in current pain (2.3) and pain from the previous week (1.9) exceeded the values for a minimum clinically important difference for nonspecific neck pain (0.8), they were not considered to reflect a substantial clinical benefit (2.7) when measured using a VAS.64 It is also important to note that one of the researchers was also the treating chiropractor, which may have had an effect on patient response.
It is imperative that future large studies explore the relationship between pain changes and cortical intrinsic inhibition further before any firm conclusions can be made. On average, pain now dropped from 4.1 to 1.8 on the VAS (P = .02), and pain last week dropped from 6.4 to 4.5 (P = .01). The control period was not matched to the period of chiropractic care; thus, changes in dual SEP ratios may occur after 12 weeks, even without chiropractic care. It is also possible that the nonsignificant positive correlations observed between pain levels and N30 MU to M + U ratio (r = 0.62 and r = 0.51) were not significant because of the small sample size. There was an imbalance between sexes in subject numbers so interactions between sex and the primary outcome cannot be ruled out. Follow-up in larger samples with and without pain would also be valuable in confirming whether larger cortical ratios are truly associated with chronic pain and lower cortical ratios reflect reduced symptomatology.
Conclusion
The P22–N30 complex dual SEP ratio appears to be a measure that could be used alongside clinical measures in future clinical trials to document neurophysiological changes that accompany treatment of chronic pain. The observations of the 6 subjects in the present study suggest that 12 weeks of chiropractic care may improve suppression of SEPs evoked by dual-upper-limb nerve stimulation at the levels of the motor cortex, premotor areas, and/or subcortical areas such as basal ganglia and thalamus. It is possible these findings reflect reduced cortical processing caused by increased gating of excessive sensory information due to the 12 weeks of chiropractic care, and that this may be one of the mechanisms by which chiropractic care improves function and reduces pain for chronic pain patients. However, further studies are needed to elucidate the role and mechanisms of these cortical changes, confirm causality, and confirm their relationship to chronic pain patients’ clinical presentation and ability to perform daily tasks.
Practical Applications
The results of this study suggest that 12 weeks of chiropractic care may improve
gating of peripheral afferent input to the brain, thus improving impaired SMI
in cortical motor areas and improving processing of motor programs.
A few of the chronic pain patients in this study exhibited abnormal gating
of proprioceptive afferent input prior to chiropractic care (their medial
and ulnar N30 amplitudes were larger than their medial + ulnar amplitudes),
which were reversed after the 12 weeks of chiropractic care (noting that
the current study design cannot prove causation).
The P22–N30 complex dual SEP ratio appears to be a measure that could
be used alongside clinical measures in future clinical trials to document
neurophysiological changes that accompany treatment of chronic pain.
This study supports previous research that suggests that altered sensory
processing and motor control may be implicated in the development
of chronic neck pain.
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