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Fatty infiltrate in the cervical extensormuscles is not a feature of chronic,insidious-onset neck pain

J. Elliotta,b,c,*, M. Sterlinga, J.T. Noteboomb, R. Darnella,G. Gallowayc, G. Julla

aDivision of Physiotherapy, School of Health and Rehabilitation Sciences, The University of Queensland,

Brisbane, Australia, bDepartment of Physical Therapy, Rueckert-Hartman School for Health Professions,

Regis University, Denver, Colorado, USA, and cCentre for Magnetic Resonance,

The University of Queensland, Brisbane, Australia

Received 24 July 2007; received in revised form 23 October 2007; accepted 7 November 2007

AIM: To investigate the presence of fatty infiltrate in the cervical extensor musculature in patients with insidious-onset neck pain to better understand the possible pathophysiology underlying such changes in chronic whiplash-asso-ciated disorders (WAD).

MATERIALS AND METHODS: A sample of convenience of 23 women with persistent insidious-onset neck pain (meanage 29.2 6.9 years) was recruited for the study. Magnetic resonance imaging (MRI) was used to quantify fatty infil-tration in the cervical extensor musculature. Quantitative Sensory Testing (QST; pressure and thermal pain thresholds)was performed as sensory features are present in chronic whiplash. Self-reported pain and disability, as well as psy-chological distress, were measured using the Neck Disability Index (NDI) and the General Health Questionnaire-28(GHQ-28), respectively.

RESULTS: Measures were compared with those of a previous dataset of chronic whiplash patients (n 79, mean age29.7 7.8 years). Using a classification tree, insidious-onset neck pain was clearly identified from whiplash(p< 0.001), based on the presence of MRI fatty infiltrate in the cervical extensor musculature (0/102 individuals)and altered temperature thresholds (cold; 3/102 individuals).

CONCLUSION: Fatty infiltrates in the cervical extensor musculature and widespread hyperalgesia were not featuresof the insidious-onset neck pain group in this study; whereas these features have been identified in patients withchronic WAD. This novel finding may enable a better understanding of the underlying pathophysiological processesin patients with chronic whiplash. 2007 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction

Chronic whiplash-associated disorder (WAD) is acomplex syndrome involving changes in the sensory,

motor, and psychological systems.1e

3 Recently,alterations (fatty infiltration) were demonstratedin the cervical extensor musculature of patientswith chronic WAD using magnetic resonanceimaging

(MRI).4 The fatty infiltration was widespread andpresent bilaterally in all cervical extensor musclesat all segments, albeit there was significantlymore fatty infiltrate in the sub-occipital and multi-

fidus muscles. The cause of this fatty infiltrate couldnot be determined, but it was not related to age,body mass index, self-reports of pain and disability,or symptom duration. It was suggested that thefatty infiltrate might be a product of either generaldisuse or a minor nerve injury, irritated, and subse-quently, demyelinated nerve tissue resulting froman acute inflammatory process or a combinationof these factors.5 General disuse would seem themost reasonable explanation given the widespread

* Guarantor and correspondent: J.M. Elliott, Regis University,3333 Regis Blvd, G-4, Rueckert-Hartman School for Health Pro-fessions, Department of Physical Therapy, Denver, Colorado80221-1099, USA. Tel.: 1 303 964 5484; fax: 1 303 964 5474.

E-mail address:jelltt@regis.edu(J. Elliott).

0009-9260/$ - see front matter 2007 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.crad.2007.11.011

Clinical Radiology (2008) 63, 681e687

mailto:jelltt@regis.edumailto:jelltt@regis.edu

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fatty infiltrate in the extensor musculature of theseWAD patients.

If general disuse is the cause, then it might beexpected that patients with chronic neck pain of aninsidious-onset would also, to some extent, dem-onstrate these findings. To test this hypothesis, we

undertook this preliminary study of patients withchronic insidious-onset neck pain and measuredthe extent of fatty infiltration in the cervicalextensor muscles. In addition, quantitative sensorymeasures of thermal and pressure pain thresholds,as well as a measure of psychological stress, wereobtained to better understand the similarities anddifferences in presentation between these patientsand those with chronic WAD. This enabled us to ex-plore any associations between these features andfatty infiltrate in muscles. Alterations in the sen-sory measures can indicatethepresence of abnor-mal central pain processing,2,3 and the presence offatty infiltrate in muscle may be associated withminor and/or major nerve injury.6

Materials and methods

A sample of convenience encompassing 23 women(mean age 29.2 6.9 years, range of 18e45 years,mean duration of pain 33.7 20.6 months) sufferingfrom persistent, insidious-onset neck pain was usedin the study age to parallel the whiplash group.Volunteers with persistent, insidious-onset neck

pain were recruited through advertising in localphysiotherapy practices and within the local univer-sity fraternity. Participants were included if theysuffered from insidious-onset neck pain that hadpersisted for 3 months or longer. Volunteers wereexcluded if the onset of neck pain was related to amotor vehicle crash or any other incident of traumaor if they had been diagnosed with any central or pe-ripheral nervous system disorder; were either preg-nant or thought to be pregnant; reported beingclaustrophobic; or did not meet institutional crite-ria to undergo MRI. The parallel data of the 79WAD subjects (mean age 29.7 7.8 years, meanduration of pain 20.3 9.6 months) from apreviousstudy were used for comparative purposes.4

This project was granted approval by Institu-tional Medical Research Ethical Committees. Allparticipants provided written informed consentbefore inclusion in the study.

MRI analysis

The principle sources of a MRI signal are fatand soft-aqueous tissue (e.g. skeletal muscle) and anyabnormalities causing a change in fat or water

content can result in altered signals on T1 or T2-weighted sequences. T1-weighted images are verysensitive to the presence of fatty deposition in mus-cle7 and as a result, were chosen to quantify fattyinfiltration in the cervical extensor musculature.The measure of relative fat withinthe muscle was

created as described previously8

by developinga pixel intensity profile using MRIcro software(www.mricro.com). The measure was the ratiobetween the pixel intensities of each muscle tothat of a standardized region of intermuscular fat,thus allowing comparisons between individuals.4,9

For the purpose of this study, a fat score was deter-mined for each cervical muscle by calculating themean value across segments and sides (C3eC7).Rectus capitis posterior minor was measured atthe C0eC1 level and rectus capitis posterior majorwas measured at the C2 level. The fat score forthe sub-occipital musculature was also determinedby calculating the mean value for the two muscleson each side, to provide a single fat score for thesemuscles.

Thermal pain thresholds

Hot and cold thermal pain thresholds were mea-sured over the cervical spine using QuantitativeSensory Testing (Medoc, Israel e www.medoc-web.com). A Peltier thermode was applied directlyto the glabrous skin over the posterior cervicalspine and held in place manually. The thermode

was preset at a baseline temperature of 32

Cwith the rate of temperature change being 1 C/s.To measure cold pain thresholds (CPT) and heatpain thresholds (HPT), participants were askedto push a patient-controlled button when the coldor warm sensation first became painful.10 Triplicaterecordings were obtained for each site and themean value was used for analyses.

Pressure pain thresholds (PPT)

PPT were measured using a pressure algometer(Somedic AB, Farsta, Swedenewww.somedic.com)at two cervical spine sites bilaterally (over thespinous processes of C2 and C5) and at a remotesite bilaterally (the muscle belly of the tibialis ante-rior). The measures for the C2 and C5 sites werecombined and the mean value was used as a mea-sure for PPT_local thresholds. The measures overthe left and right tibialis anterior muscles werecombined and the mean value was used as a mea-sure forPPT_remote thresholds. These sites havebeen previously used in investigations ofboth idio-pathic 11 and whiplash-induced neck pain.12 Partic-ipants were requested to push a button when the

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sensation changedfrom one of pressure to one ofpressure and pain.13 Triplicate recordings were ob-tained at each site and the mean value for the rightand left sides was used for analyses.

Self-reported pain and disability

Self-reported pain and disability was assessedusing the Neck Disability Index (NDI), which hasbeen shown to be reliable and valid.14,15 A higherNDI score (out of 100) indicates greater pain anddisability.

Psychological questionnaire

The General Health Questionnaire-28 (GHQ-28) isa 28-item measure of emotional distress in a medicalsetting. The total score can be used as a measure of

psychological distress. The GHQ-28 has been used inprevious research of WAD.16

Statistical analysis

One-way analysis of variance (ANOVA) was used toinvestigate any difference between the measuresof total average fatty infiltrate in the sub-occipitaland cervical extensor muscles between the insidi-ous-onset and WAD groups, as well as measuresof self-reported pain and disability (NDI), psycho-logical stress (GHQ-28), and of the quantitativesensory tests (thermal and pressure). Analyses of

covariance (ANCOVAs) were also performed withthe total fat scores (TOTAL_UPPER and TOTAL_FAT)as the dependent variable and NDI as the covariateinto the final between groups analysis. Lastly, ananalysis was undertaken to determine whetherinsidious-onset neck pain could be discriminatedfrom WAD on the basis of average fat (fat indicesaveraged by all muscles), sensory tests, and scoreson the NDI and GHQ-28. In the first instance,a forward-step regression model was used; how-ever, logistic regression failed, due to the distinctdifferences in fat measures between the insidious-

onset neck pain and WAD groups. Therefore, aclassification tree approach17 was taken using all

variables measured initially, followed by a secondanalysis in which fatty infiltration scores were re-moved.The R implementation of Thernau and At-kinson18 was used in analysis.

Results

Table 1 presents the demographic characteristicsand the results of the questionnaire on generaldistress (GHQ-28) for the two groups. There wereno significant group differences for age or BMI(p 0.77 and 0.17, respectively). Participantswith chronic, insidious-onset neck pain had signif-icantly lower NDI scores (p< 0.001), but neck painof significantly longer duration (p< 0.001) thanthose with chronic WAD. The groups also differedwith respect to GHQ-28 scores with the insidious-onset neck pain participants reporting significantlylower distress than the group with chronic WAD(p< 0.001).

MRI analysis

There was a difference in the fat indices of allmuscles with WAD participants demonstrating sig-nificantly higher amounts of total fatty infiltrationwhen compared with the insidious-onset neck painparticipants (p< 0.001).Table 2presents the totalaverage fat index scores across the cervical exten-sor muscles for the participants with insidious-

onset neck pain and chronic WAD.Fig. 1illustratesthe mean (SD) fat index scores for the cervicalextensor musculature between the two groups.Fig. 2 illustrates the outlined region of interestfor the multifidus muscle at the C6 segmental levelon axial MRI for a participant with insidious-onsetneck pain and chronic WAD.

Thermal pain thresholds

There was a significant difference between thecold (CPT) and hot (HPT) pain thresholds between

the two groups with participants with chronic WADdemonstrating reduced CPT (p< 0.001) and HPT

Table 1 Group demographics and results of the General Health Questionnaire-28 (GHQ-28)

Group Age (years) Body mass index (kg/m2) Neck Disability Indexa Duration (months)a GHQ-28-totala

Insidious-onsetneck pain (n 23)

29.2 (6.9) 23.3 (4.9) 21.9 (7.5) 33.7 (20.6) 15.6 (7.5)

Whiplash-associateddisorders (n 79)

29.7 (7.8) 25.1 (5.7) 45.5 (15.9) 20.3 (9.6) 30.5 (12.8)

Data are mean (SD).a p< 0.001.

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thresholds (p 0.001) when compared with partic-ipants with chronic, insidious-onset neck pain(Table 3).

Pressure pain thresholds

There was a significant difference in both the

PPT_local and PPT_remote pain thresholdsbetweenthe two groups with participants with chronic WADdemonstrating reduced thresholds when comparedwith participants with chronic, insidious-onsetneck pain (p< 0.001;Table 3).

Associations between NDIand fat measurements

Within groups there was no association betweenNDI and fat levels TOTAL_UPPER_FAT; p 0.15;TOTAL_FAT; p 0.94). Thus, NDI does not signifi-

cantly influence the amount of fat infiltrate inthe cervical extensor musculature and approxi-mately 70% of the total fat measure variance isexplained by other factors (R2 0.67 and 0.69).Fig. 3a and b are scatter plots of NDI and TOTAL_-UPPER_FAT and TOTAL_FAT measures for bothgroups, respectively.

Classification tree

The classification tree analysis included the follow-ing discriminating variables: GHQ-28, NDI, duration,CPT, HPT, PPT_local, PPT_remote, and average cer-vical fat index score. The analysis revealed that thestrongest features distinguishing the two groups

were (1) the fat index scores and (2) CPT. In the firstinstance, the classification tree yielded a 0%misclassification rate based on fatty infiltrates; in-dicating that the insidious-onset neck pain groupwas clearly distinguished from the chronic WADgroup. The cut-off value for average fat indexfor insidious-onset neck pain was

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could be clearly distinguished from the WAD groupbased on average muscular fat and cold painthresholds.

It is difficult to definitively ascribe duration ofsymptoms and disuse as either the primary or theonly cause of fatty infiltrate in the WAD group basedon this study for two reasons. First, the insidiousgroup showed low values of fatty infiltrate, similarto previous data from healthy subjects4 and second,the insidious group had an average symptom dura-tion 1 year greater than the WAD group (insidiousgroup 2.9 years and the WAD group 1.8 years).If disuse were the primary or only cause of fattyinfiltrate, then it would be expected to be presentin those suffering neck pain of a longer duration.Nevertheless, it is possible that the factors involvedin disuse are more closely related to higher levels ofpain and disability, which affect activity levels,rather than the longer duration of symptoms. It isnotable that the WAD group, consistent with previ-ous studies, had higher levels of pain and disabilitywhen compared with the insidious-onset group,11,19 but the NDI score was shown not to significantlyinfluence the amount of fat infiltrate in the cervical

extensor muscles. As illustrated inFig. 3, many ofthe WAD participants had NDI scores

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those with chronic whiplash. Although group differ-ences were apparent for all stimuli, it is notable thatcold pain thresholds most clearly distinguished thegroups in the classification tree. The other sensorymeasures of pressure and heat pain thresholds didnot emerge as significant factors, but care should betaken with interpretation, as this could be a factor ofpower of the study. Nevertheless, cold allodynia or

intolerance has been shown to be a consistent pre-dictor o fhigher levels of pain and disability in chronicWAD.12,20 Additionally, decreased cold pain thresh-olds (cold hyperalgesia) are a feature of neuropathicpain.21,22 The co-occurrence of cold allodynia andmuscle fatty infiltrate in chronic WAD is interestingand may suggest common underlying mechanisms,possibly involving peripheral nerve injury. It is knownthat muscular fatty infiltration, which results inincreased signal on T1-weighted MRI sequences, isa hallmark ofchronicity6 and may represent chronicdenervation.23e25 Further research into the possibil-ity of nerve injury may help to better understand theprocesses underlying chronic whiplash pain. In addi-tion the temporal development of fatty infiltrate inmuscle needs to be established.

It is noteworthy that participants with insidious-neck pain, despite long-standing symptoms, didnot show specific signs of sensory hypersensitivity,psychological distress, or fatty changes in theircervical extensors. The difference in sensorypresentation between the two groups has beenpreviously observed11 and could indicate that aug-mented central pain processing does not playa large role in neck pain of insidious-onset. This

is in contrast to chronic whiplash where suchprocesses are thought to be important.2,3,10,26 Itappears that insidious-onset neck pain has a lesscomplex presentation than whiplash and mayreflect a condition primarily involving peripheralnociceptive activity.

In conclusion, the results of this study providepreliminary data that female patients (18e45

years) suffering from persistent insidious-onsetneck pain do not show quantifiable MRI changesin the fat content of the cervical extensor muscu-lature and that their levels of fat mirror those withno history of neck pain. In addition to a lack ofmuscle changes, participants with insidious-onsetneck pain did not demonstrate widespread sensi-tivity to sensory stimuli and the presence of thesefeatures is consistent with abnormal central pain-processing mechanisms; such as seen in somesubjects with acute and chronic WAD.

Acknowledgements

The authors thank Kathy Francis for her contribu-tions in completing this study.

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Figure 3 (a) Scatter plot for NDI scores and TOTAL_UPPER_FAT and (b) TOTAL_FAT scores between participants withchronic WAD and chronic insidious-onset neck pain.

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