Hypoaesthesia occurs with sensory hypersensitivity in chronic whiplash – further evidence of a neuropathic condition Andy Chien, B.Phty (Hons) PhD Candidate, Division of Physiotherapy The University of Queensland QLD 4072 Australia Eli Eliav, DMD, PhD University of Medicine and Dentistry New Jersey Newark, New Jersey, 07101, United States Michele Sterling, PhD MPhty BPhty Grad Dip Manip Phty Associate Director Centre of National Research on Disability and Rehabilitation Medicine (CONROD) The University of Queensland, Mayne Medical School Herston Road, Herston QLD 4066 Australia & Senior Lecturer, Division of Physiotherapy The University of Queensland, QLD 4072 Australia Corresponding Author: Michele Sterling Tel: +61 7 3365 5344 (direct) Fax: +61 7 3346 4603 Email: [email protected] Keywords: Whiplash injury, Sensory hypersensitivity, Hypoaesthesia, Quantitative Sensory Testing 1 ABSTRACT Hypersensitivity to a variety of sensory stimuli has been shown to exist in whiplash associated disorders and may be indicative of peripheral nerve involvement. This cross- sectional study utilized Quantitative Sensory Testing including vibration, thermal and electrical detection thresholds to provide an indirect measure of primary afferents that mediate innocuous and painful sensation. Pain thresholds and psychological distress (SCL-90-R) was also measured. Thirty one subjects with chronic whiplash (>3 months, NDI: 49 ± 17) and 31 controls participated. The whiplash group demonstrated elevated vibration, heat and electrical detection thresholds at most hand sites when compared to controls (p<0.05). Electrical detection thresholds in the lower limb were no different from controls (p=0.83). Mechanical and cold pain thresholds were lower in the whiplash group (p<0.05) with no difference between the groups for heat pain thresholds (p>0.1). SCL-90 scores were higher in the whiplash group but this did not impact on any of the sensory measures. A combination of pain threshold and detection measures best predicted the whiplash group from the controls. Sensory hypoaesthesia and hypersensitivity co-exist in the chronic whiplash condition. The hypoaesthetic changes (elevated detection threshold) consistent with other clinically established neuropathic conditions may indicate peripheral nerve dysfunction. 2 INTRODUCTION Whiplash associated disorders (WAD) remain one of the most debated musculoskeletal conditions. Sensory disturbances including hypersensitive responses to mechanical, thermal and electrical stimulation have been consistently shown to be a feature of both the acute and chronic stages of the whiplash condition (Curatolo et al 2001, Moog et al 2002, Sterling et al 2003a). Importantly some of the sensory changes have been shown to be associated with poor functional recovery (Kasch et al 2004, Sterling et al 2005). It is generally acknowledged that the sensory hypersensitivity represents augmented central nervous system pain processing mechanisms (Curatolo et al. 2001, Sterling et al. 2003a). However, some of the changes, particularly cold hyperalgesia and sympathetic nervous system dysfunction, may be indicative of peripheral nerve pathology (Sterling et al. 2003a). This proposal has some basis as animal and cadaver models simulating whiplash impact have shown that the nonphysiologic kinematic movement during the impact induces stresses in cervical neural tissue such as the nerve roots and spinal ganglia resulting in mechanical compromise sufficient to cause structural damage (Cusick et al 2001, Ortengren et al 1996, Taylor and Taylor 1996). Furthermore, mechanosensitivity has been demonstrated with clinical tests designed to provoke the brachial plexus as well as mechanical hyperalgesia over upper limb nerve trunks (Greening et al 2005, Ide et al 2001, Sterling et al 2002a). Despite these findings, standard clinical neurological examination is often normal and deficits in nerve conduction studies are rarely found (Alpar et al 2002, Barnsley et al 1998). Although nerve conduction studies are reliable and reproducible when carried out 3 by a single examiner (Chaudhry et al 1994), they are limited by their ability to assess only large myelinated nerve fibres and the invasive nature of the technique. Quantitative Sensory Testing (QST) is proving to be a valuable tool to advance the classification of specific disorders and may be useful in illuminating the underlying mechanism of pain disorders (Edwards et al 2005). Rolke et al., (2006) have demonstrated the validity of using comprehensive QST to obtain a complete somatosensory profile in order to characterize patients with suspected neuropathic conditions but such testing has never been undertaken in a WAD cohort. In a cross-sectional study design, comprehensive QST was used to further investigate the sensory presentation of chronic WAD. Different modalities were incorporated to provide an indirect measure of primary afferents that mediate both innocuous and painful sensation. We hypothesised that patients with chronic WAD would demonstrate elevated detection thresholds as well as widespread sensory hypersensitivity. MATERIALS AND METHODS Subjects Thirty one volunteers (25 females, mean (SD) age 35.3 ± 10.7 years) with neck pain (3 months to 3 years duration) as a result of a motor vehicle crash were recruited. Subjects fulfilled the Quebec Task Force Classification criteria of WAD II, neck complaints and musculoskeletal signs but without conduction loss on clinical neurological examination (Spitzer et al 1995). Subjects were excluded if they experienced concussion, loss of consciousness or head injury as a result of the accident, a previous history of neck or upper quadrant pain that required treatment and/or a diagnosed psychiatric disorder. The 4 whiplash subjects were recruited via primary care practices and from advertisement within radio and print media. Thirty one healthy volunteers (25 females, mean age 31.4 ± 8.9) also participated in the study. The control group was recruited from the general community provided they had never experienced trauma or injuries to the cervical spine, head, and upper quadrant requiring treatment. The study was approved by the institutional medical research ethics committee. All the subjects were unpaid volunteers and all gave written informed consent before inclusion. Brachial Plexus Provocation Test (BPPT) The BPPT which has been used in previous studies of whiplash (Sterling et al. 2003a, Sterling et al 2002b) was performed. The angle of elbow extension was measured at pain threshold using a standard goniometer aligned along the mid-humeral shaft, medial epicondyle and ulnar styloid (Balster and Jull 1997, Sterling et al. 2002b). Subjects indicated their pain during the test on a 10cm visual analogue scale (VAS) where 0 indicated no pain and 10 was the worst pain imaginable. Quantitative sensory testing (QST) Pressure pain thresholds (PPTs) PPT’s were measured using a pressure algometer (Somedic AB, Farsta, Sweden) with a probe size of 1 cm2 and application rate of 40 kPa/s. Test sites included the articular pillars of C5/6, nerve trunk of the median nerve at the elbow bilaterally (palpated on the medial side of the biceps just before it forms its tendon) and at a bilateral remote site (muscle belly of tibialis anterior). The subjects depressed a button when the sensation under the probe changed from one of pressure alone to one of pressure and pain (Sterling 5 et al 2002b). Triplicate recording were taken at each site and the mean values used for analysis. Thermal (hot, cold) pain thresholds (TPTs) TPTs were measured using the Thermotest system (Somedic AB, Farsta, Sweden) over the mid-cervical spine and the distal aspect of C7/8 dermatomes (dorsal aspect of the hand). The temperature was preset to either increase or decrease at a rate of 1°C/sec from a baseline of 30°C. The subject pressed a switch when the cold or warm sensation first became painful (Hurtig et al 2001). The mean of three trials at each site were calculated for analysis. Vibration detection thresholds (VTs) A vibrometre (Somedic AB, Sweden) with a tissue displacement range of 0.1±400 µm and a constant frequency of 120 Hz was used. In order to familiarise the subjects with the vibration stimulus, 3 trials of the test stimuli, or until the subject was able to consistently indicate the onset of the stimulus, were applied over the muscle belly of brachioradialis. Measures were taken over areas of the hand innervated by distal aspect of the C6 (palmar aspect of the 1st metacarpal), C7 (palmar aspect of 2nd metacarpal; dorsum of the 2nd metacarpal) and C8 dermatomes (dorsum of the 5th metacarpal). Subjects indicated when the vibration first appeared, the perception threshold (VPT), and when it disappeared, the disappearance threshold (VDT). The vibration threshold (VT) was the average of VPT and VDT. Triplicate recordings were taken at each site and the mean values used for analysis. Thermal (hot, cold) detection thresholds (TDTs) 6 TDTs assess the function of afferent small myelinated A-delta fibres (cold sense) and unmyelinated C-fibres (warm sense) (Adriaensen et al 1983, Fowler et al 1988, Hallin et al 1982). Incorporating the method of limits, the Thermotest (Somedic AB, Sweden) was used to measure TDTs over areas of the hand innervated by the C7 (dorsum over the 2nd metacarpal) and C8 (dorsum of the 5th metacarpal) dermatomes. The temperature was preset to either increase or decrease at a rate of 1°C/sec from a baseline of 30°C. The patient pressed a switch when they first detected the sensation of warmth or cold. Electrocutaneous detection and pain thresholds A non-noxious method of electrocutaneous stimulation was used in a method of limits procedure using the Neurometer device (Neurotron., Baltimore, USA). Sites tested were those innervated by C5/6 (anterior shoulder, inferior to shoulder joint line), C7 (distal phalanx of index finger); C8 (distal phalanx of 5th digit) and Tibialis Anterior as a remote site. Three different sinusoidal frequencies (2000Hz , 250Hz and 5Hz) were applied to each site in order to evoke a response from a different subpopulation of sensory fibre (Katims et al 1986, Katims et al 1987). The subjects reported when they first perceived the sensation (perception threshold) and again at the intensity at which they can no longer feel the sensation (disappearance threshold). The mean of these two values were calculated and recorded three times for analysis. The same sites used to determine current detection thresholds were used to determine pain threshold but only a frequency of 250Hz was used. As the stimulus intensity increased, the subject released a button when they first perceived the stimulus as painful. The procedure was repeated three times with the mean score recorded as electrical pain threshold. 7 Ratios were obtained by dividing the electrocutaneous pain threshold over the electrocutaneous detection threshold. Low intensity electrical stimulation activates large A-beta nerve fibres. Current evoked pain at or close to detection threshold (ratio of less than 2:1) has been suggested to be a substrate of A-beta fibre allodynia (Sang et al 2003). Sympathetic Vasoconstrictor Reflex (SVR) A laser Doppler (Moor Instruments, Devon UK) was used to assess sympathetic nervous system (SNS) function (Schurmann et al 1999). Electrodes were attached to the thenar eminence of both hands. The test was performed with subjects in a comfortable supine position, arms resting at heart level. After a period of acclimatization and normal breathing, participants were asked to take a sudden deep breath. This provocation manoeuvre (inspiratory gasp) is known to cause a short sympathetic reaction and cutaneous vasoconstriction (Schurmann et al. 1999) and has been used in previous investigation of whiplash (Sterling et al 2005). The procedure was repeated three times. Two quotients (SRF and QI) which describe vasomotor reflexes following the inspiratory gasp were calculated. SRF value represents the relative drop of the curve after the manoeuvre with the QI parameter also being influenced by the duration of perfusion decrease (Schurmann et al. 1999). Questionnaires All participants completed the Neck Disability Index (NDI) (Vernon and Mior 1991) and The Symptom Check List 90-R (SCL-90-R). The NDI was used to assess the extent of perceived functional disability. The SCL-90-R assessed the psychological well being of participants. 8 Procedure Once the informed written consent was obtained, testing was performed in the following order: SVR, BPPT, PPT (tibialis anterior, median nerve, C5/6), TDTs, TPTs, VTs, electrocutaneous detection (2000, 250, 5 Hz) and pain thresholds (250 Hz). The SVR testing was performed in a temperature-controlled laboratory. The temperature was set at 20°C, lights were dimmed and ambient noise was kept low. The rest of the testing was completed in a standard air-conditioned laboratory. For all the measures, the left side was tested first followed by the right side. Statistical analysis The SPSS 12.0 statistical package for Windows was used for analyses. A two sample t- tests determined within subject side to side differences for all measures. A multi- variate analysis of covariance (MANCOVA) was used to compare differences between the chronic whiplash group and controls. SCL-90-R scores were entered as covariates in the analysis. Receiver Operating Characteristic (ROC) Analysis was determined to examine the ability of each variable to discriminate between the groups. Variables with a greater predictive capacity based on the significance level (p < 0.01) were entered in a logistic regression analysis to determine the best combination to predict group membership. The regression analysis was then subjected to cross-validation analysis (leave one out) to examine its reliability and generalisability. To determine differences in sensory measures between whiplash participants with or without arm pain, Mann-Whitney U test was used. The presence of arm pain was 9 defined as any pain (spontaneous or evoked) distal to the shoulder reported by the participants. For all analyses significance was set at p<0.05. RESULTS Demographic details For the whiplash group, the mean (SD) symptom duration post injury was 16 ± 11 months. Twenty-four patients were involved in ongoing compensation claims; four had settled their claims and three had no compensation involved. The mean (SD) NDI score was 45.9% ± 18.8%, a moderate level of disability (Vernon and Mior 1991). Forty-five percent of whiplash patients reported arm pain at the time of testing and 66% experienced headache. Side to side differences There were no side to side differences for any variable in both groups (all p>0.05). The mean of left and right sides were calculated and used for further analysis. BPPT The whiplash group demonstrated less elbow extension at pain threshold (-22.3 ± 27.4º) (p=0.05) and higher VAS scores (2.4 ± 2.3) compared to the control group (elbow extension: -11.0 ± 5.9º; VAS: 0.7 ± 1.1) (p=0.05). Quantitative sensory testing Pain thresholds The whiplash group demonstrated lower PPT’s at all test sites compared to controls (p<0.05) (Table 1) 10