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Generalised muscular hyperalgesia in chronic whiplash syndrome
Pain 83 (1999) 229±234 www.elsevier.nl/locate/pain
Generalised muscular hyperalgesia in chronic whiplash syndrome Mona Koelbaek Johansen a, Thomas Graven-Nielsen b,*, Anders Schou Olesen c, Lars Arendt-Nielsen b b
a Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Fredrik Bajers Vej 7D-3, DK9220 Aalborg E, Denmark c The Pain Clinic, Aalborg Hospital, Aalborg, Denmark
Received 10 December 1998; received in revised form 31 March 1999; accepted 21 May 1999
Abstract The whiplash syndrome has immense socio-economic impact. Despite extensive studies over the past years, the mechanisms involved in maintaining the pain in chronic whiplash patients are poorly understood. The aim of the present experimental study was to examine the muscular sensibility in areas within and outside the region involved in the whiplash trauma. Eleven chronic whiplash patients and 11 sex and age matched control subjects were included in the study. Before the experiment, the whiplash patients had pain in the neck and shoulder region with radiating pain to the arm. Five patients reported pain that was more widespread. The somatosensory sensibility in the areas over the infraspinatus, brachioradial, and anterior tibial muscles was assessed by pressure stimulation, pin-prick stimulation, and cotton swap stimulation. Infusion of hypertonic saline (5.85%, 0.5 ml) into the infraspinatus and anterior tibial muscles was performed to assess the muscular sensibility and referred pain pattern. The saline-induced muscle pain intensity was assessed on a continuous visual analogue scale (VAS). The distribution of pain was drawn on an anatomical map. The pressure pain thresholds were signi®cantly lower in patients (P , 0:01) compared with controls: infraspinatus (mean 152.2 vs. 172.7 kPa), brachioradial (mean 70.0 vs. 363.8 kPa), and anterior tibial muscle (mean 172.7 vs. 497.8 kPa). The skin sensibility to pin-prick stimulation and cotton swap stimulation was not different between patients and controls. Infusion of hypertonic saline caused signi®cantly higher VAS scores with longer duration in patients compared to control subjects (P , 0:01). The area under the VAS-time curve was signi®cantly (P , 0:01) increased in patients compared to control subjects after injection into the infraspinatus muscle (mean 4138.1 vs. 780.0 cm s) and anterior tibial muscle (mean 4370.8 vs. 978.7 cm s). The saline infusion caused local pain de®ned as pain located around the injection site and referred pain areas not included in the local pain area. The area of local and referred pain were signi®cantly larger in patients compared to control subjects (P , 0:01). In the control group, the referred pain areas to infusion of hypertonic saline into the anterior tibial muscle were found at the dorsal aspect of the ankle. In contrast, the areas of referred pain were quite widespread in the patient group with both distal and proximal referred pain areas. In the present study, muscular hyperalgesia and large referred pain areas were found in patients with chronic whiplash syndrome compared to control subjects both within and outside the traumatised area. The ®ndings suggest a generalised central hyperexcitability in patients suffering from chronic whiplash syndrome. This indicates that the pain might be considered as a neurogenic type of pain, and new pharmacological treatments should be investigated accordingly. q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Chronic whiplash syndrome; Muscular hyperalgesia; Experimental muscle pain
1. Introduction The chronic whiplash syndrome has been known for several decades. In Australia, the syndrome is estimated to occur at an incidence rate of 1/1000 (Barnsley et al., 1994), and 14±42% of the patients develops chronic pain. The majority of patients suffering from chronic whiplash syndrome is in the employable age, and hence the syndrome
* Corresponding author. Fax: 145-98-15-4008. E-mail address: [email protected] (T. Graven-Nielsen)
constitutes, apart from the personal suffering, also a substantial socio-economic problem (Barnsley et al. 1994). Previous studies on the whiplash syndrome have mainly been concentrated on outcome measures of the treatment (Deans et al., 1987; Gargan and Bannister, 1994; Jonsson et al., 1994; Radanov et al., 1995) and injury mechanisms (Sturzenegger et al., 1994). The aetiology, or pathogenesis of the syndrome are, however, not fully understood. The pain has been inadequately characterised, and it is still unclear whether it is of neurogic or nociceptive origin. The neurogenic component may be due to nerve damage
0304-3959/99/$20.00 q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. PII: S 0304-395 9(99)00106-2
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or changed central processing of peripheral stimuli whereas the nociceptive component may be due to tissue damage. Ever since chronic whiplash syndrome was ®rst recognised as a disease entity, a pre-morbid psychic constitution has been suggested (Miller, 1961). However, it seems that the anxiety and depression found in whiplash patients are more a consequence of chronic pain than a pre-existing condition (Lee et al., 1993). Muscular structures have been suggested to take a part in whiplash pain. Signs of muscle damage have been found by palpation, such as swelling of the sternomastoid muscles and spasm of the neck and shoulder muscles (Jeffreys, 1980). Ultrasound scanning has revealed post-traumatic lesions in muscles of whiplash patients (Martino et al., 1992). Trigger points and myofacial pain have also been suggested as contributing factors (Fricton, 1993), but a systematic investigation of this hypothesis has not been carried out. The nociceptive barrage from muscles during the injury may cause central hyperexcitability of dorsal horn neurones as seen in animal studies in which myositis gives reason to central hyperexcitability (Hoheisel et al., 1997). Thus central hyperexcitability due to the muscle injury may cause chronic pain after tissue restoration. Intramuscular infusion of hypertonic saline has previously been used to induce experimental local and referred muscle pain in healthy volunteers (Kellgren, 1938; Stohler and Lund, 1994; Graven-Nielsen et al., 1997a,b). Moreover, saline-induced muscle pain has been used to assess the muscular sensibility and the mechanism of referred pain in muscle pain patients. When hypertonic saline was infused into a pain-free muscle, it produced pain with a higher intensity and larger referred pain areas in ®bromyalgia patients compared with control subjects (SoÈrensen et al., 1998). The increased referred pain areas most likely indicate hyperexcitability of central converging neurones (Mense, 1994). The present study assessed muscular sensibility to experimental muscle pain in patients with chronic whiplash pain. The hypothesis is that central hyperexcitability is present in chronic whiplash patients and manifested as increased muscular sensibility and increased referred pain areas to saline-induced muscle pain both within and outside areas involved in the trauma.
2. Materials and methods 2.1. Subjects Eleven patients, four males and seven females, with a mean age of 42 years (range: 28±69 years) were included. The patients had chronic whiplash syndrome and had been referred to the pain clinic at Aalborg Hospital. All patients ful®lled the criteria described in the Quebec Task Force (Spitzer et al., 1995), and all patients had symptoms related to whiplash associated disorder (grade 2). Chronic pain was
de®ned as pain lasting for more than 1 year. Mean duration of pain was 4 years and 5 months (range: 1 year and 1 month±7 years and 5 months). Sex- and age-matched control subjects, 4 males and 7 females, with a mean age of 39 years (range: 26±50 years) with no history of musculoskeletal pain conditions were included. The patient group completed a Danish version of the McGill Pain Questionnaire (Drewes et al., 1993) describing their habitual pain, and they outlined the painful areas on an anatomical map. The experimental assessment was performed on the most affected side (i.e. three left side patients and eight right side patients). The study was performed in accordance with the Declaration of Helsinki and was approved by the local Ethics Committee. Written informed consent was obtained from all participants before inclusion. 2.2. Pressure sensibility A pressure algometer with a stimulation area of 1 cm 2 (Somedic AB, Sweden) was used for assessment. Pressure pain thresholds were measured as the mean of three trials in which the pressure was increased with 30 kPa/s until the subject experienced the pressure as being painful. Pressure pain thresholds were measured over the middle part of the infraspinatus muscle, over the brachioradial muscle just distal to the lateral epicondylus, and over the middle part of the anterior tibial muscle. 2.3. Pin-prick and touch sensibility Pin-prick thresholds were determined by using Von Frey hairs with bending forces ranging from 4.467 mg to 446.7 g in 20 logarithmically increasing steps (Stoelting, USA). The pin-prick threshold was de®ned as the lowest bending force at which the subject experienced a pricking pain sensation. In addition, the skin was stimulated by a cotton swap. The subjects scored the intensity of the cotton swap touch on a visual analogue scale (VAS) where 0 cm indicated `no touch', the middle part of the scale indicated `normal touch', and 10 cm `very unpleasant sensations'. The cutaneous sensibility was assessed over the infraspinatus, brachioradial, and anterior tibial muscles. 2.4. Saline-induced muscle pain Experimental muscle pain was induced in the infraspinatus and anterior tibial muscles. Infusion of hypertonic saline (5.85% given over 20 s) was accomplished by a computercontrolled syringe pump (IVAC, model 770) with a 10 ml plastic syringe (Graven-Nielsen et al., 1997a). A tube (IVAC G30303, extension set with polyethylene inner line) connected the syringe to the stainless disposable needle (27 G, 20 mm). The saline-induced pain intensity was scored on a 10 cm electronic visual analogue scale (VAS) where 0 cm indicated `no pain' and 10 cm `intolerable pain'. The VAS scores were recorded every 5 s by the computer. From the VAS-time pro®le, the area under the curve (VAS
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area), maximum pain (VAS peak), and duration were calculated. After the infusion of saline, the subjects were asked to draw the areas of pain on an anatomical map. The circumference was digitalised (ACECAD D9000 1 digitizer), and the area calculated (Sigma-Scan). The area of pain was given as arbitrary units. Referred pain was de®ned as pain occurring outside and separated from the local pain area. The quality of the saline-induced muscle pain was assessed with a Danish version of the McGill Pain Questionnaire. The words chosen by at least 40% of the subjects were extracted. 2.5. Statistical analysis The data were analysed using the Mann-Whitney rank sum test. Data are presented as mean ^ standard deviations (SD). Statistical signi®cance was de®ned as P , 0:05. 3. Results 3.1. Whiplash pain The patients described their habitual pain as `taut' (82% of patients), `burning' (73%), `exhausting' (73%), `shooting' (64%), `sickening' (55%), `penetrating' (55%), `agonising' (55%), `gruelling' (45%), and `squeezing' (45%). The area of their every day pain was mean 63.1^72.3 arbitrary units (range: 7.89±284.41 a.u.) mainly located around the neck and shoulder region with radiating pain into one of the upper extremities (Fig. 1). Five patients experienced pain that was more widespread. Eight patients had pain in infraspinatus area and six patients has pain in the brachioradial area in which the somatosensory sensibility was assessed. No patients had anterior tibial muscle pain before assessment of the somatosensory sensibility.
Fig. 1. The distribution of on-going pain in the eleven whiplash patients (n 11) before the experimental assessment. The pain areas from all patients are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
3.2. Pin-prick, touch, and pressure sensibility In the patient group, a signi®cant decrease of the pressure pain thresholds was found (P , 0:01) compared with the control subjects in both the infraspinatus, brachioradial, and anterior tibial muscle (Table 1). No differences were found in pin-prick thresholds and VAS for cotton swap (Table 1).
Table 1 Somatosensory sensibility a
Pressure pain thresholds (kPa) Infraspinatus muscle Brachioradial muscle Anterior tibial muscle Pin-prick thresholds Infraspinatus area Brachioradial area Anterior tibial area VAS scores for cotton swap (cm) Infraspinatus area Brachioradial area Anterior tibial area
Control subjects
Whiplash patients
P-value
492.8 ^ 184.8 363.8 ^ 130.4 497.8 ^ 149.1
152.2 ^ 84.9 70.0 ^ 53.4 172.7 ^ 80.0
0.01 0.01 0.01
12.4 ^ 1.1 12.4 ^ 1.5 12.9 ^ 1.4
11.5 ^ 2.5 10.7 ^ 3.2 11.8 ^ 1.7
NS NS NS
5.3 ^ 0.4 5.2 ^ 0.4 5.1 ^ 0.3
5.2 ^ 0.9 6.3 ^ 1.5 4.4 1 1.2
NS NS NS
a Mean (^SD, n 11) pressure pain thresholds, pin-prick thresholds, and VAS scores for cotton swap. P-values are from the Mann±Whitney test. NS, nonsigni®cant.
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Table 2 VAS parameters a
Infraspinatus muscle VAS area (cm s) VAS peak(cm) VAS onset (s) VAS duration (s) Anterior tibial muscle VAS area (cm s) VAS peak(cm) VAS onset (s) VAS duration (s)
Control subjects
Whiplash patients
P-value
780.5 ^ 366.3 5.2 ^ 1.8 35.5 ^ 5.0 317.7 ^ 115.4
4138.1 ^ 1707.2 8.7 ^ 1.5 22.7 ^ 6.5 719.5 ^ 244.8
0.01 0.01 NS 0.01
978.7 ^ 536.4 4.7 ^ 2.0 23.2 ^ 16.4 306.4 ^ 81.2
4370.8 ^ 2578.1 8.9 ^ 1.9 25.9 ^ 30.2 723.6 ^ 303.6
0.01 0.01 NS 0.01
a
Mean (^SD, n 11) VAS parameters determined after infusion of hypertonic saline into the infraspinatus and anterior tibial muscle. The infusions were performed on the right side for control subjects and on the painful side for patients. P-values are from the Mann±Whitney test. NS, non-signi®cant.
3.3. Saline-induced muscle pain The patient group experienced signi®cantly more intense
Fig. 3. The distribution of saline-induced muscle pain after infusion into the tibialis anterior muscle in whiplash patients and control subjects (n 11). In control subjects, the infusions were given into the right side whereas the most affected side was tested in the patients, (i.e. three left side patients and eight right side patients). The pain areas from all patients/ controls are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
Fig. 2. The distribution of saline-induced muscle pain after infusion into the infraspinatus muscle in whiplash patients and control subjects (n 11). In control subjects, the infusions were given into the right side whereas the most affected side was tested in the patients (i.e. three left side patients and eight right side patients). The pain areas from all patients/controls are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
pain than the control subjects measured by increased (P , 0:01) VAS areas, VAS peaks, and duration (Table 2). This was seen after infusion of hypertonic saline into both the infraspinatus and the anterior tibial muscle. The offset of pain was prolonged compared with the control subjects (P , 0:01). Onset of pain was similar in the two groups (Table 2). Infusion of hypertonic saline into the infraspinatus muscle caused pain areas that were signi®cantly larger in patients than in control subjects (Fig. 2, 22.2 ^ 9.9 vs. 2.6 ^ 4.3 arbitrary units, P , 0:01). Similar results were obtained after infusion into the anterior tibial muscle (Fig. 3, 13.5 ^ 15.9 vs. 1.4^1.1 arbitrary units, P , 0:01). The distribution of pain was different between control subjects and patients. In control subjects, the spread of the pain was typically distal to the infusion site, whereas whiplash patients experienced both distally and proximally referred pain. This was seen after infusion of hypertonic saline into the infraspinatus and anterior tibial muscle. After infusion of hypertonic saline into the infraspinatus muscle, the words most frequently used by the patients to describe the pain were: `taut' (55% of the patients), `shoot-
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ing' (45%), `tiring' (45%), `cruel' (45%), and `intense' (45%). In contrast, the control subjects only selected `taut' (55% of control subjects). To describe the saline-induced pain in the anterior tibial muscle, the patients selected the words `taut' (73%), `scalding' (64%), `sharp' (45%), `exhausting' (45%), and `wretched' (45%). The control subjects chose the word `dull' (55%) to describe salineinduced pain in the anterior tibial muscle. 4. Discussion In the present study, we have found muscular hyperalgesia to painful muscle stimulation not only in the neck and shoulder region, but also in distant areas in which the patient does not normally experience pain. This ®nding could be a manifestation of a generalised central hyperexcitability and support the hypothesis that central pathogenetic mechanisms are involved in the whiplash syndrome. Widespread hyperalgesia to intramuscular electrical stimulation has been found in ®bromyalgia and myofacial pain patients with signi®cantly lower pain thresholds in painful and non-painful areas (Vecchiet et al., 1994). Moreover, decreased sensibility to pressure stimulation of the ®nger has been found in tension-type headache patients compared with control subjects (Bendtsen et al., 1996). Similar ®ndings of increased muscular sensibility to saline-induced muscle pain in muscles without habitual pain are reported in ®bromyalgia patients compared with control subjects (SoÈrensen et al., 1998). Moreover, the pain in ®bromyalgia patients was more ef®ciently treated with NMDA-antagonist (ketamine) compared with conventional morphine and lidocaine management. This also indicates a role of central hyperexcitability in this patient group (SoÈrensen et al., 1995, 1997; Welin and Rabow, 1998). Whiplash patients reported not only referred pain in areas distal to the stimulated muscle, but also frequently described referred pain in proximal areas. The experimental muscle pain model used in the present study has previously been used with healthy volunteers, and typically the referred pain is spread to distal areas (Graven-Nielsen et al., 1997a,b). In contrast, the whiplash patients in the present study and the ®bromyalgia patients (SoÈrensen et al., 1998) very often have proximally referred pain areas evoked by saline-induced muscle pain. In animal studies, expansion of receptive ®elds to areas proximal to the normal receptive ®eld has been found as a manifestation of central hyperexcitability (Cook et al., 1987; Hoheisel et al., 1997). Mense (1993) proposed that muscular hyperalgesia and hyperexcitability of dorsal horn neurones may be induced by various mechanisms: (1) decrease in the ef®cacy of the descending antinociceptive system; (2) central sensitisation due to longlasting activation of receptive ®elds; or (3) heterotopic facilitation caused by active nociceptive ®bres outside the receptive ®elds. In some way, the symptoms of patients suffering from
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chronic whiplash pain are similar to the symptoms of patients with ®bromyalgia. Magnusson (1994) has investigated 38 whiplash patients and found that 10.4% had symptoms corresponding to the diagnosis of ®bromyalgia. Helme et al. (1987) found that the neurogenic ¯are response was increased in patients with chronic pain syndromes, such as ®brositis syndrome, whiplash syndrome, low back pain syndrome, and regional pain syndrome compared with control subjects. Patients with these syndromes are characterised by the presence of tender points in predictable anatomical locations (Helme et al., 1987). It is not clear how central hyperexcitability is maintained and eventually causes chronicity, but most likely an ongoing nociceptive afferent barrage is needed. A possible explanation could be that the whiplash trauma causes tissue injury and possibly in some cases minor nerve injuries not easily detectable. These injuries could lead to an increased neural activity at the site of the injury resulting in the release of excitatory amino acids and neuropeptides, which can lead to hyperexcitability dorsal horn cells. Excessive depolarisation of dorsal horn neurones may cause excitotoxicity, subsequent cell dysfunction, and loss of inhibition (Dubner et al., 1993). Whether this explanatory model is valid in chronic whiplash pain is still hypothetical. 5. Conclusion The present study suggests the existence of a central hyperexcitability as an important mechanism involved in chronic whiplash pain because the somatosensory sensibility and referred pain mechanism were facilitated in areas distant to the tissue involved in the whiplash injury. The implications of the present study might be an investigation of new treatment regimes. Acknowledgements This study was supported by The Danish National Research Foundation. References Barnsley L, Lord S, Bogduk N. Whiplash injury. Pain 1994;58:283±307. Bendtsen L, Jensen R, Olesen J. Decreased pain detection and tolerance thresholds in chronic tension-type headache. Arch Neurol 1996;53:373±376. Cook AJ, Woolf CJ, Wall PD, McMahon SB. Dynamic receptive ®eld plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 1987;325:151±153. Deans GT, Magalliard JN, Kerr M, Rutherford WH. Neck sprain±a major cause of disability following car accidents. Injury 1987;118:10±12. Drewes AM, Helweg-Larsen S, Petersen P, Brennum J, Andreasen A, Poulsen LH, Jensen TS. McGill Pain Questionnaire translated into Danish: experimental and clinical ®ndings. Clin J Pain 1993;9:80±87. Dubner R. Spinal cord neuronal plasticity: mechanisms of persistent pain following tissue damage and nerve injury. In: Vecchiet L, Albe-Fessard
234
M. Koelbaek Johansen et al. / Pain 83 (1999) 229±234
D, Lindblom U, Giamberardino MA, editors. New trends in referred pain and hyperalgesia, Amsterdam: Elsevier, 1993. pp. 109±117. Fricton JR. Myofacial pain and whiplash. Spine, State of the Art Rev 1993;7:403±422. Gargan MF, Bannister GC. The rate of recovery following whiplash injury. Eur Spine J 1994;3:162±164. Graven-Nielsen T, Arendt-Nielsen L, Svensson P, Jensen TS. Quanti®cation of local and referred muscle pain in humans after sequential i.m. injections of hypertonic saline. Pain 1997a;69:111±117. Graven-Nielsen T, Arendt-Nielsen L, Svensson P, Jensen TS. Stimulusresponse functions in areas with experimentally induced referred muscle pain - a psychophysical study. Brain Res 1997b;744:121±128. Helme RD, Littlejohn GO, Weinstein C. Neurogenic ¯are responses in chronic rheumatic pain syndromes. Clin Exp Neurol 1987;23:91±94. Hoheisel U, Sander B, Mense S. Myositis-induced functional reorganisation of the rat dorsal horn: effects of spinal superfusion with antagonists to neurokinin and glutamate receptors. Pain 1997;69:219±230. Jeffreys E. Soft tissue injuries of the cervical spine, disorders of the cervical spine. London: Butterworth, 1980. pp. 81-89. Jonsson Jr H, Cesarini K, Sahlstedt B, Rauschning W. Findings and outcome in whiplash-type neck distortions. Spine 1994;19:2733±2743. Kellgren JH. Observations on referred pain arising from muscle. Clin Sci 1938;3:175±190. Lee J, Giles K, Drummond PD. Psychological disturbances and an exaggerated response to pain in patients with whiplash injury. J Psychosom Res 1993;37:105±110. Magnusson T. Extracervical symptoms after whiplash trauma. Cephalalgia 1994;14:223±227. Martino F, Ettorre GC, Cafaro E, Macarini L, Bancale R, Sion E. LeÂcographia musculo-tendinea nei traumi distorvi acuti del collo. Radiol Med (Torino) 1992;83:211±215. Mense S. Spinal mechanisms of muscle pain and hyperalgesia. In: Vecchiet L, AlbeFessard D, Lindblom U, Giamberardino MA, editors. New trends in referred pain and hyperalgesia. Amsterdam: Elsevier, 1993. pp. 25±34. Mense S. Referral of muscle pain. New aspects. APS 1994;3:1±9.
Miller H. Accident neurosis. Br Med J 1961;1:992±998. Radanov BP, Sturzenegger M, Di Stefano G. Long-term outcome after whiplash injury. A 2-year follow-up considering features of injury mechanism and somatic, radiologic, and psychosocial ®ndings. Medicine (Baltimore) 1995;74:281±297. SoÈrensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with ®bromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol 1995;24:360±365. SoÈrensen J, Bengtsson A, Ahlner J, Henriksson KG, Ekselius L, Bengtsson M. Fibromyalgia - are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol 1997;24:1615±1621. SoÈrensen J, Graven-Nielsen T, Henriksson KG, Bengtsson M, Arendt-Nielsen L. Hyperexcitability in ®bromyalgia. J Rheumatol 1998;25:152± 155. Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. Scienti®c monograph of the Quebec Task Force on WhiplashAssociated Disorders: rede®ning `whiplash' and its management. Spine, Suppl 1995;20:1±73. Stohler CS, Lund JP. Effects of noxious stimulation of the jaw muscles on the sensory experience of volunteer human subjects. In: Stohler CS, Carlson DS, editors. Biological and pyschological aspects of orofacial pain, center for human growth and development. Ann Arbor, MI: The University of Michigan, 1994. pp. 55±73. Sturzenegger M, DiStefano G, Radanov BP, Schnidrig A. Presenting symptoms and signs after whiplash injury: the in¯uence of accident mechanisms. Neurology 1994;44:688±693. Vecchiet L, Giamberardino MA, Bigontina P, Dragani L. Comparative sensory evaluation of parietal tissues in painful and nonpainful areas in ®bromyalgia and myofacial pain syndrome. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th world congress on pain. Progress in pain and management. Seattle, WA: IASP Press, 1994. pp. 177±185. Welin M, Rabow S. Pharmacological pain analysis in patients with ®bromyalgia. J Musculoskel Pain 1998;6:140 abstract.
Generalised muscular hyperalgesia in chronic whiplash syndrome Mona Koelbaek Johansen a, Thomas Graven-Nielsen b,*, Anders Schou Olesen c, Lars Arendt-Nielsen b b
a Department of Rheumatology, Aalborg Hospital, Aalborg, Denmark Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Fredrik Bajers Vej 7D-3, DK9220 Aalborg E, Denmark c The Pain Clinic, Aalborg Hospital, Aalborg, Denmark
Received 10 December 1998; received in revised form 31 March 1999; accepted 21 May 1999
Abstract The whiplash syndrome has immense socio-economic impact. Despite extensive studies over the past years, the mechanisms involved in maintaining the pain in chronic whiplash patients are poorly understood. The aim of the present experimental study was to examine the muscular sensibility in areas within and outside the region involved in the whiplash trauma. Eleven chronic whiplash patients and 11 sex and age matched control subjects were included in the study. Before the experiment, the whiplash patients had pain in the neck and shoulder region with radiating pain to the arm. Five patients reported pain that was more widespread. The somatosensory sensibility in the areas over the infraspinatus, brachioradial, and anterior tibial muscles was assessed by pressure stimulation, pin-prick stimulation, and cotton swap stimulation. Infusion of hypertonic saline (5.85%, 0.5 ml) into the infraspinatus and anterior tibial muscles was performed to assess the muscular sensibility and referred pain pattern. The saline-induced muscle pain intensity was assessed on a continuous visual analogue scale (VAS). The distribution of pain was drawn on an anatomical map. The pressure pain thresholds were signi®cantly lower in patients (P , 0:01) compared with controls: infraspinatus (mean 152.2 vs. 172.7 kPa), brachioradial (mean 70.0 vs. 363.8 kPa), and anterior tibial muscle (mean 172.7 vs. 497.8 kPa). The skin sensibility to pin-prick stimulation and cotton swap stimulation was not different between patients and controls. Infusion of hypertonic saline caused signi®cantly higher VAS scores with longer duration in patients compared to control subjects (P , 0:01). The area under the VAS-time curve was signi®cantly (P , 0:01) increased in patients compared to control subjects after injection into the infraspinatus muscle (mean 4138.1 vs. 780.0 cm s) and anterior tibial muscle (mean 4370.8 vs. 978.7 cm s). The saline infusion caused local pain de®ned as pain located around the injection site and referred pain areas not included in the local pain area. The area of local and referred pain were signi®cantly larger in patients compared to control subjects (P , 0:01). In the control group, the referred pain areas to infusion of hypertonic saline into the anterior tibial muscle were found at the dorsal aspect of the ankle. In contrast, the areas of referred pain were quite widespread in the patient group with both distal and proximal referred pain areas. In the present study, muscular hyperalgesia and large referred pain areas were found in patients with chronic whiplash syndrome compared to control subjects both within and outside the traumatised area. The ®ndings suggest a generalised central hyperexcitability in patients suffering from chronic whiplash syndrome. This indicates that the pain might be considered as a neurogenic type of pain, and new pharmacological treatments should be investigated accordingly. q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Chronic whiplash syndrome; Muscular hyperalgesia; Experimental muscle pain
1. Introduction The chronic whiplash syndrome has been known for several decades. In Australia, the syndrome is estimated to occur at an incidence rate of 1/1000 (Barnsley et al., 1994), and 14±42% of the patients develops chronic pain. The majority of patients suffering from chronic whiplash syndrome is in the employable age, and hence the syndrome
* Corresponding author. Fax: 145-98-15-4008. E-mail address: [email protected] (T. Graven-Nielsen)
constitutes, apart from the personal suffering, also a substantial socio-economic problem (Barnsley et al. 1994). Previous studies on the whiplash syndrome have mainly been concentrated on outcome measures of the treatment (Deans et al., 1987; Gargan and Bannister, 1994; Jonsson et al., 1994; Radanov et al., 1995) and injury mechanisms (Sturzenegger et al., 1994). The aetiology, or pathogenesis of the syndrome are, however, not fully understood. The pain has been inadequately characterised, and it is still unclear whether it is of neurogic or nociceptive origin. The neurogenic component may be due to nerve damage
0304-3959/99/$20.00 q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. PII: S 0304-395 9(99)00106-2
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or changed central processing of peripheral stimuli whereas the nociceptive component may be due to tissue damage. Ever since chronic whiplash syndrome was ®rst recognised as a disease entity, a pre-morbid psychic constitution has been suggested (Miller, 1961). However, it seems that the anxiety and depression found in whiplash patients are more a consequence of chronic pain than a pre-existing condition (Lee et al., 1993). Muscular structures have been suggested to take a part in whiplash pain. Signs of muscle damage have been found by palpation, such as swelling of the sternomastoid muscles and spasm of the neck and shoulder muscles (Jeffreys, 1980). Ultrasound scanning has revealed post-traumatic lesions in muscles of whiplash patients (Martino et al., 1992). Trigger points and myofacial pain have also been suggested as contributing factors (Fricton, 1993), but a systematic investigation of this hypothesis has not been carried out. The nociceptive barrage from muscles during the injury may cause central hyperexcitability of dorsal horn neurones as seen in animal studies in which myositis gives reason to central hyperexcitability (Hoheisel et al., 1997). Thus central hyperexcitability due to the muscle injury may cause chronic pain after tissue restoration. Intramuscular infusion of hypertonic saline has previously been used to induce experimental local and referred muscle pain in healthy volunteers (Kellgren, 1938; Stohler and Lund, 1994; Graven-Nielsen et al., 1997a,b). Moreover, saline-induced muscle pain has been used to assess the muscular sensibility and the mechanism of referred pain in muscle pain patients. When hypertonic saline was infused into a pain-free muscle, it produced pain with a higher intensity and larger referred pain areas in ®bromyalgia patients compared with control subjects (SoÈrensen et al., 1998). The increased referred pain areas most likely indicate hyperexcitability of central converging neurones (Mense, 1994). The present study assessed muscular sensibility to experimental muscle pain in patients with chronic whiplash pain. The hypothesis is that central hyperexcitability is present in chronic whiplash patients and manifested as increased muscular sensibility and increased referred pain areas to saline-induced muscle pain both within and outside areas involved in the trauma.
2. Materials and methods 2.1. Subjects Eleven patients, four males and seven females, with a mean age of 42 years (range: 28±69 years) were included. The patients had chronic whiplash syndrome and had been referred to the pain clinic at Aalborg Hospital. All patients ful®lled the criteria described in the Quebec Task Force (Spitzer et al., 1995), and all patients had symptoms related to whiplash associated disorder (grade 2). Chronic pain was
de®ned as pain lasting for more than 1 year. Mean duration of pain was 4 years and 5 months (range: 1 year and 1 month±7 years and 5 months). Sex- and age-matched control subjects, 4 males and 7 females, with a mean age of 39 years (range: 26±50 years) with no history of musculoskeletal pain conditions were included. The patient group completed a Danish version of the McGill Pain Questionnaire (Drewes et al., 1993) describing their habitual pain, and they outlined the painful areas on an anatomical map. The experimental assessment was performed on the most affected side (i.e. three left side patients and eight right side patients). The study was performed in accordance with the Declaration of Helsinki and was approved by the local Ethics Committee. Written informed consent was obtained from all participants before inclusion. 2.2. Pressure sensibility A pressure algometer with a stimulation area of 1 cm 2 (Somedic AB, Sweden) was used for assessment. Pressure pain thresholds were measured as the mean of three trials in which the pressure was increased with 30 kPa/s until the subject experienced the pressure as being painful. Pressure pain thresholds were measured over the middle part of the infraspinatus muscle, over the brachioradial muscle just distal to the lateral epicondylus, and over the middle part of the anterior tibial muscle. 2.3. Pin-prick and touch sensibility Pin-prick thresholds were determined by using Von Frey hairs with bending forces ranging from 4.467 mg to 446.7 g in 20 logarithmically increasing steps (Stoelting, USA). The pin-prick threshold was de®ned as the lowest bending force at which the subject experienced a pricking pain sensation. In addition, the skin was stimulated by a cotton swap. The subjects scored the intensity of the cotton swap touch on a visual analogue scale (VAS) where 0 cm indicated `no touch', the middle part of the scale indicated `normal touch', and 10 cm `very unpleasant sensations'. The cutaneous sensibility was assessed over the infraspinatus, brachioradial, and anterior tibial muscles. 2.4. Saline-induced muscle pain Experimental muscle pain was induced in the infraspinatus and anterior tibial muscles. Infusion of hypertonic saline (5.85% given over 20 s) was accomplished by a computercontrolled syringe pump (IVAC, model 770) with a 10 ml plastic syringe (Graven-Nielsen et al., 1997a). A tube (IVAC G30303, extension set with polyethylene inner line) connected the syringe to the stainless disposable needle (27 G, 20 mm). The saline-induced pain intensity was scored on a 10 cm electronic visual analogue scale (VAS) where 0 cm indicated `no pain' and 10 cm `intolerable pain'. The VAS scores were recorded every 5 s by the computer. From the VAS-time pro®le, the area under the curve (VAS
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area), maximum pain (VAS peak), and duration were calculated. After the infusion of saline, the subjects were asked to draw the areas of pain on an anatomical map. The circumference was digitalised (ACECAD D9000 1 digitizer), and the area calculated (Sigma-Scan). The area of pain was given as arbitrary units. Referred pain was de®ned as pain occurring outside and separated from the local pain area. The quality of the saline-induced muscle pain was assessed with a Danish version of the McGill Pain Questionnaire. The words chosen by at least 40% of the subjects were extracted. 2.5. Statistical analysis The data were analysed using the Mann-Whitney rank sum test. Data are presented as mean ^ standard deviations (SD). Statistical signi®cance was de®ned as P , 0:05. 3. Results 3.1. Whiplash pain The patients described their habitual pain as `taut' (82% of patients), `burning' (73%), `exhausting' (73%), `shooting' (64%), `sickening' (55%), `penetrating' (55%), `agonising' (55%), `gruelling' (45%), and `squeezing' (45%). The area of their every day pain was mean 63.1^72.3 arbitrary units (range: 7.89±284.41 a.u.) mainly located around the neck and shoulder region with radiating pain into one of the upper extremities (Fig. 1). Five patients experienced pain that was more widespread. Eight patients had pain in infraspinatus area and six patients has pain in the brachioradial area in which the somatosensory sensibility was assessed. No patients had anterior tibial muscle pain before assessment of the somatosensory sensibility.
Fig. 1. The distribution of on-going pain in the eleven whiplash patients (n 11) before the experimental assessment. The pain areas from all patients are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
3.2. Pin-prick, touch, and pressure sensibility In the patient group, a signi®cant decrease of the pressure pain thresholds was found (P , 0:01) compared with the control subjects in both the infraspinatus, brachioradial, and anterior tibial muscle (Table 1). No differences were found in pin-prick thresholds and VAS for cotton swap (Table 1).
Table 1 Somatosensory sensibility a
Pressure pain thresholds (kPa) Infraspinatus muscle Brachioradial muscle Anterior tibial muscle Pin-prick thresholds Infraspinatus area Brachioradial area Anterior tibial area VAS scores for cotton swap (cm) Infraspinatus area Brachioradial area Anterior tibial area
Control subjects
Whiplash patients
P-value
492.8 ^ 184.8 363.8 ^ 130.4 497.8 ^ 149.1
152.2 ^ 84.9 70.0 ^ 53.4 172.7 ^ 80.0
0.01 0.01 0.01
12.4 ^ 1.1 12.4 ^ 1.5 12.9 ^ 1.4
11.5 ^ 2.5 10.7 ^ 3.2 11.8 ^ 1.7
NS NS NS
5.3 ^ 0.4 5.2 ^ 0.4 5.1 ^ 0.3
5.2 ^ 0.9 6.3 ^ 1.5 4.4 1 1.2
NS NS NS
a Mean (^SD, n 11) pressure pain thresholds, pin-prick thresholds, and VAS scores for cotton swap. P-values are from the Mann±Whitney test. NS, nonsigni®cant.
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Table 2 VAS parameters a
Infraspinatus muscle VAS area (cm s) VAS peak(cm) VAS onset (s) VAS duration (s) Anterior tibial muscle VAS area (cm s) VAS peak(cm) VAS onset (s) VAS duration (s)
Control subjects
Whiplash patients
P-value
780.5 ^ 366.3 5.2 ^ 1.8 35.5 ^ 5.0 317.7 ^ 115.4
4138.1 ^ 1707.2 8.7 ^ 1.5 22.7 ^ 6.5 719.5 ^ 244.8
0.01 0.01 NS 0.01
978.7 ^ 536.4 4.7 ^ 2.0 23.2 ^ 16.4 306.4 ^ 81.2
4370.8 ^ 2578.1 8.9 ^ 1.9 25.9 ^ 30.2 723.6 ^ 303.6
0.01 0.01 NS 0.01
a
Mean (^SD, n 11) VAS parameters determined after infusion of hypertonic saline into the infraspinatus and anterior tibial muscle. The infusions were performed on the right side for control subjects and on the painful side for patients. P-values are from the Mann±Whitney test. NS, non-signi®cant.
3.3. Saline-induced muscle pain The patient group experienced signi®cantly more intense
Fig. 3. The distribution of saline-induced muscle pain after infusion into the tibialis anterior muscle in whiplash patients and control subjects (n 11). In control subjects, the infusions were given into the right side whereas the most affected side was tested in the patients, (i.e. three left side patients and eight right side patients). The pain areas from all patients/ controls are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
Fig. 2. The distribution of saline-induced muscle pain after infusion into the infraspinatus muscle in whiplash patients and control subjects (n 11). In control subjects, the infusions were given into the right side whereas the most affected side was tested in the patients (i.e. three left side patients and eight right side patients). The pain areas from all patients/controls are superimposed (i.e. common pain areas are more dark than the pain areas selected by only a few patients).
pain than the control subjects measured by increased (P , 0:01) VAS areas, VAS peaks, and duration (Table 2). This was seen after infusion of hypertonic saline into both the infraspinatus and the anterior tibial muscle. The offset of pain was prolonged compared with the control subjects (P , 0:01). Onset of pain was similar in the two groups (Table 2). Infusion of hypertonic saline into the infraspinatus muscle caused pain areas that were signi®cantly larger in patients than in control subjects (Fig. 2, 22.2 ^ 9.9 vs. 2.6 ^ 4.3 arbitrary units, P , 0:01). Similar results were obtained after infusion into the anterior tibial muscle (Fig. 3, 13.5 ^ 15.9 vs. 1.4^1.1 arbitrary units, P , 0:01). The distribution of pain was different between control subjects and patients. In control subjects, the spread of the pain was typically distal to the infusion site, whereas whiplash patients experienced both distally and proximally referred pain. This was seen after infusion of hypertonic saline into the infraspinatus and anterior tibial muscle. After infusion of hypertonic saline into the infraspinatus muscle, the words most frequently used by the patients to describe the pain were: `taut' (55% of the patients), `shoot-
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ing' (45%), `tiring' (45%), `cruel' (45%), and `intense' (45%). In contrast, the control subjects only selected `taut' (55% of control subjects). To describe the saline-induced pain in the anterior tibial muscle, the patients selected the words `taut' (73%), `scalding' (64%), `sharp' (45%), `exhausting' (45%), and `wretched' (45%). The control subjects chose the word `dull' (55%) to describe salineinduced pain in the anterior tibial muscle. 4. Discussion In the present study, we have found muscular hyperalgesia to painful muscle stimulation not only in the neck and shoulder region, but also in distant areas in which the patient does not normally experience pain. This ®nding could be a manifestation of a generalised central hyperexcitability and support the hypothesis that central pathogenetic mechanisms are involved in the whiplash syndrome. Widespread hyperalgesia to intramuscular electrical stimulation has been found in ®bromyalgia and myofacial pain patients with signi®cantly lower pain thresholds in painful and non-painful areas (Vecchiet et al., 1994). Moreover, decreased sensibility to pressure stimulation of the ®nger has been found in tension-type headache patients compared with control subjects (Bendtsen et al., 1996). Similar ®ndings of increased muscular sensibility to saline-induced muscle pain in muscles without habitual pain are reported in ®bromyalgia patients compared with control subjects (SoÈrensen et al., 1998). Moreover, the pain in ®bromyalgia patients was more ef®ciently treated with NMDA-antagonist (ketamine) compared with conventional morphine and lidocaine management. This also indicates a role of central hyperexcitability in this patient group (SoÈrensen et al., 1995, 1997; Welin and Rabow, 1998). Whiplash patients reported not only referred pain in areas distal to the stimulated muscle, but also frequently described referred pain in proximal areas. The experimental muscle pain model used in the present study has previously been used with healthy volunteers, and typically the referred pain is spread to distal areas (Graven-Nielsen et al., 1997a,b). In contrast, the whiplash patients in the present study and the ®bromyalgia patients (SoÈrensen et al., 1998) very often have proximally referred pain areas evoked by saline-induced muscle pain. In animal studies, expansion of receptive ®elds to areas proximal to the normal receptive ®eld has been found as a manifestation of central hyperexcitability (Cook et al., 1987; Hoheisel et al., 1997). Mense (1993) proposed that muscular hyperalgesia and hyperexcitability of dorsal horn neurones may be induced by various mechanisms: (1) decrease in the ef®cacy of the descending antinociceptive system; (2) central sensitisation due to longlasting activation of receptive ®elds; or (3) heterotopic facilitation caused by active nociceptive ®bres outside the receptive ®elds. In some way, the symptoms of patients suffering from
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chronic whiplash pain are similar to the symptoms of patients with ®bromyalgia. Magnusson (1994) has investigated 38 whiplash patients and found that 10.4% had symptoms corresponding to the diagnosis of ®bromyalgia. Helme et al. (1987) found that the neurogenic ¯are response was increased in patients with chronic pain syndromes, such as ®brositis syndrome, whiplash syndrome, low back pain syndrome, and regional pain syndrome compared with control subjects. Patients with these syndromes are characterised by the presence of tender points in predictable anatomical locations (Helme et al., 1987). It is not clear how central hyperexcitability is maintained and eventually causes chronicity, but most likely an ongoing nociceptive afferent barrage is needed. A possible explanation could be that the whiplash trauma causes tissue injury and possibly in some cases minor nerve injuries not easily detectable. These injuries could lead to an increased neural activity at the site of the injury resulting in the release of excitatory amino acids and neuropeptides, which can lead to hyperexcitability dorsal horn cells. Excessive depolarisation of dorsal horn neurones may cause excitotoxicity, subsequent cell dysfunction, and loss of inhibition (Dubner et al., 1993). Whether this explanatory model is valid in chronic whiplash pain is still hypothetical. 5. Conclusion The present study suggests the existence of a central hyperexcitability as an important mechanism involved in chronic whiplash pain because the somatosensory sensibility and referred pain mechanism were facilitated in areas distant to the tissue involved in the whiplash injury. The implications of the present study might be an investigation of new treatment regimes. Acknowledgements This study was supported by The Danish National Research Foundation. References Barnsley L, Lord S, Bogduk N. Whiplash injury. Pain 1994;58:283±307. Bendtsen L, Jensen R, Olesen J. Decreased pain detection and tolerance thresholds in chronic tension-type headache. Arch Neurol 1996;53:373±376. Cook AJ, Woolf CJ, Wall PD, McMahon SB. Dynamic receptive ®eld plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 1987;325:151±153. Deans GT, Magalliard JN, Kerr M, Rutherford WH. Neck sprain±a major cause of disability following car accidents. Injury 1987;118:10±12. Drewes AM, Helweg-Larsen S, Petersen P, Brennum J, Andreasen A, Poulsen LH, Jensen TS. McGill Pain Questionnaire translated into Danish: experimental and clinical ®ndings. Clin J Pain 1993;9:80±87. Dubner R. Spinal cord neuronal plasticity: mechanisms of persistent pain following tissue damage and nerve injury. In: Vecchiet L, Albe-Fessard
234
M. Koelbaek Johansen et al. / Pain 83 (1999) 229±234
D, Lindblom U, Giamberardino MA, editors. New trends in referred pain and hyperalgesia, Amsterdam: Elsevier, 1993. pp. 109±117. Fricton JR. Myofacial pain and whiplash. Spine, State of the Art Rev 1993;7:403±422. Gargan MF, Bannister GC. The rate of recovery following whiplash injury. Eur Spine J 1994;3:162±164. Graven-Nielsen T, Arendt-Nielsen L, Svensson P, Jensen TS. Quanti®cation of local and referred muscle pain in humans after sequential i.m. injections of hypertonic saline. Pain 1997a;69:111±117. Graven-Nielsen T, Arendt-Nielsen L, Svensson P, Jensen TS. Stimulusresponse functions in areas with experimentally induced referred muscle pain - a psychophysical study. Brain Res 1997b;744:121±128. Helme RD, Littlejohn GO, Weinstein C. Neurogenic ¯are responses in chronic rheumatic pain syndromes. Clin Exp Neurol 1987;23:91±94. Hoheisel U, Sander B, Mense S. Myositis-induced functional reorganisation of the rat dorsal horn: effects of spinal superfusion with antagonists to neurokinin and glutamate receptors. Pain 1997;69:219±230. Jeffreys E. Soft tissue injuries of the cervical spine, disorders of the cervical spine. London: Butterworth, 1980. pp. 81-89. Jonsson Jr H, Cesarini K, Sahlstedt B, Rauschning W. Findings and outcome in whiplash-type neck distortions. Spine 1994;19:2733±2743. Kellgren JH. Observations on referred pain arising from muscle. Clin Sci 1938;3:175±190. Lee J, Giles K, Drummond PD. Psychological disturbances and an exaggerated response to pain in patients with whiplash injury. J Psychosom Res 1993;37:105±110. Magnusson T. Extracervical symptoms after whiplash trauma. Cephalalgia 1994;14:223±227. Martino F, Ettorre GC, Cafaro E, Macarini L, Bancale R, Sion E. LeÂcographia musculo-tendinea nei traumi distorvi acuti del collo. Radiol Med (Torino) 1992;83:211±215. Mense S. Spinal mechanisms of muscle pain and hyperalgesia. In: Vecchiet L, AlbeFessard D, Lindblom U, Giamberardino MA, editors. New trends in referred pain and hyperalgesia. Amsterdam: Elsevier, 1993. pp. 25±34. Mense S. Referral of muscle pain. New aspects. APS 1994;3:1±9.
Miller H. Accident neurosis. Br Med J 1961;1:992±998. Radanov BP, Sturzenegger M, Di Stefano G. Long-term outcome after whiplash injury. A 2-year follow-up considering features of injury mechanism and somatic, radiologic, and psychosocial ®ndings. Medicine (Baltimore) 1995;74:281±297. SoÈrensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with ®bromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol 1995;24:360±365. SoÈrensen J, Bengtsson A, Ahlner J, Henriksson KG, Ekselius L, Bengtsson M. Fibromyalgia - are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol 1997;24:1615±1621. SoÈrensen J, Graven-Nielsen T, Henriksson KG, Bengtsson M, Arendt-Nielsen L. Hyperexcitability in ®bromyalgia. J Rheumatol 1998;25:152± 155. Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. Scienti®c monograph of the Quebec Task Force on WhiplashAssociated Disorders: rede®ning `whiplash' and its management. Spine, Suppl 1995;20:1±73. Stohler CS, Lund JP. Effects of noxious stimulation of the jaw muscles on the sensory experience of volunteer human subjects. In: Stohler CS, Carlson DS, editors. Biological and pyschological aspects of orofacial pain, center for human growth and development. Ann Arbor, MI: The University of Michigan, 1994. pp. 55±73. Sturzenegger M, DiStefano G, Radanov BP, Schnidrig A. Presenting symptoms and signs after whiplash injury: the in¯uence of accident mechanisms. Neurology 1994;44:688±693. Vecchiet L, Giamberardino MA, Bigontina P, Dragani L. Comparative sensory evaluation of parietal tissues in painful and nonpainful areas in ®bromyalgia and myofacial pain syndrome. In: Gebhart GF, Hammond DL, Jensen TS, editors. Proceedings of the 7th world congress on pain. Progress in pain and management. Seattle, WA: IASP Press, 1994. pp. 177±185. Welin M, Rabow S. Pharmacological pain analysis in patients with ®bromyalgia. J Musculoskel Pain 1998;6:140 abstract.