Clin J Pain. 2001 (Dec); 17 (4): 306–315
Michele Curatolo, M.D., Ph.D., Steen Petersen-Felix, M.D., Ph.D., Lars Arendt-Nielsen, Prof.,
Carmela Giani, M.D., Alex M. Zbinden, M.D., Prof., and Bogdan P. Radanov, M.D., Prof.
Department of Anesthesiology,
University Hospital of Bern,
OBJECTIVE: The mechanisms underlying chronic pain after whiplash injury are usually unclear. Injuries may cause sensitization of spinal cord neurons in animals (central hypersensitivity), which results in increased responsiveness to peripheral stimuli. In humans, the responsiveness of the central nervous system to peripheral stimulation may be explored by applying sensory tests to healthy tissues. The hypotheses of this study were:
(1) chronic whiplash pain is associated with central hypersensitivity;
(2) central hypersensitivity is maintained by nociception arising from the painful or tender muscles in the neck.
DESIGN: Comparison of patients with healthy controls.
SETTING: Pain clinic and laboratory for pain research, university hospital.
PATIENTS: Fourteen patients with chronic neck pain after whiplash injury (car accident) and 14 healthy volunteers.
OUTCOME MEASURES: Pain thresholds to: single electrical stimulus (intramuscular), repeated electrical stimulation (intramuscular and transcutaneous), and heat (transcutaneous). Each threshold was measured at neck and lower limb, before and after local anesthesia of the painful and tender muscles of the neck.
RESULTS: The whiplash group had significantly lower pain thresholds for all tests. except heat, at both neck and lower limb. Local anesthesia of the painful and tender points affected neither intensity of neck pain nor pain thresholds.
CONCLUSIONS: The authors found a hypersensitivity to peripheral stimulation in whiplash patients. Hypersensitivity was observed after cutaneous and muscular stimulation, at both neck and lower limb. Because hypersensitivity was observed in healthy tissues, it resulted from alterations in the central processing of sensory stimuli (central hypersensitivity). Central hypersensitivity was not dependent on a nociceptive input arising from the painful and tender muscles.
From the FULL TEXT Article:
Whiplash injury results in chronic neck pain and headache
in about 20% of subjects. [1, 2] This pain syndrome
frequently causes reduced work capacity and conflicts
with insurance companies, and therefore represents a major
socioeconomic problem. 
The mechanisms underlying whiplash pain are unclear.
The limited understanding of the mechanisms involved
in whiplash pain is an important factor preventing
the development of effective therapeutic strategies. 
In animal preparations, injuries may cause sensitization
of spinal cord neurons, which results in increased
sensitivity to noxious stimuli and pain after innocuous
stimuli (central hypersensitivity).  In recent years, central
hypersensitivity has been extensively investigated in
animals, but there is no strong evidence for its presence
in pain conditions in humans.  The literature on central
hypersensitivity after whiplash injury is sparse. In 2 recent
investigations, hyperalgesia has been observed outside
the traumatized area; [5, 6] this suggests that central
mechanisms may be involved in the hyperalgesia.  Because
of the strong discrepancy between the availability
of animal and human data, there is a need for studies
investigating central hypersensitivity in patients.
Experimental studies in healthy volunteers suggest
that ongoing nociceptive input from the periphery may 
or may not  contribute to maintaining central hypersensitivity.
In patients with complex regional pain syndrome,
local anesthesia of painful foci may abolish allodynia
and spontaneous pain.  This suggests that
ongoing nociceptive input from damaged tissues may
maintain central hypersensitivity in complex regional
pain syndrome. There is lack of information on the influence
of ongoing peripheral nociception on central hypersensitivity
in musculoskeletal pain conditions.
In humans, hypersensitivity can be demonstrated when
sensory stimulation evokes pain at stimulus intensities
that do not induce pain in normal subjects. If hypersensitivity
is observed after sensory stimulation of healthy
tissues, its cause must be in the central nervous system.
Moreover, if hypersensitivity is reduced by local anesthesia
of the painful foci, this would indicate that an
ongoing nociceptive afferent input is important for the
maintenance of central hypersensitivity.
The hypotheses of this study were:
(1) chronic pain after whiplash injury is associated with central hypersensitivity; and
(2) central hypersensitivity is maintained by nociception arising from the painful or tender muscles in
These hypotheses were tested by analyzing the
responses to multimodal sensory stimulation [11, 12] in a
group of patients with whiplash pain and in a group of
healthy controls, before and after local anesthesia of the
painful and tender muscles. The sensory stimulation was
applied at both skin and muscle, of both neck (i.e., an
injured area) and lower limb (i.e., a healthy area).
The sample size was calculated based on the test that
we had most frequently used, that is, pain threshold on
transcutaneous repeated electrical stimulation.  We arbitrarily
chose a difference of 2 milliamperes (mA) in the
threshold between the groups as the minimum desired
difference. Setting α = 0.05 and standard deviation = 1.6 mA (observed previously ), and investigating 14
subjects per group, one can detect a significant difference
of 2 mA with a power of β = 0.9 (one-sided hypothesis).
We therefore studied 14 patients with chronic neck
pain after whiplash injury (car accident) and 14 healthy
nonpregnant volunteers. All the subjects were Germanspeaking
Swiss. All the patients were equally covered by
the country insurance plan as previously described.  The
patients were recruited at the Department of Psychiatry
of the University Hospital of Bern. Based on research
experience, the department has established an interdisciplinary
service for the assessment and treatment of whiplash
patients. All consecutive patients who were evaluated
for the first time in the department and fulfilled the
inclusion criteria mentioned further on were enrolled.
The control subjects were recruited by advertisement. Of
the 22 eligible subjects, 14 were chosen to obtain a group
with age and gender distribution as close as possible to
that of the whiplash group.
Whiplash injury was defined as a musculoligamental
strain or sprain of the cervical spine due to hyperextension
and/or hyperflexion, without head-contact injury,
loss of consciousness, post-traumatic amnesia, fractures
or dislocations of the cervical spine.  Exclusion criteria
were the presence of neck pain before the injury, a duration
of neck pain less than 6 months, pregnancy, any
peripheral or central neurologic dysfunction, and coronary
The study was approved by the local ethics committee.
All the subjects gave written informed consent and received
280 Swiss francs for participating in the investigation.
The patients were informed and agreed that the
investigation was performed for research purposes only,
and that the results would not affect diagnosis, treatment,
or legal issues, concerning their pain condition.
The German versions of the NEO-FFI test (Neuroticism,
Extraversion, Openness-Five Factor Inventory) 
and of the SCL-90-R (Symptom Check List)  were
used. Both tests are self-report questionnaires.
The NEO-FFI assesses 5 personality dimensions
(Table 1), which are considered the major dimensions of
the human personality.  This inventory is reliable when
retesting over time, and is therefore independent of current
life circumstances.  It consists of 60 items (12 for
each personality dimension). The item analysis yields a
score for each personality dimension.
The SCL-90-R is used to assess psychological distress
in patients, including patients with chronic pain. [18–20] The
SCL-90-R is a multidimensional checklist with 90 items,
each describing a physical or psychological symptom.
The item analysis yields scores for 9 dimensions (Table
1). In addition, a score for the general psychological
distress (general severity index) is calculated.
The normal range of the scores of both NEO-FFI and
SCL-90-L is 40 to 60. A score greater than 60 indicates
an abnormality of the corresponding psychological
Intensity of the neck pain
The subjects were asked to quantify the intensity of
the neck pain at rest on a 10–cm visual analog scale
(VAS), where 0 indicates no pain and 10 the worst pain
imaginable. Then the subjects were asked to move the
head to maximal flexion, extension, and rotation to the
right and to the left. The VAS during the movement
evoking the strongest pain was recorded.
Main variables: sensory assessments
The basic procedure was a gradual increase in the
stimulus intensity until the intensity at which the perception
turned to a painful sensation (pain detection threshold)
or the intensity at which the pain was perceived as
intolerable (pain tolerance threshold) was identified. All
the assessments were made before and after local anesthesia
of the painful and tender points (see Local Anesthesia
The following assessments were performed, in a randomized
order: pain detection threshold on intramuscular
electrical stimulation (single stimulus),  temporal summation
threshold on intramuscular  and transcutaneous 
repeated electrical stimulation, heat pain tolerance
The locations of the sensory tests is illustrated in Figure
1. Each test was performed at a cervical and a lumbosacral
dermatome of the same side, in a randomized
order. In the control group, the cervical dermatome (C3
or C4) and the side of cervical and lumbosacral stimulation
(right or left) were randomly selected. In patients,
the tests were applied at the most painful cervical dermatome,
at least 4 cm from the sites selected for local
anesthesia. For lumbosacral stimulation of both groups,
intramuscular electrical stimulation was applied in the
tibialis anterior muscle, 14 cm distal to the middle of the
patella, 2 cm lateral to the lateral edge of the tibia. 
Transcutaneous electrical stimulation was performed at
the foot, 1 cm distal to the lateral malleolus.  Heat
stimulation was applied 2 cm lateral to the intramuscular
For each measurement, 3 threshold determinations
were made. The first one was used to get the subject
familiar with the measurement. The mean of the last 2
determinations was used for the data analysis.
Pain detection on intramuscular electrical stimulation
Two needle electrodes (Dantec, Skovlunde, Denmark)
with 3–mm-long uninsulated tips were inserted 2.0 cm
from the skin surface into the muscle.  The interelectrode
distance was 0.5 cm. A train of 5 square-wave
impulses (perceived as a single stimulus, each impulse 1
ms, total duration 25 ms) was delivered from a computercontrolled
constant-current stimulator (University of
Aalborg, Denmark). Based on empirical data of our
group, the 5 impulses (perceived as a single stimulus)
cause a better activation of thin fibers than a single pulse.
The current intensity was increased in steps of 0.1 mA
(from 0.2 to 2.0 mA), in steps of 0.5 mA (from 2.0 to 5.0
mA), and in steps of 1.0 mA (from 5.0 mA). After each
stimulus, the subject was asked if she or he perceived the
stimulus as painful. The stimulus intensity evoking a
distinct pain sensation (pain detection threshold) was
Temporal summation on intramuscular electrical stimulation
Repeated stimuli of constant intensity may evoke an
increase in the intensity of perception during the repeated
stimulation, so that the last stimuli are perceived as painful.  This phenomenon is called temporal summation of
nociceptive stimulation. Recordings of spinal reflex in
humans indicate that temporal summation results from a
short-lasting hyperexcitability of the spinal cord induced
by the repeated stimulation. [13, 23] To elicit temporal summation,
the stimulus burst so described, delivered
through the same electrodes, was repeated 5 times with a
frequency of 2 Hz.  The current intensity was increased
as described (see “Pain detection on intramuscular electrical
stimulation”), until the summation threshold was
identified. Summation threshold was defined as the current
intensity evoking an increase in perception during
the 5 stimulations, so that the last 1–to–3 stimuli were
perceived as painful.
Temporal summation on transcutaneous electrical stimulation
Two bipolar surface Ag/AgCl-electrodes (Dantec,
Skovlunde, Denmark) were placed on the skin, 5 mm
apart. Repeated electrical stimulation was performed as
described for intramuscular stimulation to determine the
temporal summation threshold.
Pain tolerance on heat stimulation
The computer-driven Thermotest (Somedic AB,
Stockholm, Sweden) was used. A thermode with a surface
of 25 × 16 mm was applied to the skin. The temperature
of the thermode was continuously increased
from 30°C to a maximum of 52°C at a rate of 2.0°C/s.
The subject was asked to press a button when she or he
perceived the pain as intolerable. At that point, the temperature
was recorded by the software and the thermode
cooled to 30°C. The thermode also cooled to 30°C even
if the tolerance threshold was not reached at 52°C. In this
case, 52°C was considered as tolerance threshold. The
heat pain tolerance threshold (i.e., the stimulus intensity
evoking intolerable pain) was preferred to the detection
threshold (i.e., the intensity at which the stimulus perception
turns to a painful sensation) because the former
seems to produce a stronger activation of the C-fibers. 
Activation of the C-fibers is primarily involved in the
induction of central hypersensitivity. 
Subjects of the whiplash group were examined for the
presence of painful and tender points at the neck. Painful
points were defined as areas of spontaneous pain. Tender
points were defined as areas where pain could be evoked
by palpation or movement that would not normally be
painful. Each point was infiltrated with an intramuscular
injection of 1 ml lidocaine 1%. [25, 26] For the control
group, one lidocaine infiltration (1 ml) was performed at
the same cervical dermatome where the sensory tests
Time schedule of the experiment
First, the psychological tests were performed and the
intensity of neck pain was measured. The subjects then
tried all the sensory tests for training. When they were
familiar with them, basal measurements of all the sensory
tests were performed. The sensory tests and the
measurements of neck pain were repeated 15, 45, and 75
minutes after local anesthesia. At 45 and 75 minutes, the
single-stimulus intramuscular electrical stimulation was
omitted to avoid an excessively long testing procedure.
Because of the relatively small sample size and the
non-normal distribution of several data, nonparametric
tests were used.
The two groups were compared for age, weight,
height, body mass index (weight in kilograms divided by
the square of the height in meters) and psychological
variables using the Mann-Whitney rank sum test. The
effect of the local anesthesia on the intensity of neck pain
in the whiplash group was analyzed by the Friedman
repeated measures analysis of variance on ranks.
Main variables (study hypotheses)
The first hypothesis (see the introduction) was tested
by comparing the two groups for the pain thresholds
measured before the local anesthesia. The one-tailed
Mann-Whitney rank sum test with the Bonferroni correction
was used for each sensory test. The second hypothesis
was tested by analyzing the time course of each
pain threshold (i.e., before and after local anesthesia)
using the Friedman repeated measures analysis of variance
on ranks. The analyses were performed separately
for each group.
The statistical software used was the SPSS (Chicago,
IL, U.S.A.), version 9.0. A p value less than 0.05 was
considered as significant.
In the whiplash group, neck pain began within 24
hours after the accident in all patients. The median
(25th–75th percentiles) duration of pain was 40 (16–71)
months. The median (25th–75th percentiles) intensity
of neck pain before the infiltration at rest and during
movement was 3.2 (2.3–4.4) and 6.4 (4.9–7.1) cm,
In the whiplash and the control group, the median
(25th–75th percentiles) of age was 48 (35–54) and 41
(35–43) years, respectively, the weight 74 (55–85)
and 64 (58–71) kg, the height 166 (164–175) and 172
(169–177) cm, and the body mass index 25 (21–27) and
22 (20–23) kg/m2. The number of females/males was 8/6
and 7/7, respectively. For all these variables, the p value
Data pertaining to the psychological variables are presented
in Table 1. The patients exhibited no abnormal
personality traits. On the SCL-90-R, however, they exhibited
profiles of distress, with major elevations in somatization,
depression, and general severity index, and
lesser elevations in obsession–compulsion, anxiety, hostility,
and paranoid ideation.
The basal pain thresholds were significantly lower in
the whiplash group than in the control group for all tests,
except heat (Figures 2–5). This difference was observed at
both neck and lower limb. Concerning pain tolerance on
heat stimulation at the neck, 2 patients in the whiplash
group and 2 patients in the control group had thresholds
higher than the maximum allowed value of 52°C; at the
leg, this value was reached in 7 and 5 patients in the
whiplash and the control group, respectively.
In the whiplash group, 1–to–4 painful and tender points
(median 3) were identified and infiltrated with the local
anesthetic. In this group, there was no statistically significant
change in any pain threshold after local anesthesia
(Figs. 2–5). No significant changes in the intensity of
neck pain after the infiltration were observed (Figure 6).
The present study focused on the central mechanisms
involved in chronic pain after whiplash injury. We found
that the stimulus intensity that has to be applied to evoke
pain is lower in patients than in healthy subjects (Figs.
2–4). This indicates a state of hypersensitivity of the
nociceptive system to peripheral stimulation. The hypersensitivity
was observed with both cutaneous and muscular
stimulation, applied at both the neck (i.e., the injured
area) and the lower limb (i.e., a healthy area). This
indicates that an alteration in the processing of sensory
stimuli in the central nervous system is involved in the
generation of hypersensitivity. Because the local anesthesia
of the painful and tender points did not affect the
pain thresholds, the central hypersensitivity was not
maintained by a nociceptive input arising from these
In animal preparations, tissue damage causes an increased
responsiveness of spinal cord neurons to peripheral
stimulation3 that is also observed for the limb contralateral
to the site of injury.  After injury, responses of
dorsal horn  or thalamic  neurons are elicited by
stimuli applied at peripheral tissues that did not evoke
any response of the same neurons before the injury (expansion
of receptive fields). As a result, a peripheral
stimulus activates a higher number of dorsal horn neurons
and hyperalgesia may also be evoked in areas
outside the injured region. These observations suggest
the possibility that mechanisms such as central “sensitization”
underlie the reduced pain thresholds that we
found in patients with neck pain after whiplash injury.
Specifically, nociceptive stimulation associated with the
injury may produce excitation of the central nervous system,
which in turn is responsible for reduced pain thresholds
after stimulation of healthy tissues. In this sense the
central hypersensitivity that we found may be explained
as central “sensitization.”
The fact that hypersensitivity was observed at both
neck and leg to the same extent indicates a state of generalized
central nervous system hypersensitivity, which
is consistent with previous investigations. [5, 6] This finding
suggests that central hypersensitivity alone can not explain
the pain syndrome, because pain is not generalized,
but regional. Rather, the role of central hypersensitivity
is more likely an amplification of a nociceptive input
arising from a focus in the neck. The absence of objective
signs of tissue damage is common in patients with
neck pain after whiplash injury.  Conversely, lesions in
the zygapophysial joints associated with pain are frequently
not detected by medical imaging or physical
examination.  Central hypersensitivity could explain
exaggerated pain after minimal nociceptive input arising
from minimally damaged tissues in the neck.
Patients with fibromyalgia display generalized hyperalgesia
that is detectable also in nonpainful tissues. 
This finding is similar to the generalized hyperexcitability
that we found in whiplash patients. Patients with fibromyalgia
have increased levels of substance P  and
excitatory amino acids  in the cerebrospinal fluid,
which may be involved in the induction of generalized
hyperexcitability of the central nervous system. It is not
known whether these biochemical changes are present in
We found a significant difference between the groups
in the pain threshold with all the tests used, except heat
(Fig. 5). This is consistent with previous evidence that
tissue damage does not result in secondary hyperalgesia
to heat stimulation. [8, 9, 34, 35] A recent study conducted on
patients with chronic temporomandibular joint pain came
to the similar results. Patients, compared with healthy
controls, had more pain after intramuscular injection of
hypertonic saline and lower pain threshold to pressure
stimulation. However, no difference between the groups
in heat pain thresholds was found. 
Modulation of central hypersensitivity by local anesthesia
This is the first study in which the effect of nociceptive
input on central hypersensitivity in whiplash patients
has been investigated. After local anesthesia of the painful
and tender points, no significant changes in the intensity
of neck pain were observed (Fig. 6). Therefore,
the main source of the pain complaints was not located at
these points. None of the pain thresholds was affected by
local anesthesia (Figs. 2–5). Therefore, the hypersensitivity
was not maintained by nociception arising from the
painful and tender points.
It is possible that central hypersensitivity was maintained
by pathologic processes located in other structures
of the neck. In this case, the painful and tender points
may have been areas of referred pain (i.e., pain reported
in areas that are at distance from the diseased tissue).
Painful muscular stimulation in the rat induces the appearance
of new receptive fields in nociceptive dorsal
horn neurons, so that these neurons receive input from
deep tissues that are at distance from the site of painful
stimulation.  This suggests that central mechanisms
may lead to a mislocation of the source of pain. Local
anesthesia of the referred pain area reduces the intensity
of referred pain by 40% after experimentally induced
muscle pain.  Based on these data, it can be hypothesized
that in whiplash patients a nociceptive focus located
in deep tissues of the neck maintains the state of
central hypersensitivity, and the painful and tender points
are areas of referred pain. This would explain why local
anesthesia of these areas produced a minimal decrease in
the pain intensity (Fig. 6) and no change in the central
responsiveness to peripheral stimulation (Figs. 2–5). In a
subgroup of whiplash patients, pain arises from the zygapophysial
joints.  In these patients, local anesthetic
block of the nerves that supply the joints abolishes
pain.  Future research may investigate the effect of nociceptive
input on central hypersensitivity in patients
with zygapophysial joint pain by means of selective
Central hypersensitivity may not necessarily require
an ongoing nociceptive input. Injury produced by intradermal
injection of capsaicin9 induces hyperalgesia in
surrounding tissues that is prevented by anesthetizing the
skin before the injury. However, hyperalgesia is not prevented
when the skin is anesthetized after the injury. This
indicates that an initial peripheral event is required to
induce central hypersensitivity. Once established, central
hypersensitivity may be independent of the peripheral
input. Local anesthesia after induction of burn injury
reduces but not abolishes hyperalgesia.  This indicates
that peripheral nociceptive input contributes to, but may
not be the only determinant of, central hypersensitivity,
at least in experimentally-induced hypersensitivity. If
these observations apply to patients, it can be hypothesized
that central hypersensitivity in whiplash patients
may persist after resolution of the initial tissue damage.
However, as mentioned previously, a generalized central
hypersensitivity in the absence of a minimal nociceptive
input arising from the neck is unlikely to explain chronic
neck pain in whiplash patients.
This investigation provides evidence for neurobiologic
changes that are not associated with alterations in the
personality traits (Table 1). This information is new, because
the previously published studies on central hypersensitivity
in whiplash did not analyze psychological factors. [5, 6] Simulated low thresholds by patients are very
unlikely based on the following considerations: patients
were informed before the study and agreed that they
would not receive any advantage from the results; and
the threshold to heat stimulation was not different in the
two groups, which indicates that there was no attitude for
simulating low pain thresholds.
Consistent with previous research,20 we found psychological
distress in whiplash patients (Table 1). The psychological
profile of whiplash patients as assessed by the
SCL-90-R is similar to the profile of patients with
chronic pain resulting from other musculoskeletal injuries.  Psychological distress possibly contributed to the
increased pain sensitivity. However, if psychological
factors were the primary determinant of altered pain perception,
they would probably affect all the pain thresholds.
Again, no difference in the heat pain threshold between
patients and controls was found, which is
consistent with previous studies on experimental hyperalgesia
(see Central Hypersensitivity section). Heat pain
threshold is reduced by experimentally-induced anxiety
in humans.  This finding does not support the possibility
that psychological distress may have spared heat pain
selectively in our study.
Multiple pathways that connect forebrain sites involved
in analgesic mechanisms related to emotional
states with the dorsal horn have been identified. 
Descending facilitatory and inhibitory pathways may
affect the development of spinal cord hyperexcitability
after inflammation and tissue damage in the animal. 
It can be hypothesized that psychological distress
causes a “disregulation” in the descending modulation
of spinal cord excitability in whiplash patients, which
results in enhancement of the injury-induced central
Finally, it is also possible that chronic pain results both
in central hypersensitivity and psychological distress,
which are not causally related, but have a common cause.
Limitations of the study
There is no reliable sensory examination by which
adequate anesthesia of muscles can be ascertained. Failure
to provide pain relief after local anesthesia may have
been the result of either absence of a nociceptive focus in
the muscle (as previously mentioned) or failure to anesthetize
a nociceptive focus located in the muscle. In both
cases, examination of the painful and tender points after
the infiltration would not help finding the cause of failure,
since it would lead to the same result, that is, persistence
of tenderness. Although the infiltration was performed
by an experienced pain specialist, we cannot rule
out that in some patients a nociceptive focus, if present,
was not adequately anesthetized.
Lack of statistically significant difference in heat pain
thresholds between the groups is an important finding. In
some subjects, the heat pain tolerance threshold was
higher than the maximum allowed value of 52°C (see
Results), which should not be overcome to avoid burn
injuries. The number of subjects reaching 52°C was not
lower in the whiplash than in the control group, which
supports the finding that patients did not display hypersensitivity
to heat. As mentioned previously, absence of
hypersensitivity to heat is supported by several experimental
studies and a recent clinical investigation. However,
we cannot rule out that a statistically significant
difference in heat thresholds would be found if the test
allowed measurements above 52°C and/or a higher number
of subjects had been analyzed.
Chronic pain after whiplash injury is associated with
central hypersensitivity. In our patient population, central
hypersensitivity was not affected by local anesthesia
of the painful and tender areas. This alteration in the
central processing of nociceptive stimuli is not necessarily
associated with detectable tissue damage and modifications
in the personality traits.
Studies on experimentally-
induced central hypersensitivity support three
(1) maintenance of central hypersensitivity by an ongoing peripheral nociceptive input,
(2) persistence of central hypersensitivity after resolution of the primary peripheral event, and
(3) imbalance of the descending modulatory system.
The relative contribution of
these mechanisms is unknown. Central hypersensitivity
should be considered as a possible mechanism underlying
whiplash pain, even when no organic lesions are
identified by the common diagnostic methods. The development
of therapeutic procedures aiming at preventing
or treating central hypersensitivity is an important
field of future research.
The authors thank Prof. Anthony H.
Dickenson (Department of Pharmacology, University College,
London, UK) for reviewing the paper; and Dr. Pietro Ballinari,
statistician at the Department of Psychology of the University
of Bern (Switzerland), for performing the statistical analyses.
Spitzer WO, Skovron ML, Salmi LR.
Scientific Monograph of the Quebec Task Force on Whiplash-Associated Disorders
Redefining “Whiplash” and its Management
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 findings.
Evidence for a central component of post-injury pain hypersensitivity.
Nature (London) 1983;306:686–8.
Coderre TJ, Katz J.
Peripheral and central hyperexcitability: differential signs and symptoms in persistent pain.
Behav Brain Sci 1997;20:404–19.
Sheather Reid RB, Cohen ML.
Psychophysical evidence for a neuropathic component of chronic neck pain.
Koelbaek Johansen M, Graven-Nielsen T, Schou Olesen A, et al.
Generalized muscular hyperalgesia in chronic whiplash syndrome.
Torebjörk HE, Lundberg LE, LaMotte RH.
Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans.
J Physiol (London) 1992;448: 765–80.
Dahl JB, Brennum J, Arendt-Nielsen L, et al.
The effect of preversus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin.
Pain 1993;53: 43–51.
LaMotte RH, Shain CN, Simone DA, et al.
Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms.
J Neurophysiol 1991;66:190–211.
Gracely RH, Lynch SA, Bennett GJ.
Painful neuropathy: altered central processing maintained dynamically by peripheral input.
Curatolo M, Petersen-Felix S, Arendt-Nielsen L.
Sensory assessment of regional analgesia in humans. A review of methods and applications.
Induction and assessment of experimental pain from human skin, muscle and viscera.
In: Jensen TS, Turner JA, Wiesenfeld-Hallin Z, eds.
Proceedings of the 8th World Congress on Pain.
Seattle: IASP Press, 1997:393–425.
Arendt-Nielsen L, Brennum J, Sindrup S, et al.
Electrophysiological and psychophysical quantification of central temporal summation of the human nociceptive system.
Eur J Appl Physiol 1994; 68:266–73.
Curatolo M, Petersen-Felix S, Arendt-Nielsen L, et al.
Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.
Anesth Analg 1998;86:341–7.
Borkenau P, Ostendorf F.
NEO-Fünf-Faktoren Inventar (NEOFFI) nach Costa und McCrae.
Göttingen, Germany: Hogrefe, 1993.
Die Symptom-Checkliste von Derogatis. Deutsche Version.
Göttingen, Germany: Beltz, 1995.
Costa PT, Jr., McCrae RR, Zonderman AB, et al.
Cross-sectional studies of personality in a national sample: 2. Stability in neuroticism, extraversion, and openness.
Psychol Aging 1986;1:144–9.
Bernstein IH, Jaremko ME, Hinkley BS.
On the utility of the SCL-90-R with low-back pain patients.
Duckro PN, Margolis RB, Tait RC.
Psychological assessment in chronic pain.
J Clin Psychol 1985;41:499–504.
Wallis BJ, Lord SM, Bogduk N.
Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomized, double-blind, placebo-controlled trial.
Laursen RJ, Graven-Nielsen T, Jensen TS, et al.
Quantification of local and referred pain in humans induced by intramuscular electrical stimulation.
Eur J Pain 1997;1:105–13.
Arendt-Nielsen L, Nielsen J, Petersen-Felix S, et al.
Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain.
Br J Anaesth 1996;77:625–31.
Characteristics of second pain and flexion reflexes indicative of prolonged central summation.
Exp Neurol 1972;37: 371–87.
Brennum J, Arendt-Nielsen L, Horn A, et al.
Quantitative sensory examination during epidural anesthesia and analgesia in man: effects of morphine.
Hong CZ, Hsueh TC.
Difference in pain relief after trigger point injections in myofascial pain patients with and without fibromyalgia.
Arch Phys Med Rehabil 1996;77:1161–6.
Hameroff SR, Crago BR, Blitt CD, et al.
Comparison of bupivacaine, etidocaine, and saline for trigger-point therapy.
Anesth Analg 1981;60:752–5.
Long term alterations in the excitability of the flexion reflex produced by peripheral tissue injury in the chronic decerebrate rat.
McMahon SB, Wall PD.
Receptive fields of rat lamina 1 projection cells move to incorporate a nearby region of injury.
Pain 1984;19: 235–47.
Guilbaud G, Kayser V, Benoist JM, et al.
Modifications in the responsiveness of rat ventrobasal thalamic neurons at different stages of carrageenin-produced inflammation.
Brain Res 1986;385: 86–98.
Baillieres Best Pract Res Clin Rheumatol 1999;13:261–85.
Sörensen J, Graven Nielsen T, Henriksson KG, et al.
Hyperexcitability in fibromyalgia.
J Rheumatol 1998;25:152–5.
Russell IJ, Orr MD, Littman B, et al.
Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.
Arthritis Rheum 1994;37:1593–601.
Larson AA, Giovengo SL, Russell IJ, et al.
Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways.
Raja SN, Campbell JN, Meyer RA.
Evidence for different mechanisms of primary and secondary hyperalgesia following heat injury to the glabrous skin.
Campbell JN, Khan AA, Meyer RA, et al.
Responses to heat of C-fiber nociceptors in monkey are altered by injury in the receptive field but not by adjacent injury.
Svensson P, List T, Hector G.
Analysis of stimulus-evoked pain in patients with myofascial temporomandibular pain disorders.
Hoheisel U, Mense S, Simons DG, et al.
Appearance of new receptive fields in rat dorsal horn neurons following noxious stimulation of skeletal muscle: a model for referral of muscle pain?
Neurosci Lett 1993;153:9–12.
Laursen RJ, Graven-Nielsen T, Jensen TS, et al.
The effect of compression and regional anesthetic block on referred pain intensity in humans.
Lord SM, Barnsley L, Wallis BJ, et al.
Chronic cervical zygapophysial joint pain after whiplash. A placebo-controlled prevalence study.
Peebles JE, McWilliams LA, MacLennan a R.
A comparison of symptom checklist 90-revised profiles from patients with chronic pain from whiplash and patients with other musculoskeletal injuries.
Rhudy JL, Meagher MW.
Fear and anxiety: divergent effects on human pain thresholds.
Dubner R, Ren K.
Endogenous mechanisms of sensory modulation.
Return to the WHIPLASH Section
Return to the CHIROPRACTIC AND CHRONIC NECK PAIN Page