FW: Article 31-03 Fibromyalgia and chronic pain after injury

[Guest guest]

Apropros of our earlier discussion on chronic pain is this article by some

well known names in the centrally mediated pain research community. The

review was provided by Dan and forwarded to me by Harold McCoy.

D Freeman

Mailing address: 1165 Union Street NE, Suite 300

Salem, Oregon 97301

ph 503 586-0127

fax 503 763-3581

cell 503 871-0715

drmfreeman@...

Evidence for spinal cord hypersensitivity in chronic pain after whiplash

injury and in fibromyalgia

Pain, January 2004, Pages 7-15

Borut Banic, Steen sen-Felix, Ole K. Andersen, Bogdan P. Radanov, P. M.

Villiger, Lars Arendt-Nielsen and Michele Curatolo

FROM ABSTRACT:

Patients with chronic pain after whiplash injury and fibromyalgia patients

display exaggerated pain after sensory stimulation.

Because evident tissue damage is usually lacking, this exaggerated pain

perception could be explained by hyperexcitability of the central nervous

system.

The nociceptive withdrawal reflex (a spinal reflex) may be used to study the

excitability state of spinal cord neurons.

We tested the hypothesis that patients with chronic whiplash pain and

fibromyalgia display facilitated withdrawal reflex and therefore spinal cord

hypersensitivity.

Three groups were studied: whiplash (n=27), fibromyalgia (n=22) and healthy

controls (n=29).

Two types of transcutaneous electrical stimulation of the sural nerve were

applied: single stimulus and five repeated stimuli at 2 Hz. Electromyography

was recorded from the biceps femoris muscle. The main outcome measurement

was the minimum current intensity eliciting a spinal reflex (reflex

threshold).

Reflex thresholds were significantly lower in the whiplash compared with the

control group, after both single and repeated stimulation.

The same was observed for the fibromyalgia group, after both stimulation

modalities.

We provide evidence for spinal cord hyperexcitability in patients with

chronic pain after whiplash injury and in fibromyalgia patients.

This can cause exaggerated pain following low intensity nociceptive or

innocuous peripheral stimulation.

Spinal hypersensitivity may explain, at least in part, pain in the absence

of detectable tissue damage.

THESE AUTHORS ALSO NOTE:

³Peripheral injury and/or inflammation, induced experimentally in animals,

cause plasticity changes in the central nervous system that result in

neuronal hyperexcitability.²

[C.J. Woolf and M.W. Salter, Neuronal plasticity: increasing the gain in

pain. Science 288 (2000), pp. 1765x2013;1769].

³This central hypersensitivity causes exaggerated perception of painful

stimuli (hyperalgesia) and a perception of innocuous stimuli as painful

(allodynia).²

Patients with chronic pain after whiplash injury and with fibromyalgia have

exaggerated pain responses following sensory stimulation of healthy tissues.

Central hypersensitivity causes the nociceptive signal to be amplified, even

in the presence of minimal and undetectable soft tissue damage. [iMPORTANT]

These chronic pain patients could have irreversible plasticity changes in

the central nervous system.

The nociceptive withdrawal reflex is a spinal reflex of the lower extremity

that can be elicited by a painful stimulation of a sensory nerve. The

minimal intensity of the stimulus that is sufficient to elicit a reflex can

be electrophysiologically documented.

This method can be used to quantifying the excitability of spinal neurons.

All whiplash and fibromyalgia patients in this study had pain for more than

6 months.

In these patients, psychological assessment was performed by the self-report

questionnaires:

1) The German versions of the NEO-FFI test (Neuroticism, Extraversion,

Openness; Five Factor Inventory.

The NEO-FFI test assesses five personality dimensions (neuroticism,

extraversion, openness, agreeableness and conscientiousness), 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,

which is transformed into t-value adjusted to gender.

2) The SCL-90-R (Symptom Check List-90, revised version.

The SCL-90-R is used to assess psychological distress in patients, including

patients with chronic pain. The SCL-90-R is a checklist with 90 items, each

describing a physical or psychological symptom. The item analysis yields

scores for nine dimensions: somatization, obsession-compulsion,

inter-personal sensitivity, depression, anxiety, hostility, phobic anxiety,

paranoid ideation and psychoticism. In addition, a score for the general

psychological distress (general severity index) is calculated.

³The normal range of the scores of both NEO-FFI and SCL-90-R corresponds to

t-values between 40 and 60. t-Values greater than 60 indicates a pathology

of the corresponding psychological dimension.²

Pain intensity was quantified with a 10 cm visual analogue scale (VAS),

where 0 indicates no pain and 10 corresponds to the worst pain imaginable.

Muscle tenderness was measured with an electronic pressure algometer.

Pain detection threshold was defined as the point at which the pressure

sensation turned to pain.

Pain tolerance threshold was defined as the point at which the subject felt

pain as intolerable.

RESULTS

Regarding personality traits, all three groups scored within the normal

range (i.e. between 40 and 60),

³In contrast, both patient groups displayed considerably elevated scores on

several dimensions of the SCL-90-R, indicating psychological distress.

Particularly high scores were found in the fibromyalgia group.²

In the whiplash group, the median duration of pain was 22 months and the

median pain intensity was 3.7.

In the fibromyalgia group, the median duration of pain was 138 months, and

the median pain intensity was 4.6.

³Pressure pain detection and pressure pain tolerance thresholds were

significantly lower in both patient groups compared with the control

groups.²

15 whiplash patients and 16 fibromyalgia patients were not working because

of their condition.

³Reflex thresholds after single and repeated electrical stimulation were

significantly lower in both whiplash and fibromyalgia groups than in control

groups.² [iMPORTANT]

Median pain thresholds to electrical stimulation were lower in both patient

groups compared to control groups.

DISCUSSION

³The stimulus intensity necessary to evoke a spinal reflex is significantly

lower in patients with chronic pain after whiplash injury and in

fibromyalgia patients than in healthy subjects.²

³This demonstrates a state of hypersensitivity of spinal neurons to

peripheral stimulation.²

Seven cited previous studies on whiplash and fibromyalgia patients analyzed

the stimulus intensity necessary to evoke a pain sensation, and in each, the

pain threshold was lower in patients than in healthy subjects, which was

attributed to a possible hypersensitivity of the central nervous system.

³Thus the present study is the first one clearly demonstrating [objectively]

that spinal cord neurons are sensitized in chronic pain after whiplash

injury and in fibromyalgia.²

These authors also found lower median pain thresholds in whiplash and

fibromyalgia patients as compared to healthy subjects.

These authors found that reflex measurements may be more sensitive than pain

threshold measurements for detecting central hypersensitivity.

³The presence of spinal cord hypersensitivity in these two very different

pain syndromes suggests that this phenomenon may be present also in other

chronic musculoskeletal pain states.² [iMPORTANT,

synaptogenesis/neuroplasticity]

³Tissue damage and inflammation produce a variety of local biochemical

events that sensitize the peripheral receptors and may activate normally

inactive nociceptors.²

[Prostaglandin E2 from the omega-6 arachidonic cascade]

³Peripheral inflammation induces a gene expression in the dorsal root

ganglion resulting in an increased synthesis of peripheral receptors.²

[Receptive Field Enlargement]

This causes a reduced threshold for pain within the injured area.

³Peripheral tissue damage is not detected in many patients with chronic pain

after whiplash injury, although the available diagnostic tools may fail to

identify the peripheral source of pain.² [iMPORTANT]

In this study, because the electrical stimulation bypasses peripheral

receptors and activates directly the nerve fibers, the low reflex and pain

thresholds observed was not the result of peripheral sensitization, but from

altered spinal cord hypersensitivity.

³Tissue damage induces profound plasticity changes in the spinal cord that

result in increased responsiveness to peripheral stimulation.²

Why is this hypersensitivity is observed at tissues that are not injured and

distant from the site of pain?

An is explanation is ³expansion of receptive fields.² [iMPORTANT]

³As a result, a peripheral stimulus activates a higher number of dorsal horn

neurons and hyperalgesia may also be evoked in healthy areas surrounding the

injured region.² [iMPORTANT]

³Inflammation produces expression of cyclooxygenase-2 (COX-2) in the spinal

cord, which leads to prostaglandin production and neuronal

hyperexcitability.²

[Recall, COX-2 is an enzyme that converts the omega-6 fatty acid arachidonic

acid into the pro-inflammatory eicosanoid prostaglandin E2. The

pro-inflammatory eicosanoid prostaglandin E2 alters the thresholds of the

nociceptive afferent system, sending more pain afferentation into the spinal

cord.]

³Importantly, COX-2 expression is not confined to the neural structures

connected to the site of inflammation, but is observed in the whole spinal

cord and in supraspinal centers.²

³This may explain widespread spinal cord hyperexcitability after

inflammation and tissue damage.² [iMPORTANT]

Why is hypersensitivity observed in the absence of evident tissue damage?

Research has shown the occurrence of irreversible changes in the central

nervous system after tissue damage, such as ³expression of gene products,

destruction of inhibitory interneurons and aberrant excitatory connections.²

³These changes might persist after injury has healed, thereby explaining

persistent pain.² [iMPORTANT]

³Absence of evident tissue damage does not necessarily mean that there is no

tissue damage.² [VERY IMPORTANT]

³For instance, the zygapophysial joints have been identified as a frequent

source of pain after a whiplash injury, even when clinical and radiological

investigations do not show specific lesions of these joints.²

³Tissue damage, recognized or not by the available diagnostic methods,

induces persistent hyperexcitability of spinal cord neurons of patients that

is involved in persistent pain complaints.² [iMPORTANT]

³The underlying mechanism may be either a sustained central facilitation by

nociceptive input from an unrecognized peripheral focus or spinal cord

plasticity changes that persist after resolution of tissue damage.²

[iMPORTANT]

Elevated levels of substance P and excitatory amino acids [like glutamate]

have been found in the cerebrospinal fluid of fibromyalgia patients, and

they cause generalized spinal cord hyperexcitability. This may also occur in

the cerebrospinal fluid in whiplash patients.

Supraspinal mechanisms may also explain spinal cord hyperexcitability and

persistent pain.

³Spinal cord hyperexcitability elicited by trauma or inflammation is

influenced by descending facilitatory and inhibitory pathways.²

Some patients have a genetically reduction in serotonin production.

These patients have higher levels of depression, psychological distress and

pain

Serotonin is known to modulate descending pain control and

depression/psychological distress.

Consequently, ³the psychological distress typical of chronic pain conditions

is a determinant of spinal cord hyperexcitability via imbalance of

descending modulatory mechanisms² [from a reduction of serotonin

production].

CONCLUSIONS

³Using an objective assessment procedure, we found spinal cord

hyperexcitability in chronic pain after whiplash injury and in

fibromyalgia.²

³This finding can explain exaggerated pain following low intensity

nociceptive stimulation arising from areas of minimal and undetectable

tissue damage or pain after innocuous sensory stimulation.²

³Plasticity changes in the spinal cord excitability induced by peripheral

mechanisms, genetically driven biochemical alterations in the

neurotransmitter system and imbalance of descending modulatory pathways due

to psychological factors may be responsible for the neuronal

hypersensitivity.²

This ³study demonstrates that both patient groups have neurobiological

changes that are likely to alter the spinal nociceptive processing of

peripheral stimuli.

KEY POINTS FROM DAN MURPHY

1) Whiplash causes tissue damage.

2) This tissue damage is not recognized by available diagnostic

procedures.

3) Whiplash tissue damage produces inflammation, [primarily from the

conversion of the omega-6 fatty acid arachidonic acid into prostaglandin

E2].

4) This inflammation alters the thresholds of the nociceptive afferent

system, increasing pain.

5) This inflammation also induces a gene expression in the dorsal root

ganglion resulting in an increased peripheral receptors field. [Receptive

Field Enlargement]

This also increases pain.

6) This inflammation also increases the expression (production) of

cyclooxygenase-2 (COX-2) in the spinal cord, which is an enzyme that

converts the omega-6 fatty acid arachidonic acid into the pro-inflammatory

eicosanoid prostaglandin E2. The pro-inflammatory eicosanoid prostaglandin

E2 further alters the thresholds of the nociceptive afferent system, sending

more pain afferentation into the spinal cord.

7) This increased COX-2 expression is not confined to the neural

structures connected to the site of inflammation, but is observed in the

whole spinal cord and in supraspinal centers. This alters the pain

sensitivity of the entire body, including non-injured regions.

8) All of this induces profound plasticity changes

[synaptogenesis/neuroplasticity] in the spinal cord that result in increased

pain that can persist after all possible tissue healing has occurred.

9) Some of these spinal plastic changes may be irreversible (permanent

chronic pain syndromes).

10) This article objectively proves that patients with chronic pain have

hypersensitivity of the spinal cord neurons.

11) This article suggests that important diagnostic efforts for the

whiplash-injured patient include:

A)) The nociceptive withdrawal reflex (flexor reflex afferents is what

this is called in neurology diplomate class).

) The NEO-FFI test (Neuroticism, Extraversion, Openness; Five Factor

Inventory.

C)) The SCL-90-R (Symptom Check List-90, revised version.

D)) The visual analogue scale (VAS)

E)) The pressure algometer.

12) The absence of evident tissue damage does not necessarily mean that

there is no tissue damage.

13) Elevated levels of excitatory amino acids, like glutamate, are

often found in the cerebrospinal fluid of chronic pain patients, and cause

generalized spinal cord hyperexcitability. [Recall that glutamate is often

added to foods to enhance taste, and it does cross the blood-brain barrier

to enter the cerebral spinal fluid.]

14) Serotonin inhibits pain and inhibits depression. Reduced

serotonin may explain while chronic pain patients often suffer from

psychological distress.

COMMENT BY DAN MURPHY

I am currently involved in a whiplash case where the IME chiropractor

states:

³The patient has been substantially over-treated and any treatment extending

past the average 6-week expectation of recovery should not be reimbursed.

The appropriate number of treatments would more approximately be 14 to 16 in

the range of total cost of approximately $1,400.00.²

I believe this is wrong, and we will use this article as part of our

rebuttal to her report.