and concluded that relief from these symptoms with keta-
mine indicates a reduction in central sensitisation. However,
not all patients with nociceptive and/or neuropathic pain
respond to ketamine. In some studies, barely 30% had a
beneficial effect . Although several reports have suggested
that the likelihood of response is increased in younger
patients with a shorter history of pain , in fact this
response remains largely unpredictable. For example, the
best results in one study were obtained in two patients with a
prolonged (12–20 year) history of disease . For many
authors, this might suggest that only a subset of FM patients
has symptoms mediated by NMDA receptor mechanisms
. Moreover, since intolerable psychotomimetic side-
effects are frequently reported , it is important to identify
within a population of hyperalgesic FM patients those who
might respond to ketamine.
In the present study conducted in hyperalgesic FM
patients at rest, we showed that hypoperfusion of the medial
frontal and anterior cingulate cortex was highly predictive
of non-response to ketamine (PPV=100% and NPV=91%),
and independent of initial pain intensity. Decreased synaptic
activity in this area, assumed to be related to apathy, has also
been observed in chronic pain conditions. Gracely et al.
found that, compared with healthy patients, painful stimu-
lation in FM patients induced smaller activations in the
anterior cingulate cortex . The authors suggested that FM
patients develop a central processing of pain adapta tion that
reduces affective appraisal and responsiveness to pain. This
adaptative mechanism may in fact maintain pain, probably
induces treatment resistance and thus accounts for the
varying likelihood of response to ketamine. FM patients
with frontocingulate hypoperfusion would therefore proba-
bly benefit from cognitive therapy before ketamine, in order
to adjust their responsiveness to pain.
This prospective study showed that brain perfusion
SPECT may predict response to ketamine in hyperalgesic
FM patients. Larger studies and follow-up data, however,
will be necessary to determine the long-term predictive
value of these results.
1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence
and characteristics of fibromyalgia in the general population.
Arthritis Rheum 1995;38:19–28.
2. Guedj E, Taieb D, Cammilleri S, Lussato D, de Laforte C, Niboyet
J, et al.
Tc-ECD brain perfusion SPECT in hyperalgesic
fibromyalgia. Eur J Nucl Med Mol Imaging. 2007;34:130–4.
3. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic
resonance imaging evidence of augmented pain processing in
fibromyalgia. Arthritis Rheum 2002;46:1333–43.
4. Desmeules JA, Cedraschi C, Rapiti E, Baumgartner E, Finckh A,
Cohen P, et al. Neurophysiologic evidence for a central sensitization
in patients with fibromyalgia. Arthritis Rheum 2003;48:1420–9.
5. Hocking G, Cousins MJ. Ketamine in chronic pain management:
an evidence-based review. Anesth Analg 2003;97:1730–9.
6. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C,
Goldenberg DL, et al. The American College of Rheumatology
1990 criteria for the classification of fibromyalgia. Report of the
Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72.
7. Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson
M. Pain analysis in patients with fibromyalgia. Scand J Rheumatol
8. Graven-Nielsen T, Aspegren Kendall S, Henriksson KG, Bengtsson
M, Sorensen J, Johnson A, et al. Ketamine reduces muscle pain,
temporal summation, and referred pain in fibromyalgia patients. Pain
9. Mathisen LC, Skjelbred P, Skoglund LA, Oye I. Effect of
ketamine, an NMDA receptor inhibitor, in acute and chronic
orofacial pain. Pain 1995;61:215–20.
10. Haines DR, Gaines SP. N of 1 randomised controlled trials of oral
ketamine in patients with chronic pain. Pain 1999;83:283–7.
Eur J Nucl Med Mol Imaging