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Scand J Pain. 2017 Dec 29;3(3):116-123. doi: 10.1016/j.sjpain.2012.01.002.

Differential pain modulation in patients with peripheral neuropathic pain
and fibromyalgia.
Gormsen L1, Bach FW 2, Rosenberg R3, Jensen TS1.

Abstract
Background The definition of neuropathic pain has recently been changed by the International
Association for the Study of Pain. This means that conditions such as fibromyalgia cannot, as sometimes
discussed, be included in the neuropathic pain conditions. However, fibromyalgiaand peripheral
neuropathic pain share common clinical features such as spontaneous pain and hypersensitivity toexternal stimuli. Therefore, it is of interest to directly compare the conditions. Material and methods In
this study we directly compared the pain modulation in neuropathic pain versus fibromyalgia by recording
responses to a cold pressor test in 30 patients with peripheral neuropathic pain, 28 patientswith fibromyalgia, and 26 pain-free age-and gender-matched healthy controls. Patients were asked torate their spontaneous pain on a visual analog scale (VAS (0-100 mm) immediately before andimmediately after the cold pressor test. Furthermore the duration (s) of extremity immersion in cold water
was used as a measure of the pain tolerance threshold, and the perceived pain intensity at pain
tolerance on the VAS was recorded on the extremity in the water after the cold pressor test. In addition,
thermal (thermo tester) and mechanical stimuli (pressure algometer) were used to determine sensory
detection, pain detection, and pain tolerance thresholds in different body parts. All sensory tests weredone by the same examiner, in the same room, and with each subject in a supine position. The
sequence of examinations was the following: (1) reaction time, (2) pressure thresholds, (3) thermal
thresholds, and (4) cold pressor test. Reaction time was measured to ensure that psychomotoric
inhibitions did not influence pain thresholds. Results Pain modulation induced by a cold pressor test
reduced spontaneous pain by 40% on average in neuropathic pain patients, but increased spontaneous
pain by 2.6% in fibromyalgia patients. This difference between fibromyalgia and neuropathic pain
patients was significant (P < 0.002). Fibromyalgia patients withdrew their extremity from the cold watersignificantly earlier than neuropathic pain patients and healthy controls; however, they had a higher
perceived pain intensity on the VAS than neuropathic pain patients and control subjects. Furthermore,neuropathic pain patients had a localized hypersensitivity to mechanical and thermal stimuli in theaffected area of the body. In contrast, fibromyalgia patients displayed a general hypersensitivity tomechanical and thermal stimuli when the stimuli were rated by the VAS, and hypersensitivity to some ofthe sensory stimuli. Conclusions These findings are the first to suggest that a conditioning stimulus
evoked by a cold pressor test reduced spontaneous ongoing pain in patients with peripheral neuropathicpain, but not in fibromyalgia patients when directly compared.

2The current study supports the notion that fibromyalgia and neuropathic pain are distinct pain conditions
with separate sensory patterns and dysfunctions in pain-modulating networks. Fibromyalgia should
therefore not, as sometimes discussed, be included in NP conditions. Implications On the basis of thefindings, it is of interest to speculate on the underlying mechanisms. The results are consistent with theidea that peripheral neuropathic pain is primarily driven from damaged nerve endings in the periphery,
while chronic fibromyalgia pain may be a central disorder with increased activity in pain-facilitating
systems.
KEYWORDS:
Cold pressor test; Fibromyalgia; Neuropathic pain; Pain thresholds
PMID:29913862
DOI:10.1016/j.sjpain.2012.01.002