title: Differential endogenous pain modulation in complex-regional pain syndrome.
abstract: Endogenous pain modulation may provide facilitation or inhibition of nociceptive input by three main mechanisms. Firstly, modification of synaptic strength in the spinal dorsal horn may increase or decrease transmission of nociceptive signals to the brain. Secondly, local dorsal horn interneurons provide both feed-forward and feed-back modulation to spinothalamic and spinobulbar projection neurons. Thirdly, descending systems originating in the brainstem exert top-down modulation of nociceptive input at the spinal level. Not much is known on the activity of these systems in complex regional pain syndrome (CRPS). CRPS is a chronic pain condition characterized by burning pain and abnormalities in the sensory, motor and autonomous nervous system. In the present study, we tested changes in endogenous pain modulation in 27 CRPS patients compared with age-matched healthy controls. We applied repetitive noxious electrical stimuli (stimulation frequency 1 Hz) at the dorsal aspect of affected and unaffected hands in patients and to corresponding hands in controls. As known from previous studies this protocol simultaneously activates inhibitory and facilitatory pain modulating systems. This results in adaptation to the repetitive noxious stimulus, and simultaneously and at the same site, in development of an area of pinprick hyperalgesia. We measured (i) pain adaptation during the course of stimulation and (ii) the provoked area of pinprick hyperalgesia. These parameters were used as activity measures of pain inhibitory and pain facilitatory systems. As both measures result from gross inhibitory and gross facilitatory activity in pain modulatory systems, pain adaptation reflects net pain inhibition and area of pinprick hyperalgesia net pain facilitation. We found (i) decreased adaptation to painful electrical stimuli on both affected and unaffected hands of CRPS patients compared to healthy controls and (ii) increased areas of hyperalgesia on affected hands of CRPS patients compared to unaffected hands of CRPS patients and healthy controls. These findings imply a shift from inhibition towards facilitation of nociceptive input in CRPS patients, based on differential activation of subcomponents of the endogenous pain modulatory system. The differences were not correlated with duration of the disease, pain intensity, autonomic or motor function scores, presence or degree of evoked pain. However, significant correlation was found with the extent of adaptation and hyperalgesia on the unaffected hand. Thus, we hypothesize that differential activity in endogenous pain modulating systems may be not only a result of CRPS, but a potential risk factor for its development.
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Seifert
authors.forename: Georg
authors.initials: G
authors.lastname: Kiefer
authors.forename: Roberto
authors.initials: R
authors.lastname: DeCol
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Christian
authors.initials: C
authors.lastname: Maihöfner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000503:physiopathology; D020918:Complex Regional Pain Syndromes / Q000503:physiopathology / Q000523:psychology*; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006185:Habituation, Psychophysiologic; D006225:Hand / Q000473:pathology; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold; D011601:Psychophysics; D012684:Sensory Thresholds; D014110:Touch