Neuropathic pain : somatosensory functions related to spontaneous ongoing pain, mechanical allodynia and pain relief

摘要

Introduction and aim: Patients with neuropathic pain suffer fromspontaneous ongoing pain and from abnormal stimulus-evoked pain, e.g.,allodynia. Dynamic mechanical allodynia (DMA) is evoked by a normallyinnocuous light moving mechanical stimulus on the skin and staticmechanical allodynia (SMA) by a sustained, normally innocuous pressureagainst the skin. Some patients report variable intensity of DMA which attimes is only unpleasant, i.e., dynamic mechanical dysesthesia (DMD). Theaim was to probe for common denominators of sensory disturbances linkedto mechanisms underlying development of or protection against pain aftera traumatic peripheral nerve injury (Study I). Also, we aimed atexamining if short or longer lasting non-painful von Frey filamentstimulation of the neuropathic skin could be used to assess perceptionthresholds to DMA and SMA (Study II). Further, we investigated if DMA isthe hyperbole of DMD both mediated by Abeta fibres in the periphery(Study III). Finally, we explored the modulatory effect of spinal cordstimulation (SCS) on somatosensory functions within the painful area(Study IV).Methods: Using methods of quantitative sensory testing a detailedanalysis of somatosensory functions was performed in patients with andwithout pain after a traumatic peripheral nerve injury (Study I) and inpatients reporting a sustained pain relieving effect of at least 30 %following SCS (Study IV). A compression/ischemia-induced (differential)nerve block in conjunction with repeated quantitative sensory testing ofA-delta and C-fibre function was used to assess which nerve fibrepopulation that contributes to pain at perception threshold level using 1s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin (StudyII). The same approach was used to study which part of the peripheralfibre spectrum that contributes to DMA and DMD (Study III).Results: Pain patients reported allodynia to cold and pressure inconjunction with an increase in the perception threshold to non-painfulwarmth on the injured side compared to the uninjured side. Painfreepatients reported hypoesthesia to light touch, cold and warmth on theinjured side. No significant difference could be demonstrated comparingside-to-side differences between patients with and without pain. Duringthe nerve block elevation of vF1 and vF10 occurred simultaneously andsignificantly prior to an increase in the perception level to cold orwarmth. During the nerve block there was a transition of DMA to DMD inall patients with peripheral neuropathic pain and in 3/7 patients withcentral post stroke pain. Remaining patients lost DMA without transition.The transition/loss of DMA occurred early and concurrently in time in allpatients paralleled by a continuous impairment of mainly A-beta fibrefunction. Following SCS decreased perception threshold to light touch andincreased perception threshold to pressure pain were found in theneuropathic area when comparing with pre-stimulation values. Compared tothe contralateral side these perception thresholds changed towardsnormalisation also including a significant normalisation of theperception threshold to non painful cold. SCS did not alter sensitivityto noxious temperature stimulation.Conclusions: Increased pain sensitivity to cold and pressure was found onthe injured side in pain patients, pointing to hyperexcitability in thepain system, not verified by a more challenging analysis of side-to sidedifferences between patients with and without pain. A-beta fibres are theperipheral mediators of both vF1 and vF10 although different receptororgans may be involved, i.e., rapidly (RA) and slowly (SA-I) adaptingmechanoreceptors, respectively. We suggest DMA to be the hyperbole ofDMD, the difference being the number of mechanoreceptive fibres havingaccess to the nociceptive system. Sensory alterations following SCSindicate a possible link to the release of a functional block onsomatosensory function induced by activity in the nociceptive system. Nosignificant correlation could be demonstrated between the degree ofthreshold alterations versus the degree of SCS-induced pain relief.