Clemens Forster

One hundred ninety-four cutaneous C-fibers were recorded from the human peroneal nerve; 118 units were found by mechanical stimuli and 76 units were detected by electrical stimulation through a surface electrode. Needle electrodes were then inserted for electrical intradermal stimulation in the innervation territory of the units. Afferent and efferent sympathetic C-fibers were identified by slowing of conduction velocity after activation either by physical or chemical skin stimuli, or by arousal maneuvers eliciting sympathetic reflexes. In addition to mechano-heat-responsive C units (CMH) also found in previous studies, we here report on novel classes of C nociceptors in human skin, namely, units responding only to mechanical stimuli (CM), units responding only to heating (CH), and units that were insensitive to mechanical and heating stimuli and also to sympathetic provocation tests (CMiHi). With the electrical search technique we found 45% CMH, 13% CM, 6% CH, 24% CMiHi, and 12% sympathetic units. Excitation by topically applied mustard oil occurred in 58% of CMH units, and in one-third of CM and CMiHi units, respectively. Some CM, CH, and CMiHi units were sensitized to heating and/or to mechanical stimuli after topical application of mustard oil or capsaicin. These units then acquired responsiveness to a stimulus modality to which they previously were insensitive. Such recruitment of previously silent nociceptors implies spatial summation to the nociceptive barrage at central levels, and may contribute both to primary hyperalgesia to heat and pressure after chemical irritation, and to secondary hyperalgesia as a consequence of central sensitization.

Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.

1. The aim of this investigation was to study the peripheral neural mechanisms of the C-fiber-mediated modalities of burning pain and itch by the use of microneurography of human unmyelinated afferents. 2. Sixteen stable recordings of single C-fibers and 6 multiunit recordings were obtained from the superficial radial nerves of volunteers. All units were excited by stimulating their receptive fields with von Frey bristles (range 10-600 mN), and all but four units were also driven by radiant heat stimulation. 3. Histamine was iontophoretically applied to the receptive fields of these units for 20 or 30 s and was found to provoke itching sensations lasting several minutes, together with wheal and flare responses. Subsequently a solution containing 20 or 30% mustard oil was applied to the receptive field of the respective unit, which provoked a sensation of burning pain. 4. One-half of the units were excited by histamine, and the median discharge rates derived from interspike intervals ranged from approximately 0.1 to 0.8 Hz. Mustard oil-induced activity was observed in all histamine-sensitive units and also in three single units and in one multiunit recording that revealed no histamine response. Median interval-derived discharge rates ranged from 0.2 to 1.2 Hz. 5. Analysis of the interspike interval distribution and of the autocorrelation function derived from the chemically induced discharges of single units provided no evidence for an encoding of itch and burning pain in different discharge patterns of units responding to histamine and to mustard oil.(ABSTRACT TRUNCATED AT 250 WORDS)