This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.

Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E(2) (PGE(2)) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi(His-)), and 24 mechanoinsensitive, histamine-positive (CMi(His+)) units were compared. CMi(His+) units were most responsive to histamine and to PGE(2) and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi(His-) units showed significantly weaker responses to histamine, PGE(2), and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi(His+) units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi(His+) units but decreases with activation of CMH and CMi(His-) units.

Recent findings suggest that itch produced by intradermal insertion of cowhage spicules in human is histamine independent. Neuronal mechanisms underlying nonhistaminergic itch are poorly understood. To investigate which nerve fibers mediate cowhage induced itch in man, action potentials were recorded from cutaneous C-fibers of the peroneal nerve in healthy volunteers using microneurography. Mechano-responsive and -insensitive C-nociceptors were tested for their responsiveness to cowhage spicules, histamine, and capsaicin. Cowhage spicules induced itching and activated all tested mechano-responsive C-units (24/24, but no mechano-insensitive C-fibers (0/17). Histamine also induced itch, but in contrast to cowhage, it caused lasting activation only in mechano-insensitive units (8/12). In mechano-responsive C-units, histamine caused no or only short and weak responses unrelated to the time course of itching. Capsaicin injections activated four of six mechano-responsive fibers and three of four mechano-insensitive C-fibers. Cowhage and histamine activate distinctly different nonoverlapping populations of C-fibers while inducing similar sensations of itch. We hypothesize that cowhage activates a pathway for itch that originates peripherally from superficial mechano-responsive (polymodal) C-fibers and perhaps other afferent units. It is distinct from the pathway for histamine-mediated pruritus and does not involve the histamine-sensitive mechano-insensitive fibers.

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.

Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.

The aim of this study was to evaluate the psychophysical effects of both TRPA1 and TRPM8 activation in humans by application of either cinnamaldehyde or menthol. We applied 10% cinnamaldehyde or 40% menthol solutions on the forearm in 10 study participants. Quantitative sensory testing and laser Doppler imaging was performed before and after exposure to the compounds. Cinnamaldehyde evoked significant spontaneous pain and induced heat and mechanical hyperalgesia, cold hypoalgesia and a neurogenic axon reflex erythema. In contrast, TRPM8 activation by menthol produced no axon reflex reaction and resulted in cold hyperalgesia. We conclude that agonists of TRPA1 and TRPM8 channels produce strikingly different psychophysical patterns.

The complex regional pain syndrome (CRPS) is a disabling neuropathic pain condition that may develop following injuries of the extremities. In the present study we sought to characterize motor dysfunction in CRPS patients using kinematic analysis and functional imaging investigations on the cerebral representation of finger movements. Firstly, 10 patients and 12 healthy control subjects were investigated in a kinematic analysis assessing possible changes of movement patterns during target reaching and grasping. Compared to controls, CRPS patients particularly showed a significant prolongation of the target phase in this paradigm. The pattern of motor impairment was consistent with a disturbed integration of visual and proprioceptive inputs in the posterior parietal cortex. Secondly, we used functional MRI (fMRI) and investigated cortical activations during tapping movements of the CRPS-affected hand in 12 patients compared to healthy controls (n = 12). During finger tapping of the affected extremity, CRPS patients showed a significant reorganization of central motor circuits, with an increased activation of primary motor and supplementary motor cortices (SMA). Furthermore, the ipsilateral motor cortex showed a markedly increased activation. When the individual amount of motor impairment was introduced as regressor in the fMRI analysis, we were able to demonstrate that activations of the posterior parietal cortices (i.e. areas within the intraparietal sulcus), SMA and primary motor cortex were correlated with the extent of motor dysfunction. In summary, the results of this study suggest that substantial adaptive changes within the central nervous system may contribute to motor symptoms in CRPS.

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