Mechanical but not painful electrical stimuli trigger TNF alpha release in human skin.

Pro-inflammatory cytokines-in particular tumor necrosis factor (TNF)-alpha-play an important role in pain and hyperalgesia. The stimuli inducing TNF-alpha release in humans and the time course of this release are largely unknown. We performed dermal microdialysis in healthy subjects (n=36) during three experimental conditions: The first condition (control) was microdialysis without stimulation, the second condition was 30 min of electrical current stimulation (1 Hz, 20 mA, moderately painful), the third condition was 30 min of repetitive mechanical stimulation via an impact stimulator (bullet 0.5 g; velocity 11 m/s, minimally painful). TNF-alpha was quantified in the samples collected at the end of the baseline perfusion (about 1 h of saline perfusion), at the end of stimulation period (exactly 30 min after stimulation commenced) and at the end of the experiment (exactly 90 min after stimulation commenced) using a commercial enzyme-linked immunosorbent assay. The C-fiber-related flare was quantified with a laser-Doppler imager. ANOVA revealed that TNF-alpha levels increased during the eluate sampling period. At 90 min TNF-alpha in the eluate of the mechanical stimulation condition was significantly increased as compared to electrical current or control condition. Flare intensity was highest in the electrical current stimulation condition and only marginally different from control in mechanical stimulation. Our results show that minimal mechanical trauma is sufficient to induce significant TNF-alpha release in the skin. These results may be relevant to the treatment of posttraumatic pain disorders.

Warm and cold complex regional pain syndromes: differences beyond skin temperature?

OBJECTIVE: To investigate clinical differences in warm and cold complex regional pain syndrome (CRPS) phenotypes. BACKGROUND: CRPS represents inhomogeneous chronic pain conditions; approximately 70% patients with CRPS have "warm" affected limbs and 30% have "cold" affected limbs. METHODS: We examined 50 patients with "cold" and "warm" CRPS (n = 25 in each group). Both groups were matched regarding age, sex, affected limb, duration of CRPS, and CRPS I and II to assure comparability. Detailed medical history and neurologic status were assessed. Moreover, quantitative sensory testing (QST) was performed on the affected ipsilateral and clinically unaffected contralateral limbs. RESULTS: Compared with patients who had warm CRPS, patients who had cold CRPS more often reported a history of serious life events (p < 0.05) and chronic pain disorders (p < 0.05). In cold CRPS, the incidence of CRPS-related dystonia was increased (p < 0.05), and cold-induced pain had a higher prevalence (p < 0.01). Furthermore, QST revealed a predominant sensory loss in patients with cold CRPS (p < 0.05). In contrast, patients with warm CRPS were characterized by mechanical hyperalgesia (p < 0.05) in the QST of affected limbs. CONCLUSION: Our results indicate that warm and cold complex regional pain syndromes (CRPS) are associated with different clinical findings, beyond skin temperature changes. This might have implications for the understanding of CRPS pathophysiology.