Effect of Gelatin-Based Hemostats on Fibroblasts and Relevant Growth Factors in Wound Healing.

Gelatin-based hemostats have been used in various surgical fields and showed advantageous effects on central aspects of wound healing when compared to cellulose-based hemostats. Nevertheless, the influence of gelatin-based hemostats on wound healing has not been fully explored yet. Hemostats were applied to fibroblast cell cultures for 5, 30, 60 min, 24 h, 7 and 14 days and measurements were taken at 3, 6, 12, 24 h and 7 or 14 days, respectively. Cell proliferation was quantified after different exposure times and a contraction assay was conducted to measure the extent of the extracellular matrix over time. We further assessed quantitative levels of vascular endothelial growth factor and basic fibroblast growth factor using enzyme-linked immunosorbent assay. Fibroblast counts decreased significantly at 7 and 14 days independent of the application duration (p < 0.001 for 5 min application). The gelatin-based hemostat did not have a negative impact on cell matrix contraction. After application of gelatin-based hemostat, the basic fibroblast growth factor did not change; yet, the vascular endothelial growth factor significantly increased after a prolonged 24 h application time when compared to controls or to a 6 h exposure (p < 0.05). Gelatin-based hemostats did not impair contraction of the extracellular matrix or growth factor production (vascular endothelial growth factor and basic fibroblast growth factor), while cell proliferation diminished at late time points. In conclusion, the gelatin-based material seems to be compatible with central aspects of wound healing. For further clinical assessment, future animal and human studies are necessary.

Modality-specific facilitation of noninjurious sharp mechanical pain by topical capsaicin.

We had previously shown that a "blunt blade" stimulator can mimic the noninjurious strain phase of incisional pain, but not its sustained duration. Here, we tested whether acute sensitization of the skin with topical capsaicin can add the sustained phase to this noninvasive surrogate model of intraoperative pain. Altogether, 110 healthy volunteers (55 male and 55 female; 26 ± 5 years) participated in several experiments using the "blunt blade" (0.25 × 4 mm) on normal skin (n = 36) and on skin pretreated by a high-concentration capsaicin patch (8%, Qutenza; n = 36). These data were compared with an experimental incision (n = 40) using quantitative and qualitative pain ratings by numerical rating scale and SES Pain Perception Scale descriptors. Capsaicin sensitization increased blade-induced pain magnitude and duration significantly (both P < 0.05), but it failed to fully match the sustained duration of incisional pain. In normal skin, the SES pattern of pain qualities elicited by the blade matched incision in pain magnitude and pattern of pain descriptors. In capsaicin-treated skin, the blade acquired a significant facilitation only of the perceived heat pain component (P < 0.001), but not of mechanical pain components. Thus, capsaicin morphed the descriptor pattern of the blade to become more capsaicin-like, which is probably explained best by peripheral sensitization of the TRPV1 receptor. Quantitative sensory testing in capsaicin-sensitized skin revealed hyperalgesia to heat and pressure stimuli, and loss of cold and cold pain sensitivity. These findings support our hypothesis that the blade models the early tissue-strain-related mechanical pain phase of surgical incisions.

Differential perception of sharp pain in patients with borderline personality disorder.

BACKGROUND: Cutting is the most common method of non-suicidal self-injury (NSSI) to reduce inner tension in patients with Borderline Personality Disorder (BPD). Aim of this study was to compare pain perception induced by an incision and by application of a surrogate model for sharp mechanical pain (a non-invasive "blade") in BPD. METHODS: 22 female patients and 20 healthy controls (HC) received a small incision into the volar forearm, a 7s-blade application on the same side, and non-invasive phasic stimuli (pinprick, blade, laser, tactile). Pain intensity as well as affective versus sensory components were assessed. RESULTS: Incision was rated similarly by both groups (BPD: 28.6 ± 5.5 vs. HC: 33.9 ± 6.6; mean maximum pain ± SEM; p > 0.8), without significant difference for "7-s-blade" (BPD: 18.1 ± 3.8 vs. HC: 25.3 ± 3.6; mean maximum pain ± SEM; p > 0.17) or between "7-s-blade" and incision (BPD: p > 0.12; HC: p > 0.84). However, patients' intensity ratings returned significantly faster to baseline after incision (BPD: 38.9 ± 12.6 s vs. HC: 74.52 ± 11.5 s; p < 0.05), and patients evaluated "blade" and incision without any affective and with different sensory descriptors, indicating an altered evaluation of NSSI-like stimulation with qualitative in addition to quantitative differences-especially for the sharp pain component. CONCLUSIONS: The reduced perception of suprathreshold nociceptive stimuli is based on a missing affective component and specific loss of the perception of "sharpness" as part of the sensory component of pain. The results further demonstrate the usefulness of the "blade" for the perception of sharpness in patients. SIGNIFICANCE: Patients with Borderline Personality Disorder (BPD) who engage in non-suicidal self-injury (NSSI) report less pain in response to phasic nociceptive stimuli. In comparing an invasive pain stimulus to phasic nociceptive stimuli in BPD patients, the "blade" as non-invasive surrogate model for sharp mechanical pain in psychiatric patients is used. In contrast to healthy volunteers, BPD patients do not report significant affective ratings and specifically display a reduced sensory component for sharpness.

Posterior Insular GABA Levels Inversely Correlate with the Intensity of Experimental Mechanical Pain in Healthy Subjects.

This study aimed to investigate the relation of GABA and glutamate levels in the posterior insula and mechanical pain sensitivity in healthy subjects. Nineteen healthy female individuals underwent single voxel magnetic resonance spectroscopy (MRS) at 3 T. Metabolites were measured in the right posterior insula using MEGA-PRESS spectral editing. Mechanical pain sensitivity was experimentally assessed with pinprick stimuli on a numeric rating scale. Ratings of perceived intensity of 256 mN and 512 mN pinprick stimuli were negatively correlated with GABA levels and positively with glutamate levels in the posterior insula. Pinprick pain ratings were also positively correlated with the glutamate/GABA ratio. No significant correlation for pinprick stimuli of lower forces than 256 mN was observed. The results of our study support the hypothesis that excitatory and inhibitory neurotransmitter levels and/or the ratio of glutamate/GABA levels in the posterior insula are related to individual differences in pain sensitivity. These results are in line with chronic pain studies, where elevated glutamate/GABA ratios in the insular cortex of patients with chronic pain syndromes were observed.

A novel human surrogate model of noninjurious sharp mechanical pain.

We propose a blade as a noninjurious nociceptive stimulus modeling sharp mechanical pain and yielding acute pain and hyperalgesia responses with closer proximity to incision-induced pain/hyperalgesia than punctate or blunt pressure mechanical pain models. Twenty-six healthy men and women were investigated to compare a small incision in the left forearm with noninvasive stimuli of different shapes and modalities to the right forearm. The magnitude and time course of incisional and blade-induced pain were assessed by numerical rating scales. Affective vs sensory components of pain experience were differentiated using a pain sensation questionnaire. The magnitude and time course of the axon reflex vasodilator response and of secondary hyperalgesia following a 7-second blade application were assessed. The maximum blade or incisional pain was similar (visual analogue scale [mean ± SD]: 32.9 ± 22.5 [blade] vs. 33.6 ± 29.8 [incision]), and both time courses matched closely in the first 10 seconds (paired t test; P = 0.5-1.0), whereas incision but not blade was followed by a second phase of pain, probably related to the tissue injury (decrease to half maximum pain 8 ± 2 vs. 33 ± 35 seconds; P < 0.01). Affective pain scores were significantly lower than sensory scores for all stimuli (P < 0.001). Comparing blade and incision, patterns of affective and sensory pain descriptors exhibited a remarkably similar pattern. Hence, we suggest the blade as novel model of sharp mechanical pain, which will be useful in investigating postoperative/mechanical pain and the role of self-injurious behavior in, eg, patients with borderline personality disorder.