Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis - PubMed (original) (raw)

Randomized Controlled Trial

. 2015 Nov;135(11):2623-2631.

doi: 10.1038/jid.2015.233. Epub 2015 Jun 22.

Laura Cornelissen 2, William Sipprell 3, Joachim Pruessner 3, Sarina Elmariah 4, Tuan Luo 4, Ethan A Lerner 4, Yookyung Jung 3, Conor Evans 3, David Zurakowski 2, Charles B Berde 2, R Rox Anderson 3

Affiliations

Randomized Controlled Trial

Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis

Lilit Garibyan et al. J Invest Dermatol. 2015 Nov.

Abstract

Cryolipolysis is a noninvasive, skin cooling treatment for local fat reduction that causes prolonged hypoesthesia over the treated area. We tested the hypothesis that cryolipolysis can attenuate nociception of a range of sensory stimuli, including stimuli that evoke itch. The effects of cryolipolysis on sensory phenomena were evaluated by quantitative sensory testing (QST) in 11 healthy subjects over a period of 56 days. Mechanical and thermal pain thresholds were measured on treated and contralateral untreated (control) flanks. Itch duration was evaluated following histamine iontophoresis. Unmyelinated epidermal nerve fiber and myelinated dermal nerve fiber densities were quantified in skin biopsies from six subjects. Cryolipolysis produced a marked decrease in mechanical and thermal pain sensitivity. Hyposensitivity started between two to seven days after cryolipolysis and persisted for at least thirty-five days post treatment. Skin biopsies revealed that cryolipolysis decreased epidermal nerve fiber density, as well as dermal myelinated nerve fiber density, which persisted throughout the study. In conclusion, cryolipolysis causes significant and prolonged decreases in cutaneous sensitivity. Our data suggest that controlled skin cooling to specifically target cutaneous nerve fibers has the potential to be useful for prolonged relief of cutaneous pain and might have a use as a research tool to isolate and study cutaneous itch-sensing nerves in human skin.

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Conflict of interest statement

Conflict of interest statement: RRA receives a portion of royalties paid to Massachusetts General Hospital by Zeltiq, according to institutional policies. The remaining authors state no conflict of interest.

Figures

Figure 1

Figure 1. Experimental time line

Experiments were performed in the test-order listed. Arrows indicate time-point each experiment was performed.

Figure 2

Figure 2. Cryolipolysis reduces cutaneous sensitivity to mechanical and thermal stimuli following cryolipolysis

Sensory threshold for Control side shown in white bars and Treatment side shown in grey bars. (a and b) Mechanical pain threshold (MPT); (c and d) Cold detection threshold (CDT); (e and f) Vibration detection threshold (VDT); (g and h) Warmth detection threshold (WDT). Data for each side is compared to baseline sensory threshold. MPT data: bars represent median; whiskers represent LQ to UQ; p-values determined from Wilcoxon Signed Ranks Test. VDT, WDT, and CDT data: bars represent mean; whiskers represent 95% CI; p values determined from Mixed Model Repeated Measures ANOVA with Bonferroni correction (assuming significance at p<0.05). Asterisks indicate level of significance compared to Treatment baseline: *, p<0.05; **, p<0.01, ***, p<0.005. Crosses (+) indicate level of significance compared to Control baseline (+ p=<0.05, +++p=<0.001). BL, Baseline.

Figure 3

Figure 3. Cryolipolysis reduces epidermal nerve fiber density and myelinated dermal fiber density

(a) Density of epidermal nerve fibers (ENF), (b) Density of myelinated dermal nerve fibers. Data shown as mean (SD). P-values determined using mixed model repeated measures ANOVA with Bonferroni correction. Asterisks indicate level of significant compared to baseline. *, p<0.05.

Figure 4

Figure 4. Confocal microscopy imaging of biopsy samples

(a) A single biopsy sample demonstrating the confocal imaging technique. The entire 3 mm skin biopsy specimen with 70 μm thickness was imaged every 2 μm. Frames were stacked to create a 3D projection of each confocal image. Thirty-five frames per biopsy were generated and then stitched together using custom-built routines in ImageJ/Fiji. (b) 3D projection of confocal image. The green channel representing fibers stained with anti-PGP9.5 was used to quantify epidermal nerve fibers, and the red channel representing fibers stained with anti-MBP antibody was used to quantify the dermal myelinated fibers. Scale bar = 250 μm

References

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