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. 2022 Nov 18;12(1):19891.
doi: 10.1038/s41598-022-24178-6.

Fast-acting and injectable cryoneurolysis device

Sara Moradi Tuchayi  1   2 , Ying Wang  1   2 , Alla Khodorova  1   2 , Isaac J Pence  1   2 , Anat Stemmer-Rachamimov  2   3 , Conor L Evans  1   2 , R Rox Anderson  1   2 , Lilit Garibyan  4   5
Affiliations

Fast-acting and injectable cryoneurolysis device

Sara Moradi Tuchayi et al. Sci Rep. .

Abstract

Cryoneurolysis is an opioid-sparing therapy for long-lasting and reversible reduction of pain. We developed a nerve-selective method for cryoneurolysis by local injection of ice-slurry (- 5 to - 6 °C) that induced decrease in nocifensive response starting from about a week after treatment and lasting up to 8 weeks. In this study, we test the hypothesis that injection of colder slurry leads to faster onset of analgesia. Colder slurry (- 9ºC) was injected around the rat sciatic nerve to induce cryoneurolysis. Hematoxylin and Eosin (H&E) staining was used to examine histologic effects on surrounding tissues. Coherent anti-Stokes Raman scattering (CARS) microscopy was used to study effects on myelin sheaths. Functional tests were used to assess changes in sensory and motor function in the treated hind paw. No inflammation or scarring was detected in surrounding skin and muscle tissues at day 7 post slurry injection. Functional tests showed rapid onset reduction in mechanical pain sensitivity starting from day 1 and lasting up to day 98. CARS imaging demonstrated disintegration of myelin sheaths post treatment followed by complete recovery of nerve structure by day 140. In this study we showed that colder slurry (- 9 °C) produces more rapid onset and longer duration of analgesia, while remaining nerve-selective.

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Conflict of interest statement

R.R.A, and L.G. are inventors in patents related to this work, which are owned by the Massachusetts General Hospital. R.R.A, L.G., S.M.T, and Y.W. hold equity in companies recently founded to develop and commercialize this technology. The company had no involvement in this study. C.L.E. is an inventor on patents related to coherent Raman imaging. Other authors do not have any conflict of interest.

Figures

Figure 1
Figure 1
Slurry is selective to nerve tissue with no damage to surrounding skin or muscle tissue. Representative images of (A) skin, and (B) muscle tissue at the injection site stained with H&E at 7 days after injection of slurry; scale bar, 100 μm; RT, room temperature.
Figure 2
Figure 2
Slurry shows rapid onset reduction in nerve function (A) Paw withdrawal frequency in response to stimulation with 15 g VFH force at different time points post slurry injection. (B) Effects of slurry injection on paw withdrawal latency in response to heat stimulation in treated hind limbs. (C) Toe spread and (D) walking scores of hind limbs treated with slurry. Data are presented as median with interquartile range. n = 9; * P < 0.05, ** P < 0.001 compared to baseline values by Friedman test followed by Dunn’s multiple comparisons test. (E) CARS microscopy images show myelin and nerve structure in sciatic nerve samples after injection of slurry and room temperature control solution. (F) Graph shows CCP index after injection of slurry and room temperature control solution. Data are presented as mean ± SD. n = 4 per group; * P < 0.0001 compared to baseline values by Ordinary one-way ANOVA followed by Tukey's multiple comparisons test; RT: room temperature.
See this image and copyright information in PMC

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