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. 2021 Apr 14;12:632028. doi: 10.3389/fphar.2021.632028

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Copyright © 2021 Renno, Afzal, Paul, Nair, Kumar and Al-Hassan.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A): Bar graphs showing tactile allodynia. The CRUSH and the CRUSH + SP-FB-treated groups showed a significant decrease in analgesia planter test at week 1 post-injury. By week 3, the CRUSH, CRUSH + 1X SPF-FB (S.C.) and CRUSH + 1X SPF-FB (IP) groups displayed an increase in analgesia. However, CRUSH + 0.5X SPF-FB (IP) group showed a significant decrease compared to CRUSH and CRUSH + SPF-FB S.C.-treated animals. The CRUSH + 0.5X SPF-FB (IP) stayed significantly different from the CRUSH group at week 5 following nerve injury. * indicates p < 0.0001 NAÏVE and SHAM vs. CRUSH, CRUSH + 0.5X SPF-FB (IP) and CRUSH + 1X SPF-FB (S.C.); ^α indicates p < 0.02 CRUSH + 0.5X SPF-FB (IP) vs. CRUSH; Ψ indicates p < 0.0001 CRUSH vs. NAÏVE, SHAM, and treated groups; Φ indicates p < 0.05 CRUSH + 1X SPF-FB (S.C.) vs. CRUSH; ¥ indicates p < 0.02 CRUSH vs. NAÏVE, SHAM and CRUSH + 0.5X SPF-FB (IP). (B): The CRUSH + SPF-FB-treated groups showed a significant decrease in paw withdrawal reflex latency periods compared with the CRUSH group at week 4. At week 6, CRUSH + 0.5X SPF-FB(IP)-treated animals displayed a significant decrease in paw pressure latency. * indicates p < 0.0001 NAÏVE and SHAM vs. Crush and treated groups; α indicates p < 0.0001 CRUSH vs. CRUSH + 0.5X SPF-FB (IP); Φ indicates p < 0.01 CRUSH vs. CRUSH + 1X SPF-FB (S.C.); Ψ indicates p < 0.0001 CRUSH vs. NAÏVE, SHAM and CRUSH + 0.5X SPF-FB (IP). (C): Nerve crush injury produced a severe nociception deficit in the CRUSH and CRUSH-SPF-FB-treated groups at week two following nerve injury. The CRUSH- SPF-treated groups showed a significant thermal nociceptive recovery starting at Week 4. At Week 6 post-injury, the CRUSH + 0.5X SPF-FB (IP) animals maintained the thermal nociception recovery comparable to control groups. * indicates p < 0.0001 NAÏVE and SHAM vs. CRUSH and CRUSH + SPF-FB-treated groups; α indicates p < 0.0001 CRUSH vs. NAÏVE, SHAM and CRUSH + SPF-treated groups; ¥ indicates p < 0.005 CRUSH + 0.5X SPF-FB(IP) vs. SHAM and CRUSH; Ψ indicates p < 0.01 CRUSH + 1X SPF-FB(S.C.) vs. NAÏVE and SHAM groups; # indicates p < 0.001CRUSH vs. NAÏVE, SHAM and treated groups. (D): The CRUSH + 0.5X SPF-FB-treated group showed significant tail-flick withdrawal latency recovery compared CRUSH group by the end of week 4 post-surgery. This nociception normalization was sustained until the end of the experiment, whereas CRUSH animals continued to display a significant increase in the tail-flick withdrawal latency compared to controls and SPF-FB-treated groups. * indicates p < 0.01 CRUSH vs. all groups; α indicates p < 0.01 SHAM vs. CRUSH + 0.5X SPF-FB(IP) and CRUSH + 1X SPF-FB(S.C.); Ψ indicates p < 0.001 CRUSH vs. CRUSH + SPF-FB-treated groups; # indicates p < 0.0001 CRUSH vs. all groups. All values are expressed as means ± SDs (error bars).