The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain

Fabio Martinez Santos, Leandro Henrique Grecco, Marcelo Gomes Pereira, Mara Evany Oliveira, Priscila Abreu Rocha, Joyce Teixeira Silva, Daniel Oliveira Martins, Elen Haruka Miyabara, Marucia Chacur, Fabio Martinez Santos, Leandro Henrique Grecco, Marcelo Gomes Pereira, Mara Evany Oliveira, Priscila Abreu Rocha, Joyce Teixeira Silva, Daniel Oliveira Martins, Elen Haruka Miyabara, Marucia Chacur

Abstract

Background: The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats.

Methods: The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system.

Results: An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG.

Conclusion: These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation.

Figures

Figure 1
Figure 1
Analysis of Sciatic Functional Index (SFI). Motor dysfunction was induced by chronic constriction injury (CCI) to the sciatic nerve. Functional assessment was evaluated, 14 days after injury (14d PO), after the third (3°s); seventh (7°s); and tenth (10°s) session (s) using the SFI. The results obtained are expressed as a percentage of normal function, where 0 (zero) corresponds to normal function or no disability and -100 (minus one hundred) corresponds to total dysfunction. The results are expressed as the mean ± S.E.M. Five animals per group. *p <0.05 per CCI comparison group. #p <0.05 compared to the CCI NM group and p <0.05 compared to the initial measurement.
Figure 2
Figure 2
Analysis of in vivo muscle function experiments. The results are expressed in grams. The results are expressed as the mean ± S.E.M. n = 5. **p <0.001 comparing the CCI and control groups (naive, sham and sham NM) *p <0.001 comparing the CCI NM and CCI groups.
Figure 3
Figure 3
Densitometry analysis of DOR (A), KOR (B) and MOR (C) expression in the periaqueductal gray after CCI injury. The normalized average between sham and experimental groups (CCI) is reported. Values measured for naive animals were considered 100%. Data are reported as the mean ± SEM of 6 animals per group. A) *p < 0.001 comparing the CCI group with the naive group. B) *p < 0.05 the CCI group with naive animals, **p < 0.001 comparing the CCI NM group with the other groups.

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