Neural mobilization reverses behavioral and cellular changes that characterize neuropathic pain in rats

Fabio M Santos, Joyce T Silva, Aline C Giardini, Priscila A Rocha, Arnold P P Achermann, Adilson S Alves, Luiz R G Britto, Marucia Chacur, Fabio M Santos, Joyce T Silva, Aline C Giardini, Priscila A Rocha, Arnold P P Achermann, Adilson S Alves, Luiz R G Britto, Marucia Chacur

Abstract

Background: The neural mobilization technique is a noninvasive method that has proved clinically effective in reducing pain sensitivity and consequently in improving quality of life after neuropathic pain. The present study examined the effects of neural mobilization (NM) on pain sensitivity induced by chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted thereafter to 10 sessions of NM, each other day, starting 14 days after the CCI injury. Over the treatment period, animals were evaluated for nociception using behavioral tests, such as tests for allodynia and thermal and mechanical hyperalgesia. At the end of the sessions, the dorsal root ganglion (DRG) and spinal cord were analyzed using immunohistochemistry and Western blot assays for neural growth factor (NGF) and glial fibrillary acidic protein (GFAP).

Results: The NM treatment induced an early reduction (from the second session) of the hyperalgesia and allodynia in CCI-injured rats, which persisted until the end of the treatment. On the other hand, only after the 4th session we observed a blockade of thermal sensitivity. Regarding cellular changes, we observed a decrease of GFAP and NGF expression after NM in the ipsilateral DRG (68% and 111%, respectively) and the decrease of only GFAP expression after NM in the lumbar spinal cord (L3-L6) (108%).

Conclusions: These data provide evidence that NM treatment reverses pain symptoms in CCI-injured rats and suggest the involvement of glial cells and NGF in such an effect.

Figures

Figure 1
Figure 1
Effect of neural mobilization on pain threshold induced by CCI in rats. Pain thresholds as measured by the test of Randall & Selitto (A), von frey test (B), expressed in grams, and thermal hyperalgesia, assessed by Hargreaves test (C), expressed in seconds. Measurements were determined before (base line- BL), 14 days after and at different intervals after NM sessions. The results represent the mean ± SEM of 10 animals per group. * P <0.05 for comparison between groups: CCI and CCI NM.
Figure 2
Figure 2
Densitometric analysis of NGF protein levels in the DRG (A) and spinal cord (B). The normalized average between sham and experimental groups (CCI) is reported. Data for naive animals were taken as 100%. Data are reported as mean ± SEM of 6 animals per group. * P <0.05 compared to CCI animals.
Figure 3
Figure 3
Densitometric analysis of GFAP protein levels in the DRG (A) and spinal cord (B). The normalized average between sham and experimental groups (CCI) is reported. Data for naive animals were taken as 100%. Data are reported as mean ± SEM of 6 animals per group. * P <0.05 compared to CCI animals.
Figure 4
Figure 4
Double-labeling of NGF and NeuroTrace in the ipsilateral DRG after CCI injury. Naive, Sham (control), CCI (14 days after injury) and animals treated with neural mobilization (CCI NM) were analyzed. Double immunofluorescence shows NGF (red) and NeuroTrace (green). Note that NGF expression after neural mobilization decreased when compared to CCI. Scale bar, 50 μm.
Figure 5
Figure 5
Double-labeling of GFAP and NeuroTrace in the ipsilateral DRG after CCI injury. Naive, Sham (control), CCI (14 days after injury) and animals treated with neural mobilization (CCI NM) were analyzed. Double immunofluorescence shows GFAP (red) and NeuroTrace (green). Note that GFAP expression after neural mobilization decreased when compared to CCI. Scale bar, 100 μm.

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