Bodily Sensory Inputs and Anomalous Bodily Experiences in Complex Regional Pain Syndrome: Evaluation of the Potential Effects of Sound Feedback

Neuroscientific studies have shown that human's mental body representations are not fixed but are constantly updated through sensory feedback, including sound feedback. This suggests potential new therapeutic sensory approaches for patients experiencing body-perception disturbances (BPD). BPD can occur in association with chronic pain, for example in Complex Regional Pain Syndrome (CRPS). BPD often impacts on emotional, social, and motor functioning. Here we present the results from a proof-of-principle pilot study investigating the potential value of using sound feedback for altering BPD and its related emotional state and motor behavior in those with CRPS. We build on previous findings that real-time alteration of the sounds produced by walking can alter healthy people's perception of their own body size, while also resulting in more active gait patterns and a more positive emotional state. In the present study we quantified the emotional state, BPD, pain levels and gait of twelve people with CRPS Type 1, who were exposed to real-time alteration of their walking sounds. Results confirm previous reports of the complexity of the BPD linked to CRPS, as participants could be classified into four BPD subgroups according to how they mentally visualize their body. Further, results suggest that sound feedback may affect the perceived size of the CRPS affected limb and the pain experienced, but that the effects may differ according to the type of BPD. Sound feedback affected CRPS descriptors and other bodily feelings and emotions including feelings of emotional dominance, limb detachment, position awareness, attention and negative feelings toward the limb. Gait also varied with sound feedback, affecting the foot contact time with the ground in a way consistent with experienced changes in body weight. Although, findings from this small pilot study should be interpreted with caution, they suggest potential applications for regenerating BDP and its related bodily feelings in a clinical setting for patients with chronic pain and BPD

Number of viable cells in samples treated with the various APs / AP-based reagents alone (grey bars: AP-7, AP-8, AP-11, AP-15, AP-15/DOPE, AP-15/DOPE/DMEM) and AP:pGFP / AP-15 and DOPE-containing complexes (patterned bars: AP:pGFP: AP-7, AP-8, AP-11 r = 1.7, AP-15 r = 2.0; AP-15/DOPE:pGFP, AP-15/DOPE/DMEM:pGFP 2.5 μg of lipids/μg of pDNA), analysed by FACS.

<p>Transfections were performed with the use of 4 μg of pDNA. *P<0.05.</p

Evaluation of transfection efficiency of B16-F10 cells transfected with use of carrier:pDNA complexes.

<p>(a) Percentage of GFP-positive cells transfected with complexes: AP:pGFP at different N/P ratios (r = 1.7 for AP-7, AP-8, AP-11, r = 2.0 for AP-15) and AP-15/DOPE:pGFP, AP-15/DOPE/DMEM:pGFP lipoplexes containing 2.5 μg of lipids/μg of pGFP, analysed by FACS; Ap- significant difference from AP-15 treatment, At- significant difference from Attractene treatment, L- significant difference from Lipofectamine treatment, P- significant difference from PEI treatment, (b) Activity of β-galactosidase in cells transfected with complexes: AP-11:pLacZ, AP-15:pLacZ, PEI:pLacZ, at r = 2.0–2.5 N/P ratio, studied by β-Gal test; *P<0.05, **P<0.005. Transfections were performed using 4 μg of respective pDNA.</p

Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.

<p>Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.</p

<i>In vivo</i> transfection study of tumor cells using AP-15-based complexes.

<p>Analyses of PCR products using DNA templates from: (a) B16-F10 tumors, injected with: 2-4- H₂O, 5-7- AP-15/DOPE, 8-10- AP-15, 11-13- pSec, 14-16- pTIMP2, 17-20- AP-15/DOPE:pTIMP2 complexes, 21-24- AP-15:pTIMP2 complexes; 25- positive control for PCR (pTIMP2), (b) L1 tumors, injected with: 2-3- H₂O, 4-5- AP-15, 6-7- AP-15/DOPE/DMEM, 8-14- AP-15:pTIMP2 complexes, 15-21- AP-15/DOPE/DMEM:pTIMP2 complexes; 25- positive control for PCR (pTIMP2). M- molecular weight size marker 1kb+, 1- reagent control for PCR.</p

Gel retardation analysis with different carrier:pDNA complexes at various N/P ratios (of amino-group of the carriers to the phosphate group of the nucleic acid).

<p>(a) AP-11:pDNA, (b) AP-15:pDNA, (c) AP-7:pDNA, (d) AP-8:pDNA, (e) PEI:pDNA. M- molecular weight size marker 1kb+.</p

Effect of transfection of B16-F10 cells with AP-15/DOPE:pDNA complexes on expression of lipid metabolism-related gene.

<p>Effect of transfection of B16-F10 cells with AP-15/DOPE:pDNA complexes on expression of lipid metabolism-related gene.</p

TIMP2 protein expression in B16-F10 cells assessed by Western blot in.

<p>(a) cell lysates, (b) media from cells. (c) Control Gapdh protein level in cell lysates. Lines: 1- B16-F10 cells, 2- B16-F10 cells transfected with AP-15/DOPE:pGFP, 3- B16-F10 cells transfected with AP-15/DOPE:pTIMP2.</p

(a) cell viability and (b) total cell number of B16-F10 cells transfected with AP:pGFP complexes at various N/P ratios (r = 1.7 for AP-7, AP-8, AP-11, r = 2.0 for AP-15), or with AP-15/DOPE:pGFP and AP-15/DOPE/DMEM:pGFP lipoplexes at 2.5 μg of lipids/μg of pDNA dose, analysed by FACS.

<p>Transfections were performed with the use of 4 μg of pDNA. *P<0.05, **P<0.001.</p