Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation.

Objective: This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. Methods: The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days. Results: pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. Conclusion: pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

ET-B receptors involvement in peripheral opioid analgesia induced by light-emitting diode photobiomodulation in male and female mice.

Currently, photobiomodulation therapy (PBMT) is gaining space in the scientific and clinical environment. To help elucidate the importance of irradiance, this study evaluated the effect of two different PBMT irradiances (3.5 and 90 mW/cm2), given a fixed wavelength of 630 nm and a dose of 2 J/cm2, on mechanical hyperalgesia following Complete Freund's Adjuvant (CFA) intraplantar (i.pl.) injection in mice. Additionally, we investigated the role of peripheral opioid and endothelin-B receptors (ETB-R), as well as sex differences in treatment outcome. Different groups of male or female mice were evaluated 6 and 96 h after CFA. Mechanical hyperalgesia was evaluated 30 min after treatments. Naloxone or Bq-788 administration, fifteen minutes before PBMT or Sarafotoxin S6c, helped determine the involvement of peripheral opioid and ETB-Rs on PBMT. Lastly, ETB-Rs skin immunocontent in both sexes was quantified after PBMT consecutive daily treatments. PBMT at an irradiance of 90 mW/cm2, was more effective than 3.5 mW/cm2. Bq-788 and naloxone administration prevented the effects of PBMT and SRTX S6c; however, PBMT did not influence peripheral ETB-Rs immunocontent. The results suggest that irradiance influences PMBT effect; and that activation of ETB-R play a role in peripheral PBMT opioid induced analgesia. Lastly, PMBT effects do not appear to be sex-dependent.

Balneotherapy decreases mechanical hyperalgesia by reversing BDNF and NOS2 immunocontent in spinal cord of mice with neuropathic pain.

In the last decades, balneotherapy or thermalism has been used for health promotion and in the treatment of inflammatory and chronic processes. We found that balneotherapy reduced mechanical hyperalgesia, as well the increase of BDNF and NOS2 levels in the spinal cord, while increased BDNF and NOS1 in the paw. The data presented herein demonstrated for the first time in a murine model of neuropathic pain, the analgesic effect of balneotherapy with the water from the natural springs of Santo Amaro da Imperatriz-Brazil. Nevertheless, future clinical trials should be conducted to test the effectiveness of balneotherapy in neuropathic pain patients.

Foot Reflexotherapy Induces Analgesia in Elderly Individuals with Low Back Pain: A Randomized, Double-Blind, Controlled Pilot Study.

INTRODUCTION: This study evaluated the effects of foot reflexotherapy on pain and postural balance in elderly individuals with low back pain. DESIGN: Randomized, controlled pilot study. Participants (n = 20) were randomly assigned to 2 groups: individuals submitted to conventional foot massage (control group) or foot reflexotherapy (RT, intervention group) for a period of 5 weeks. Questionnaires on pain and disability (visual analogue scale [VAS] and Roland-Morris Disability Questionnaire [RMDQ]), heart rate variability, and orthostatic balance and baropodometric analysis were assessed at two intervals: before and after intervention. RESULTS: RT group showed statistically significant differences when compared to control group in the following parameters: decrease in VAS scores for pain throughout the study, decrease in parasympathetic activity, and improvement in RMDQ scores. The two groups did not statistically differ in either orthostatic balance or baropodometric analyses. CONCLUSION: This study demonstrated that foot reflexotherapy induced analgesia but did not affect postural balance in elderly individuals with low back pain.