Electroacupuncture decreases inflammatory pain through a pro-resolving mechanism involving the peripheral annexin A1-formyl peptide receptor 2/ALX-opioid receptor pathway.

The pro-resolving mechanism is a recently described endogenous process that controls inflammation. The present study evaluated components of this mechanism, including annexin 1 (ANXA1) and the formyl peptide receptor 2/ALX (FPR2/ALX) receptor, in the antihyperalgesic effect induced by electroacupuncture (EA) in an animal model of persistent peripheral inflammation. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2-10 Hz, ST36-SP6) or subcutaneous BML-111 injection (FPR2/ALX agonist) for 5 consecutive days. In a separate set of experiments, on the first and fifth days after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or naloxone (non-selective opioid receptor antagonist) before EA or BML-111 injection. Paw protein levels of FPR2/ALX and ANXA1 were evaluated on the second day after CFA injection by western blotting technique. EA and BML-111 reduced mechanical hyperalgesia. I.pl. naloxone or WRW4 prevented the antihyperalgesic effect induced by either EA or BML-111. EA increased ANXA1 but did not alter FPR2/ALX receptor levels in the paw. Furthermore, i.pl. pretreatment with WRW4 prevented the increase of ANXA1 levels induced by EA. This work demonstrates that the EA antihyperalgesic effect on inflammatory pain involves the ANXA1/FPR2/ALX pro-resolution pathway. This effect appears to be triggered by the activation of FPR2/ALX receptors and crosstalk communication with the opioid system.

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.