Effects of photobiomodulation therapy on neuropathic pain in rats: evaluation of nociceptive mediators and infrared thermography.

Nerve injury induces release of peptides and upregulation of receptors such as substance P and transient receptor potential receptor V1 (TRPV1), which contribute to the development and maintenance of chronic pain. Photobiomodulation therapy (PBMT) is a nonpharmacological strategy that promotes tissue repair and reduces pain and inflammation. However, the molecular basis for PBMT effects on neuropathic pain is still unclear. We investigated the effects of PBMT on substance P, TRPV1, and superficial temperature change in a rodent model of neuropathic pain. We evaluated substance P and TRPV1 in dorsal root ganglia (DRG L4 to L6) at baseline, 14 days after chronic constriction injury (CCI) and after PBMT. We also assessed the superficial temperature of tarsal, metatarsal, tibia, and fibula regions before and after PBMT using infrared thermography. Substance P and TRPV1 levels increased in DRG of CCI rats compared to naive and sham rats and decreased after PBMT. Infrared thermography showed increased temperature of tarsal, metatarsal, tibia, and fibula regions in CCI rats, which was decreased after PBMT. There were no statistical differences between CCI rats with PBMT, sham, and naive rats in any assay. PBMT reduces nociceptive mediators and hind paw and leg's temperature in a rodent model of neuropathic pain, suggesting that PBMT may play a modulatory role in thermoregulation, neurogenic inflammation, and thermal sensitivity in peripheral nerve injuries. Therefore, PBMT appears to be a valuable strategy for neuropathic pain treatment in clinical settings.

Neural mobilization promotes nerve regeneration by nerve growth factor and myelin protein zero increased after sciatic nerve injury.

Neurotrophins are crucial in relation to axonal regrowth and remyelination following injury; and neural mobilization (NM) is a noninvasive therapy that clinically is effective in neuropathic pain treatment, but its mechanisms remains unclear. We examined the effects of NM on the regeneration of sciatic nerve after chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted to 10 sessions of NM, starting 14 days after CCI. Then, the nerves were analyzed using transmission electron microscopy and western blot for neural growth factor (NGF) and myelin protein zero (MPZ). We observed an increase of NGF and MPZ after CCI and NM. Electron microscopy revealed that CCI-NM samples had high numbers of axons possessing myelin sheaths of normal thickness and less inter-axonal fibrosis than the CCI. These data suggest that NM is effective in facilitating nerve regeneration and NGF and MPZ are involved in this effect.

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.

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.

Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats.

Background. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF) released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM) technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI). CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP), microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry. Conclusions. These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.