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.

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.

In this study, we investigated age and sex differences in acute and chronic pain in rats. Groups of young (3–6 months) and aged (20–24 months) male and female Fischer 344 rats were used to assess basal thermal and mechanical thresholds, capsaicin-induced acute nocifensive responses and c-Fos expression in the spinal cord, and monoiodoacetate (MIA)-induced knee osteoarthritis (OA)-like pain responses. There was a significant sex, but not age, effect on thermal threshold on the hindpaw and mechanical threshold on the knee joint. No significant age and sex differences in capsaicin-induced nocifensive and c-Fos responses were observed. MIA induced a greater peak reduction of weight-bearing responses in aged males than young rats. Aged females developed the most profound weight-bearing deficit. With knee joint sensitivity as a primary outcome measure, MIA induced more pronounced and longer-lasting hyperalgesia in older rats, with aged female rats showing the worst effect. These data suggest that age may not have significant effect on acute nociceptive processing, but it significantly impacts OA-like pain, making aged rats, especially females, more vulnerable to chronic pain conditions. These preclinical models should provide important tools to investigate basic mechanisms underlying the impact of age and sex in chronic pain conditions.

Neuroimaging of pain in animals allows us to better understand mechanisms of pain processing and modulation. In this review, we discuss recently published brain imaging studies in rats, mice, and monkeys, including functional magnetic resonance imaging (MRI), manganese-enhanced MRI, positron emission tomography, and electroencephalography. We provide an overview of innovations and limitations in neuroimaging techniques, as well as results of functional brain imaging studies of pain from January 1, 2016, to October 10, 2018. We then discuss how future investigations can address some bias and gaps in the field. Despite the limitations of neuroimaging techniques, the 28 studies reinforced that transition from acute to chronic pain entails considerable changes in brain function. Brain activations in acute pain were in areas more related to the sensory aspect of noxious stimulation, including primary somatosensory cortex, insula, cingulate cortex, thalamus, retrosplenial cortex, and periaqueductal gray. Pharmacological and nonpharmacological treatments modulated these brain regions in several pain models. On the other hand, in chronic pain models, brain activity was observed in regions commonly associated with emotion and motivation, including prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, basal ganglia, and nucleus accumbens. Neuroimaging of pain in animals holds great promise for advancing our knowledge of brain function and allowing us to expand human subject research. Additional research is needed to address effects of anesthesia, analysis approaches, sex bias and omission, and potential effects of development and aging.