, 2003). Although the underlying mechanisms of long-lasting hyperalgesia after chronic stress are still elusive, some studies have advanced understanding of this topic. Human studies have shown that a reduction in pain threshold after long-term psychoemotional stress probably occurs due to a reduction

in the activity of the brain’s opioid system (Ashkinazi and Vershinina, 1999). Previous data from our group also suggest involvement of the opioid system in the hyperalgesic response induced by prolonged restraint stress (Torres et al., 2001b, Torres et al., 2003 and Dantas et al., 2005) Furthermore, activation of stress-related circuitry in the hypothalamus activates pain-facilitating neurons in the rostral ventromedial medulla to produce selleck products hyperalgesia (for review, see Martenson et al., 2009), suggesting possible changes in brain activity. Another possibility is increased expression of pro-inflammatory cytokines, such as interleukin-1β and tumor necrosis factor (TNFα), in brain tissue and blood due to stress conditions. These cytokines are closely related to painful and inflammatory diseases, and their release is increased under stressful conditions (for review, see Goshen and Yirmiya, 2009). In view of the neuroplastic effects of chronic stress on pain-related neural circuitry, deactivation of the stress-induced pain-related neural changes would be best achieved with techniques to induce neuroplasticity (Brunoni et

al., 2011). One simple but powerful technique www.selleckchem.com/products/VX-809.html is transcranial direct current stimulation (tDCS). This technique produces modulation of neural activity via small electrical currents that, when applied as a direct current (DC) component, polarize neural tissue, inducing significant changes in the resting membrane threshold (Zaghi, 2010) and subsequent changes in synaptic plasticity, as recently shown in an elegant animal model in mice brain slices DC stimulation (Fristch et al., 2010). In addition, it carries little risk

and produces little discomfort, and, with repeated sessions, may produce enduring effects (Poreisz et al., 2007). Previous studies have shown that excitability-enhancing anodal tDCS is effective in reducing pain in patients with fibromyalgia (Fregni et al., Progesterone 2006a) and spinal cord injury (Fregni et al., 2006b). In addition, anodal and cathodal tDCS of the primary motor cortex and dorsolateral prefrontal cortex have been associated with significant changes in experimental pain in healthy subjects (Reidler et al., 2012 and Grundmann et al., 2011) Finally, the neuromodulatory effects of tDCS have also been consistently demonstrated in animals, such as in rat models of focal epilepsy (Liebetanz et al., 2006), memory (Dockery et al., 2011), Parkinson’s disease (Li et al., 2011), and acute stroke (Wachter et al., 2011) Given the importance of chronic pain and the variability in its pathophysiology, investigation of techniques that can modulate neural mechanisms is relevant to the development of more rational therapies.