Iraci Lucena da Silva Torres (UFRGS)
Professor at the Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Lecture: Long-lasting effect of transcranial direct current stimulation (tDCS) in the reversal of hyperalgesia and cytokine alterations induced by the neuropathic pain model.
Abstract: Background: neuropathic pain (NP) is caused by an insult or dysfunction in the peripheral or central nervous system (CNS), the main symptoms being mechanical allodynia and hyperalgesia. NP often shows insufficient response to classic analgesics and its management remains a challenge. Associated to great development of pharmacological therapies to assist in pain relief, studies have been undertaken to identify methods of central stimulation that can contribute in pain management. In this way, transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation with low cost and represents a promising resource for pain management. Objective: to evaluate the effect of exposure to repeated transcranial direct current stimulation (tDCS) in the anti-nociceptive and anti-inflammatory response of rats submitted to neuropathic pain models developing a safer and more effective treatment for chronic pain. Methods: the animals were exposed to chronic constriction injury of infraorbital nerve (CCI- ION) surgery or to chronic constriction injury of sciatic nerve (CCI-SN) to induce neuropathic pain. The bimodal tDCS (0.5mA) was applied for 20min/day/8days. For the CCI-ION model, facial allodynia was assessed via filament von Frey test at baseline, 3, 7, 10 and 14 after surgery and also immediately and 24 hours after the end of treatment. For both experiments, the rats were killed by decapitation 48 hours or 7 days after treatment completion. In the CCI-SN model, the nociceptive response was assessed by the hot plate and von Frey tests and evaluated at baseline, 7 days, and 14 days after surgery, and also immediately, 24 hours, and 7 days following tDCS treatment. Were performed biochemical analysis for both models: in the CCI-ION model we analyzed the brainstem NGF, TNF-α, interleukin 10 levels, and serum LDH levels and in the CCI-SN the levels of IL-1β, IL-10 and TNF-α in the cortex, spinal cord, and brainstem by ELISA at 48 hours and 7 days post-tDCS. Results: the chronic constriction injury models provoked nociceptive behaviors until at least 30 days post-surgery; however, bicephalic tDCS relieved the nociceptive behavior for up to 7 days after treatment completion. In the CCI-ION model, was observed an interaction between the variables pain model and treatment in brainstem levels of NGF, TNF-α and IL-10. The CCI-SN model induced an increase in the levels of IL- 1 β and IL-10 in the CNS and those increases were totally reversed by bicephalic tDCS only in the spinal cord. Furthermore, the bicephalic tDCS plus NP modality increased TNF-α levels in the cerebral cortex and spinal cord only at 7 days after the end of tDCS sessions. Conclusions: in summary, our findings demonstrated that bicephalic tDCS is effective to promote antinociceptive behavior in neuropathic pain, which can be reflected by a spinal neuroimmunomodulation linked to pro- and anti-inflammatory cytokine levels observed in the long-term. In addition, we noted an important role of the central immune system in the neuropathic process, which can be implicated in maladaptive neuroplastic changes. Considering those alterations, to achieve a lasting benefit with a nonpharmacological and noninvasive treatment, this intervention should be able to modulate the entire signaling pathway.