Long-Lasting Effect of Transcranial Direct Current Stimulation in the Reversal of Hyperalgesia and Cytokine Alterations Induced by the Neuropathic Pain Model.

Abstract

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. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management. We investigated the effects of tDCS on the nociceptive response and on IL-1β, IL-10, and TNF-α levels in CNS structures of rats with NP. After induction of NP by chronic constriction injury (CCI) of the sciatic nerve, the rats received 20 min of bicephalic tDCS for 8 days. Hyperalgesia was assessed by the hot plate and von Frey tests and evaluated at baseline, 7 days, and 14 days after CCI surgery, and also immediately, 24 hours, and 7 days following tDCS treatment. The levels of IL-1β, IL-10 and TNF-α in the cortex, spinal cord, and brainstem were determined by ELISA at 48 hours and 7 days post-tDCS. The CCI model provoked thermal and mechanical hyperalgesia until at least 30 days post-CCI; however, bicephalic tDCS relieved the nociceptive behavior for up to 7 days after treatment completion. 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.