Stefania Giotti Cioato1, Liciane Fernandes Medeiros2, Paulo Ricardo Marques Filho1, Rafael Vercelino3, Andressa de Souza1, Vanessa Leal Scarabelot3, Carla de Oliveira1, Lauren Naomi Spezia Adachi1, Felipe Fregni4, Wolnei Caumo1, Iraci L S Torres5. 1. Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil. 2. Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil. 3. Graduate Program in Biological Sciences - Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil. 4. Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States. 5. Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Graduate Program in Biological Sciences - Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil. Electronic address: iracitorres@gmail.com.
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. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management. OBJECTIVE/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management. OBJECTIVE/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Daniela Silva Santos; Bettega Costa Lopes; Liciane Fernandes Medeiros; José Antônio Fagundes Assumpção; Andressa de Souza; Artur Alban Salvi; Lisiane Santos da Silva; Felipe Fregni; Wolnei Caumo; Iraci L S Torres Journal: Neurochem Res Date: 2020-08-25 Impact factor: 3.996