Transcranial direct current stimulation alleviates nociceptive behavior in male rats with neuropathic pain by regulating oxidative stress and reducing neuroinflammation

Abstract

Transcranial direct curent stimulation (tDCS) and trans‐spinal direct current stimulation (tsDCS) are promising therapies for pain that can alter the excitability of neuronal activity in cerebral cortex. The aim of the study is to investigate the therapeutic effects of direct current stimulation (DCS) over the spinal cord and cerebral cortex on oxidative stress and neuroinflammation in rats with chronic constriction injury (CCI). Male Wistar rats were randomly divided into four experimental groups: Sham, CCI, CCI + tDCS and CCI + tsDCS. The neuropathic pain model was induced by using the CCI model. Rats with neuropathy were treated with cathodal tDCS and tsDCS stimulations consisting of 0.5 mA for 30 min a day for 7 days from day 8 onwards. Locomotor activity was measured by open‐field test and nociceptive behavior was assessed by hot‐plate, tail‐flick and Randall–Selitto tests. Following the behavioral experiments, total oxidant capacity (TOC), total antioxidant capacity (TAC) and proinflammatory cytokine levels were evaluated in spinal cord and cerebral cortex tissues. The CCI model induced significant mechanical and thermal hyperalgesia. Nociceptive behaviors in rats with CCI were reversed by DCS treatment. Higher TOC and lower TAC levels were detected in the spinal cord and cerebral cortex tissues of the CCI rats compared to the control. tsDCS treatment amended oxidant/antioxidant status. Moreover, tsDCS modulated the central levels of Tumor necrosis factor‐α (TNF‐α), interleukin 1‐beta (IL‐1β), IL‐6 and IL‐18. tsDCS stimulation showed better therapeutic effect on neuropathic pain by regulating oxidant/antioxidant levels and reducing neuroinflammation. DCS, especially at spinal level, may be a promising therapeutic strategy that can be used alone or in combination with other effective treatments for alleviating neuropathic pain.

[6]-Shogaol and [6]-Gingerol active ingredients may improve neuropathic pain by suppressing cytokine levels in an experimental model

“…In contrast, we observed that 200 mg/kg ginger treatment improved both locomotor activity and thermal allodynia. NP begins to occur on the 7th day after surgery in animals with nerve damage [ 2 ]. Borgonetti et al started treatment on day 3 after surgery, whereas we started the ginger treatment on the 7th day after surgery and applied it for 7 days; this might explain the different results for improvement in locomotor activity.…”

“…Proinflammatory cytokines are important in the development and maintenance of NP [ 44 ]. NP is characterised by glial cell activation and proinflammatory cytokine secretion in the spinal dorsal horn [ 2 ]. TNF-α is one of the most potent proinflammatory cytokines expressed by microglia, astrocytes, and primary sensory dorsal root ganglion neurons [ 45 ].…”

“…Neuropathic pain (NP) is a type of chronic pain that is usually caused by damage to the somatosensory system [ 1 ]. Approximately 20% of the adult population worldwide suffers from chronic pain each year [ 2 ], and neuroinflammation has an important role in the development of chronic pain. Neuroinflammation is also an underlying cause of many central nervous system (CNS) diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and psychiatric disorders [ 3 ].…”