Effects of Fe²⁺ Nanoparticles on Pain Responses and Neural Oscillation Following Chronic Neuropathic Pain in Rats

Neuropathic pain, a chronic pain condition caused by nerve damage either of the peripheral or central nervous system, responds poorly to current drug treatments. The present study aimed to investigate the analgesic and anxiolytic effect of Fe²⁺ nanoparticles on chronic constriction injury of sciatic nerve (CCI)-induced neuropathic pain in rats. We also assessed the effects of Fe²⁺ nanoparticles on brain rhythmical oscillation in rats with neuropathic pain. The CCI model was induced by four loose ligations of the left sciatic nerve. Male Wistar rats were divided into four groups: control, sham, CCI, and CCI+Fe²⁺ nanoparticle (1 mg/kg). The Fe²⁺ nanoparticle was administered by gavage on the day of CCI surgery (day 0) and daily (once a day) for 21 consecutive days after CCI surgery. Behavioral studies were conducted on days -1, 3, 7, 14, and 21 after CCI. An acetone test and elevated plus maze were performed to evaluate cold allodynia and induced anxiety-like responses, respectively. A field test was conducted to evaluate innate anxiety-like behaviors. In addition, an electrophysiological study was carried out on day 21 after CCI to assess the effects of drugs on brain wave power. Application of Fe²⁺ significantly reduced cold allodynia in all tested days after CCI, compared to the CCI group. The obtained data demonstrated that Fe²⁺ nanoparticle gavage caused analgesic and anxiolytic effects on all experimental days after CCI, compared to the CCI group. The CCI surgery significantly disturbed theta, alpha, and beta power in the brain. The application of Fe²⁺ nanoparticles could not significantly change brain wave power. It is suggested that Fe²⁺ nanoparticle has analgesic and anxiolytic effects during chronic neuropathic pain in rats. Furthermore, the CCI surgery effectively disturbed brain theta, alpha, and beta power. Nonetheless, the application of Fe²⁺ nanoparticles could not change deregulated brain oscillation in rats.