Implication of long term Nicotine exposure on pain hypersensitivity and cognitomotor functions following repetitive pain stimuli in Wistar rats

This study investigates the impact of long-term nicotine exposure on pain hypersensitivity and cognitomotor functions after repeated pain stimuli in Wistar rats. The experimental design consisted of three phases of drug administration: short-term, 14 days; sub-chronic, 35 days; and long-term, 105 days, with treatment groups including nicotine (low: 0.1 mg/kg, high: 0.2 mg/kg), morphine (low: 5 mg/kg, high: 10 mg/kg), and their combination. Pain sensitivity was measured by the tail immersion, analgesy meter, and Randall-Selitto tests, while cognitive and motor functions were measured by the Navigational Maze and Rotarod tests, respectively. Results showed that morphine diminished pain hypersensitivity in a dose-dependent manner but that tolerance developed over time. Nicotine displayed dose-dependent analgesic properties, with higher doses significantly improving pain thresholds and enhancing cognitive performance, especially under conditions of chronic pain. Treatment of combined nicotine and morphine in a synergistic way resulted in better pain relief, improvement of cognitive, and motor functions than with each medicine separately taken. Low-dose nicotine was less effective not only in pain but also in cognitomotor assessment. These findings point to the potency of nicotine, especially in high doses, both as a cognitive enhancer and as an adjuvant to opioids for pain management. The study therefore suggests that a tailored, multi-drug therapeutic approach is in order if the shortcomings of classical analgesics are to be overcome and pain-induced cognitive and motor impairment reduced. Future studies will need to further determine the clinical applicability of these results while taking into account the risks of nicotine addiction.