Adolescent nicotine exposure increases nociceptive behaviors in rat model of formalin test: Involvement of ventrolateral periaqueductal gray neurons

Among the major life-threatening factors, smoking tobacco is the leading cause of death worldwide. Adolescence is a sensitive stage of brain development, and smoking at this age is thought to be associated with neural and behavioral alterations. Currently the association between adolescent tobacco use and pain perception remained to be addressed. It is also important to consider that the periaqueductal gray (PAG) is a major component of the descending pain inhibitory system. The present study was performed to reveal the possible effects of adolescent nicotine consumption on pain-related behaviors and also the antinociceptive effect of a single dose of morphine administration besides the ventrolateral PAG (vlPAG) firing assessment in adulthood during formalin test. Adolescent male Wistar rats were administered with either a nicotine or saline injection (s.c.), and after 30 days of washout period, formalin test was performed. The vlPAG neuronal responses to formalin injection were recorded via in vivo extracellular single-unit recording. The results demonstrated that adolescent nicotine exposure enhances behavioral responses to pain. It also reduced morphine-induced antinociceptive behavior in the formalin test during adulthood. Moreover, adolescent nicotine exposure attenuates the extent of vlPAG inhibitory response to formalin. Our data provided a further conclusion that adolescent nicotine exposure may alter the pain modulatory systems and their subsequent response to painful stimuli.