Changes in the expression of TRP channels induced by oxaliplatin in lumbar dorsal root ganglia and spinal cord of male and female rats

MIGUEL, CONSTANZA A.; M.V NOYA-RIOBÓ; M.A ZAPATA VACA; FB SBERNA GALLETO; L.A FAL; M.J. VILLAR; M.F CORONEL

Congreso; Peripheral Nerve Society annual meeting 2022; 2022

Transient receptor potential (TRP), cation channels involved in the detection of different types of stimuli, play a crucial role in pain neurotransmission. TRPA1 can be activated by chemical, thermal (cold) and mechanical stimuli; TRPV1 by capsaicin, noxious heat and low pH; TRPM8 by cool temperatures and cooling compounds. Interestingly, TRP expression and activity have been proposed to be regulated by sex hormones. In addition, sex differences have been observed in the expression of clinical and experimental pain. However, they have not yet been evaluated in oxaliplatin-induced pain. The objective of our work was to evaluate the development of mechanical and cold allodynia in animals exposed to oxaliplatin, analyzing the existence of sex-related differences. We also analyzed the expression of TRPV1, TRPM8 and TRPA1 in lumbar dorsal root ganglia (DRGs) and spinal cord (SC) of control and oxaliplatin-treated animals. Adult male and female rats were injected with oxaliplatin or saline. Mechanical and cold allodynia were assessed using von Frey and Choi tests, and TRPs mRNA levels were evaluated by real time RT-PCR. Oxaliplatin administration induced the development of mechanical and cold hypersensitivity and allodynia in both male and female animals. No significant sex-related differences were observed. Oxaliplatin also induced a significant increase in the expression of TRPV1, TRPM8 and TRPA1 in the DRGs of male and female rats. Interestingly, while TRPV1 and TRPA1 upregulation showed no sex difference, the increase in TRPM8 mRNA levels was more pronounced in female ganglia. TRPV1 and TRPM8 were also found to be upregulated in the SC of both male and female rats.Our results show that the upregulation of TRPV1, TRPM8 and TRPA1 may contribute to oxaliplatin-induced mechanical and cold allodynia in males and females.