Tramadol Reverses the Effects of Neuropathic Pain on Oocyte Maturation and Copulation Ratio in Mice

Objective: Neuropathic pain (NP) is an inescapable stressor that significantly affects both the nervous and endocrine system functions. In this study, we investigated the effect of NP on female reproductive function using the number of oocytes as an index as well as the copulation rates of female mice, with and without males. We also examined whether NP symptoms stopped after injecting tramadol, an opioid analgesic. Materials and Methods: The partial sciatic nerve was tightly ligated to produce neuropathy, and allodynia was assessed using the cold-plate test. A superovulation protocol was applied to control, sham, neuropathy, and neuropathy+tramadol groups. Each group was divided into two subgroups according to two housing conditions: female alone and female with a male. After inducing superovulation, oocytes/zygotes were isolated from the ampulla of female mice. Total number of oocytes, oocyte maturation, and copulation rates were determined. Results: The results showed that allodynia, which is a prominent NP symptom, was detected in all neuropathic mice, but tramadol (50 mg/kg, i.p.) stopped these symptoms. The results also showed that NP decreased oocyte maturation and copulation rates of mice, and tramadol reversed all these effects. Conclusion: In conclusion, we suggest that NP affects reproductive performance by altering the regulation of neuroendocrine mechanisms. Prospective studies that determine the levels of cortisol, fertility hormone, cytokine, and other potential endogenous substances in NP animals are needed to clarify the mechanisms.