Abstract
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. 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. 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. 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.
Highlights
Chronic pain is one of the most debilitating health problems worldwide as it negatively affects daily activities, reduces personal and social productivity, and generates hopelessness
The results showed that allodynia, which is a prominent Neuropathic pain (NP) symptom, was detected in all neuropathic mice, but tramadol (50 mg/kg, i.p.) stopped these symptoms
The results showed that NP decreased oocyte maturation and copulation rates of mice, and tramadol reversed all these effects
Summary
Chronic pain is one of the most debilitating health problems worldwide as it negatively affects daily activities, reduces personal and social productivity, and generates hopelessness. Similar to other types of chronic pain, NP is an inescapable stressor that significantly affects the quality of life according to the changes in the physical and mental functioning of patients. NP and chronic pain lead to permanent changes in brain structure and function, which can affect brain processes not directly connected with the pain itself [2]. The endocrine system is affected by NP [3] as NP activates the hypothalamic-pituitary-adrenal-thyroid-gonadal system, which controls the stress mechanism [4]. The relationships between chronic pain (and NP) and stress have been discussed in several recent reviews that have investigated the relevance of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadotropic (HPG), and corticotrophin-releasing hormone (CRH) axes [5, 6]. As a consequence of the interactions among these axes, chronic pain can affect reproductive function. One study on the effects of stress on fertility in dairy cows has been published [7], we found no experimental study that has analyzed the effects of NP on fertility
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