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Sex Differences in Pain

Klara Hatinova



Year of study:


Peripheral neuropathic pain (NP) arises from a lesion or damage to a peripheral nerve and increases pain signals transmission. NP is maladaptive (the pain perceived does not protect the damaged area), and conventional analgesic medication often does not reduce NP. The prevalence of NP in the clinical population is 4% in men, but 8% in women. Despite women representing most of the clinical population, pre-clinical animal research has focused mainly on male models. Since introducing Sex as a Biological Variable in 2016, more works have started including female animals in their research and discovered that the underlying mechanism of female NP is distinct to that observed in males.
Activation of microglia, innate immune cells in the central nervous system, has been essential for NP in males. However, in females, their suppression did not relieve NP symptoms and T-cells were identified as necessary for female NP. The results of my literature search confirm activation of microglia was not necessary for female NP, supported by differences in multiple neurone-microglia signalling pathways. Differences in gene expression endorsed the role of T-cells in females and a pro-inflammatory tendency in male microglia. These differences in immune cells were found to be regulated by sex hormones. Surprisingly, cellular changes in the spinal cord responsible for increased pain signalling were common to both sexes. Closer investigation of the role of T-cells in NP can increase the efficiency of medication and demonstrates the importance of investigating both sexes in preclinical research.

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