Recently, a study led by University of Arizona Health Sciences researchers published in the journal Brain, demonstrated for the first time functional sexual dimorphism in nociceptors.

• Activation of nociceptors likely produces the same perception of pain in men and women. What is different is how the nociceptors are activated.

About Nociceptor Cells

Nociceptors are the nerve cells responsible for perceiving pain.

• Existence: Nociceptor cells have bare nerve endings and they are found across skin, bones, joints, and muscles. 
• Detection: The receptors detect extreme pressure, temperature, and chemical signals released by the body when it is injured, turn them into electrical signals, and relay them to the brain via the spinal cord. The brain finally reads the message and perceives pain.
• Activation Process: While the nociceptors are normally activated by high-intensity stimuli, under some circumstances the threshold for their activation may be decreased allowing low intensity and normally physiological stimuli to activate them and produce pain.

Crucial Insights on the Findings of the New Study

• Activation Threshold: In the new study, the researchers studied how prolactin and orexin-B affect on nociceptor activation thresholds in the nerve cell samples they had. 
  • In the mice cohort, a technique to separate and identify proteins revealed prolactin had increased the firing-up of nociceptors in females and orexin-B had done the same thing in the males. 
  • Immunohistochemistry analysis of monkeys and humans also revealed similar effects.
• Differentially Sensitized: Nociceptors from male and female animals or humans can be differentially ‘sensitised’, i.e. have a lowering of their activation threshold.
• On Therapies: Unravelling the different mechanisms that drive nociceptor sensitisation and activation will bring us a step closer to understanding qualitative sex differences in pain perception, which in turn is essential to design precise and sex-specific pain therapies.
• Presentation of A Unique Concept: The study presents a unique concept that nociceptors are either male or female.

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Implications of the Study

The researchers expect their findings have two implications for medical research.

• Sex-Specific Therapy: It will encourage medical practitioners to factor in the sex of a patient when making decisions about pain therapies.
• Consider the Number of Trial Members: In clinical trials of therapies with new pain treatment mechanisms, researchers will have to be more careful about the number of men and women in the trial so that they might be alerted to effects that may only occur in one sex.
• Revisit Failed Clinical Trials: It might be time to revisit some ‘failed’ clinical trials to check if there might have been a sex-specific effect to a drug.

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