Laurie's Blogs.

I have a lot of books on my book shelves, and I got looking at them the other day and thought, I should just open one up, flip through, and come up with a blog topic.  So I opened, Wall and Melzack’s Textbook of Pain.  A two inch thick book that looks impressive (but rarely cracks open).  When I flipped through, I landed on this topic… which was a good one, because the chapter had subsections that were animal-model specific.  So, join me on this learning journey!

It would appear that sex matters when it comes to experiencing pain.   In rodents, circulating levels of estrogens fluctuate in females during the estrous cycle and range from two to three times the level in males, whereas testosterone levels are four to five times greater in males.  Somatic and visceral nociceptive processing has been reported to fluctuate in parallel with the estrous cycle, thus strongly suggesting hormonal modulation, but nociceptive sensitivity to circulating levels of estrogens, and progesterone vary with the tissue and test.

Estrogen  seems to have a pro-nociceptive effect in regard to inflammatory stimuli or nerve injuries.  However, estrogen can suppress hyperalgesic priming (prolonged hyperalgesia to a noxious stimulus following a conditioning inflammatory stimulus).  This is demonstrated when intact rats are supplemented with estrogens or estrogens plus progesterone (to induce pseudopregnancy rates), whereby there is a predominantly analgesic effect.

Testosterone appears to have a pain-protective effect in male rats.  The anti-nociceptive response demonstrated in male rats is reduced following gonadectomy.

Ovariectomy decreased pain behaviour which is thought to reflect an increase in antinociceptive mechanisms.

The mechanisms underlying gonadal hormone modulation of nociception occur at many levels of the nervous system (peripherally and  at the spinal cord level).  Female neural afferent fibres have been shown to be more sensitive to subcutaneous or intramuscular glutamate than those of males (thus demonstrating an estradiol-dependent effect).   Estradiol also directly increases the excitability of dorsal root ganglion (DRG) neurons in vitro and increases somatic neural afferents (which is heightened even more in the presence of inflammation).  

Male rats also seems to enjoy the benefit of greater antinociception / analgesia due to opioid agonists as compared to female rats.  In short, testosterone seems to activate the opioid pathways whereas estrogen appears to decrease the effects.   Findings indicate that males express more u-opioid receptor proteins in the spinal cord and midbrain, especially when compared with females in proestrus.

What do we do with this information?

Honestly, I think this is just interesting to know.  Perhaps it impacts a female dog’s pain responses when they are in season.  Perhaps this give credence to the rationale of spaying a female sporting dog but to leave a male sporting dog intact.  

What else do you think we can make of this information?  It’s just interesting!

So, for now I’ll stick this book back on the shelf for another few years to pass by and move onto a different subject.

Until next time, Cheers!

Laurie

Reference:

Greenspan JD and Traub RJ. Gender Differences in Pain and Its Relief.  In Wall and Melzack’s Textbook of Pain, 6th Edition.  McMahon, Koltzenburg, Tracey, & Turk (eds).  Elsevier Saunders. Philadelphia, PA. 2013: