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"Different immune cells mediate mechanical pain hypersensitivity in male and female mice"(microglia)

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
Messages
721
Location
Canada
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4053.html



from a NYT article about the findings:
http://www.nytimes.com/2015/07/19/opinion/sunday/why-science-needs-female-mice.html?_r=1
...
A new study published in the journal Nature Neuroscience suggests that research done on male animals may not hold up for women. Its authors reported that hypersensitivity to pain works differently in male and female mice. For males, immune cells called microglia appear to be required for pain hypersensitivity, and inhibiting their function also relieves the pain. But in female mice, different cells are involved, and targeting the microglia has no effect. If these differences occur in mice, they may occur in humans too. This means a pain drug targeting microglia might appear to work in male mice, but wouldn’t work on women.
...

Abstract from the study:
Different immune cells mediate mechanical pain hypersensitivity in male and female mice
A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, we found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research.
 
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voner

Senior Member
Messages
592
pretty amazing research. if anybody's interested in pain or microglia research – I highly recommend this read. I read this short neuroscience communication paper and the press releases surrounding it. they don't present much detail, but it appears to be a valid and robust study.

most pain research is done on mice – male mice only ( The females more complex hormonal system makes it more difficult to tease out the data implications). this research potentially invalidates or puts into question a lot of the pain research, especially when to comes to females.

this paper also clearly demonstrates the complexities and the involvement of the immune system and the nervous system and also the additional complexities that are involved in female system ( at least in my eyes).. Females seem to use different pathways for allodynia pain transmission than mice, but also can use The male pathway that uses microglia if the adaptive immune system pathway is blocked.

among their many findings, they state,

These data indicate that, in the absence of adaptive immune cells, female mice use the male, glial-dependent pathway, as was the case for testosterone-treated females.

and another:

The behavioral sex difference was accompanied by an analogous sex difference in dorsal horn gene expression, whereby SNI upregulated P2rx4 gene expression in male, but not female, mice (Supplementary Fig. 7).


SNI is spared nerve injury. P2x4 is one of the upregulated genes in people with "cfs with FM" in the study by Dr. Alan Light.....and that study looked at female and male subjects...human...

As @Jonathan Edwards has pointed out repeatedly, This research also shows the importance of good research study design; in this case the consideration of potential sex differences.

and of course, it's always good to keep in mind that it's a long ways from mice to humans....
 
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Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
This research also shows the importance of good research study design; in this case the consideration of potential sex differences.
The pharmaceutical industry are well aware of this problem. The trouble with female research subjects is that they have a tendency to become pregnant, even when not planning to be so.

Klimas and Broderick are studying sex differences in the immune systems of male and female patients with ME/CFS and GWI