Immune drivers of physiological and pathological pain, 2024, Aakanksha Jain et al

Physiological pain serves as a warning of exposure to danger and prompts us to withdraw from noxious stimuli to prevent tissue damage. Pain can also alert us of an infection or organ dysfunction and aids in locating such malfunction. However, there are instances where pain is purely pathological, such as unresolved pain following an inflammation or injury to the nervous system, and this can be debilitating and persistent.

We now appreciate that immune cells are integral to both physiological and pathological pain, and that pain, in consequence, is not strictly a neuronal phenomenon.

Here, we discuss recent findings on how immune cells in the skin, nerve, dorsal root ganglia, and spinal cord interact with somatosensory neurons to mediate pain. We also discuss how both innate and adaptive immune cells, by releasing various ligands and mediators, contribute to the initiation, modulation, persistence, or resolution of various modalities of pain.

Finally, we propose that the neuroimmune axis is an attractive target for pain treatment, but the challenges in objectively quantifying pain preclinically, variable sex differences in pain presentation, as well as adverse outcomes associated with immune system modulation, all need to be considered in the development of immunotherapies against pain.

https://rupress.org/jem/article-sta...une-drivers-of-physiological-and-pathological

 

A recent article in Science Daily was about a finding that proteasomes are involved with nerve communication in sensory cells in the skin. For every simplistic model of body functions, there are probably still plenty of undiscovered subsystems involved.

 

A warning is a sign of an impending problem. Pain does not occur as a warning of possible harm, it occurs as a signal of harm. Now it could be oddly framed as a warning to prevent more damage, but at the micro level obviously it is occurring not as a warning system, but as something that is happening. This framing is so odd, I don't get it. It's so ingrained in medical culture that pain is just a signal of something that could happen, rather than something that is happening right here and now. This framing has done and continues to cause so much harm.