Glia and pain: Is chronic pain a gliopathy?
Dr Ji et al discussed chronic painful syndromes and their association with different glial activation states, and they sumerized 4 aspects related to glia behavior in chronic pain:
(1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks);
(2) phosphorylation of mitogen-activated protein kinase signaling pathways;
(3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and
(4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space.
They concluded their review:
Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of “gliopathy,” that is, dysregulation of glial functions in the central and peripheral nervous system.
As palmitoylethanolamide has been proven to be a glia modulator, as well as a mast cell modulator, it makes a lot of sense to start treating chronic pain via a new target, the overactive glia.
Source: Ji RR, Berta T, Nedergaard M. Glia and pain: Is chronic pain a gliopathy? Pain. 2013 Dec;154 Suppl 1. doi: 10.1016/j.pain.2013.06.022.