Glia cells and astrocytes are more and more widely recognized as important new targets, even to treat break through pain. ^{[28] [29][30][31]}

On each neuron in the CNS many more glia cells can be found. And also a single astrocyte enwraps 4 to 6 neuronal somata and contacts 300 to 600 neuronal dendrites ^[32] Thus glia cells and neurons are intensively intermingled. Activated astrocytes are mainly referred to glial fibrillary acidic protein (GFAP) upregulation and astrogliosis (hypertrophy of astrocytes).

Astrocyte activation as been found in many pain states such as in chronic constriction injury,^[33] after spinal nerve ligation,^[34][35] and due to tissue injury and/or inflammation.^[36][37]

Pharmacological attenuation of glial activation therfore represents a novel approach for controlling neuropathic pain. It has also been found that old molecules, such as propentofylline, pentoxifylline, fluorocitrate and minocycline decrease microglial activation and inhibit proinflammatory cytokines, thereby suppressing the development of neuropathic pain. ^[38] 

Although many networks within gliopathic pain exist, we give an example of two factors, Il-18 and the gap junction. 

Example: Il-18 

Astroglial reaction after nerve injury is more persistent than microglial reaction.^[39] Microglial reaction is ussually prior to astrocyte reaction. Interestingly, after nerve injury, the cytokine and its receptor Il-18 is upregulated on astrocytes and microglia.^[40] By blocking Il-18 the allodynia due to the nerve injury diminishes.

Gap Junctions 

Glia cells are interconnected with gap junctions (tubes in which ions flow from one cell to the other.^[41] When a nerve injury occurs, one component of gap junctions (connexin Cx43) is increasingly expressed.^[42] Inhibition of gap junction function by carbenoxolone produces analgesia in pain models.^[43]

Jan M. Keppel Hesselink, MD, PhD, and David J. Kopsky, October 2010, rev okt 2011, JMKH

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