Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain.
In the central nervous system, bidirectional signaling between glial cells and neurons ('neuroimmune communication') facilitates the development of persistent pain. Spinal glia can contribute to heightened pain states by a prolonged release of neurokine signals that sensitize adjacent centrally projecting neurons. Although many persistent pain conditions are disproportionately common in females, whether specific neuroimmune mechanisms lead to this increased susceptibility remains unclear. This review summarizes the major known contributions of glia and neuroimmune interactions in pain, which has been determined principally in male rodents and in the context of somatic pain conditions. It is then postulated that studying neuroimmune interactions involved in pain attributed to visceral diseases common to females may offer a more suitable avenue for investigating unique mechanisms involved in female pain. Further, we discuss the potential for primed spinal glia and subsequent neurogenic inflammation as a contributing factor in the development of peripheral inflammation, therefore, representing a predisposing factor for females in developing a high percentage of such persistent pain conditions.
Discipline of Physiology, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
K N
KN
Dodds
Discipline of Physiology, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
E A H
EA
Beckett
Discipline of Pharmacology, School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Pelvic Pain SA, Norwood, SA, Australia.
S F
SF
Evans
Discipline of Pharmacology, School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
P M
PM
Grace
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
L R
LR
Watkins
Discipline of Physiology, School of Medicine, University of Adelaide, Adelaide, SA, Australia.|ARC Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, SA, Australia.
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MR
Hutchinson
D000818:Animals; D059350:Chronic Pain / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D020078:Neurogenic Inflammation / Q000276:immunology / Q000503:physiopathology*; D009457:Neuroglia / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000276:immunology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D012737:Sex Factors; D013116:Spinal Cord / Q000276:immunology / Q000503:physiopathology*; D059265:Visceral Pain / Q000276:immunology / Q000503:physiopathology*