Abstract
Neuropathic pain presents a huge societal and individual burden. The limited efficacy of current analgesics, diagnostic markers and clinical trial outcome measures arises from an incomplete understanding of the underlying mechanisms. A large and growing body of evidence has established the important role of microglia in the onset and possible maintenance of neuropathic pain, and these cells may represent an important target for future therapy. Microglial research has further revealed their important role in structural remodelling of the nervous system. In this review, we aim to explore the evidence for microglia in sculpting nervous system structure and function, as well as their important role in neuropathic pain, and finally integrate these studies to synthesize a new model for microglia in somatosensory circuit remodelling, composed of six key and inter-related mechanisms. Summarizing the mechanisms through which microglia modulate nervous system structure and function helps to frame a better understanding of neuropathic pain, and provide a clear roadmap for future research.
Highlights
Neuropathic pain is defined as ‘pain caused by a lesion or disease of the somatosensory nervous system’ [1]
It is likely that the spatial segregation of microglia allows different phenotypes in different regions to differentially modulate the pain signature network; harvesting microglia from biopsies of different brain regions in neuropathic pain models will elucidate the spatial distribution of the molecular signature of microglia at different time points and how this correlates with structural alterations and whole-brain connectivity [194]
The framework proposed suggests a pro-inflammatory microglial phenotype modulates the excitability of sensory neurons in the dorsal horn to mediate hyperalgesia
Summary
Neuropathic pain is defined as ‘pain caused by a lesion or disease of the somatosensory nervous system’ [1]. Less than 50% of current analgesics provide even 50% pain relief [7] and there are significant problems in drug interactions, convenience, adherence and little effect on physical and emotional functioning. This is probably due to reliance on redundant, nonspecific targets and assessment by traditional randomized controlled trials with inappropriate outcome measures that do not consider biopsychosocial factors (reviewed in [8,9]). We further explore the latest research into microglial mechanisms in driving neuropathic pain states [13,14,15,16], and critically analyse important insights relating structural changes of neuronal circuitry to the neuropathic phenotype (reviewed in [17,18]). We synthesize a new model for microglia in somatosensory circuit remodelling, composed of six key and inter-related mechanisms, that define the contributions of these mechanisms to the neuropathic pain state
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
