Central Glia as Prospective Targets in Chronic Pain

The pharmacology against chronic, especially neuropathic, pain is largely unsatisfactory despite its high prevalence in the population, extremely debilitating nature and associated socioeconomic burden. Molecules in the current medicinal arsenal are mostly designed to symptomatologically target peripheral actors of tissue injury or components of neuronal hyperexcitability. These medicines particularly include opiates, sodium channel blockers, modulators of excitatory or inhibitory neurotransmission and anti-inflammatory drugs. However chronic pain is not merely a peripheral or neuronal condition. Indeed, a revolutionary vision has emerged over the past decade positing that amid the profound central plasticity associated with chronic pain, molecular changes occurring in glia are pivotal. A surge of interest has therefore spread in the field ultimately leading to a flourishing wealth of data with respect to the involvement of astrocytes and microglia in pathological pain in experimental models. Nevertheless, the vital roles exerted by glial cells argue in favour of the development of well-designed regulators of glial physiology rather than full inhibitors of glial physiology. In addition, despite the extent of data released regarding glial modifications in animal models, only scarce evidence point to a similar plasticity in human. The current chapter aims to expose the promising recent developments in the quest of modulators of glial activity, particularly emphasizing the hurdles embodied by their pharmacodynamics and pharmacokinetics specificities. The credibility and bench-to-hospital potential of the few disclosed emerging glia-active compounds that are currently in the pipeline are critically discussed. A foremost attention is given to the specific case of neuropathic pain owing to the important literature available in the field, but the discussion spreads to wider perspective that includes other forms of chronic pain.

Keywords: Chronic pain, neuropathic pain, glia, astrocytes, microglia, pharmacology, MAP Kinases, antibiotics, transporters, animal models, clinical trials.