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.
