Glial modulation of pain: a step beyond.

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see Review of Wei et al. Neuropathic pain is an important public health problem because it is frequently debilitating, intense, unremitting, and resistant to available therapies. Peripheral neuropathies can result from any type of neural damage, including that triggered by physical trauma, infection, inflammation , metabolic abnormalities, vascular abnormalities, neurotoxins, chemothera-peutic agents, radiation or autoimmune disease. Many changes in neuronal function across the nociceptive system are associated with the genesis of neuropathic pain, including ectopic discharge, exaggerated release of neurotransmitters, and long-term potentiation. Nevertheless, much evidence has suggested that this plasticity does not occur autonomously in neurons, but also depends on glial cells. The role of interactions between glia and neurons in the induction of neuro-pathic pain has gained much attention in the last decade. At least in experimental models of peripheral neuropathies, abnormal neuronal inputs from the site of injury to the CNS strongly activate micro-glia and astrocytes, mainly in the spinal cord and trigeminal nucleus. Subsequently , these cells release many substances that directly or indirectly act upon neurons in the nociceptive system, amplifying pain (Watkins and Maier, 2002). In addition to processes in the spinal cord and trigeminal nucleus, the induction and maintenance of neuropathic pain also seems to depend on supraspinal areas of the CNS, such as rostral ventro-medial medulla (RVM). A well established hypothesis posits that nociceptive information from damaged nerves project directly or indirectly to the RVM, activating a subset of descending serotonergic neurons that project to the spinal cord or trigeminal nucleus. These descending inputs activate 5-HT3 receptors and thereby enhance pain transmission (Vanegas and Schaible, 2004). In a recent study published in The Journal of Neuroscience, Wei et al. (2008) further explored the contribution of neuron– glia interactions in the genesis of neuropathic pain by investigating whether this cross talk occurs in areas of the CNS beyond the spinal cord and tri-geminal nucleus. Using a model of peripheral lesion of the infraorbital nerve, which produces severe and long-lasting pain-related behaviors [Wei et al. authors observed an increase in the expression of specific markers of astrocyte (GFAP and S110␤) and microglia (CD11 and Iba1) …