Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability
of neurons in the dorsal horn of the spinal cord 1, 2, 3. Spinal microglia stimulated by ATP
contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury …

Microglia in the dorsal horn of the spinal cord are increasingly recognized as being crucial in
the pathogenesis of pain hypersensitivity after injury to a peripheral nerve. It is known that
P2X4 purinoceptors (P2X4Rs) cause the release of brain-derived neurotrophic factor …

Invasive procedures that would be painful in children and adults are frequently performed on
infants admitted to the neonatal intensive care unit. This article discusses sensory responses
to these procedures in the immature nervous system and highlights the fact that, in addition …

A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling
is essential for chronic pain hypersensitivity. Using multiple approaches, we found that
microglia are not required for mechanical pain hypersensitivity in female mice; female mice …

Microglia were described by Pio del Rio-Hortega (1932) as being the 'third element'distinct
from neurons and astrocytes. Decades after this observation, the function and even the very
existence of microglia as a distinct cell type were topics of intense debate and conjecture …

Recent findings challenge the concept that microglia solely function in disease states in the
central nervous system (CNS). Rather than simply reacting to CNS injury, infection, or
pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS …

Chronic pain is highly variable between individuals, as is the response to analgesics.
Although much of the variability in chronic pain and analgesic response is heritable, an
understanding of the genetic determinants underlying this variability is rudimentary 1. Here …

A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the
gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing
treatment with morphine resulted in downregulation of the K+-Cl− co-transporter KCC2 …

Disinhibition of neurons in the superficial spinal dorsal horn, via microglia–neuron signaling
leading to disruption of chloride homeostasis, is a potential cellular substrate for neuropathic
pain. But, a central unresolved question is whether this disinhibition can transform the …

The innate immune system is increasingly appreciated to play an important role in the
mediation of chronic pain, and one molecule implicated in this process is the Toll-like
receptor 4 (TLR4). Here, using pharmacological and genetic manipulations, we found that …