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 …

Modern pain-control theory 1 predicts that a loss of inhibition (disinhibition) in the dorsal
horn of the spinal cord is a crucial substrate for chronic pain syndromes 2. However, the
nature of the mechanisms that underlie such disinhibition has remained controversial 3, 4, 5 …

Neuropathic pain resulting from damage to or dysfunction of peripheral nerves is not well
understood and difficult to treat. Although CNS hyperexcitability is a critical component,
recent findings challenge the neuron-centric view of neuropathic pain etiology and …

Peripheral nerve injury can induce spinal microglial/astrocyte activation. Substances
released by activated glial cells excite spinal nociceptive neurons. Pharmacological
disruption of glial activation or antagonism of substances released by activated glia prevent …

The original proposal that substance P is involved in the regulation of nociceptive
information at the first sensory synapse in the spinal cord has been substantiated by a wide
range of evidence, but definitive support has been lacking, due primarily to the lack of …

The development of new therapeutic approaches to the treatment of painful neuropathies
requires a better understanding of the mechanisms that underlie the development of these
chronic pain syndromes. It is now well established that astrocytic and microglial cells …

Tight‐seal, whole‐cell voltage clamp recording techniques were used to characterize
monosynaptically evoked GABAB currents in adult rat brain slices maintained at 34‐35
degrees C. Responses were recorded from granule cells of the dentate gyrus following the …

Adjusting input–output gain is crucial for information processing by the brain. Gain control of
subthreshold depolarization is commonly ascribed to increased membrane conductance
caused by shunting inhibition. But contrary to its divisive effect on depolarization, shunting …

Whole-cell patch-clamp recordings unveiled a substantial increase in the amplitude, but no
change in the frequency, of miniature inhibitory postsynaptic currents (mIPSCs) in dentate
gyrus granule cells following chronic epilepsy induced by kindling. This novel and persistent …

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 …