We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is
not homogeneous, however, and comprises three categories: physiological, inflammatory,
and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an …

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 …

Pain after nerve damage is an expression of pathological operation of the nervous system 1,
2, one hallmark of which is tactile allodynia—pain hypersensitivity evoked by innocuous
stimuli. Effective therapy for this pain is lacking, and the underlying mechanisms are poorly …

Amyloid-β peptide is elevated in the brains of patients with Alzheimer disease and is
believed to be causative in the disease process. Amyloid-β reduces glutamatergic
transmission and inhibits synaptic plasticity, although the underlying mechanisms are …

N-methyl-d-aspartate receptors (NMDARs) mediate ischemic brain damage but also
mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we
transduced neurons with peptides that disrupted the interaction of NMDARs with the …

Neuropathic pain is a common and severely disabling state that affects millions of people
worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect
peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in …

In the central nervous system, synaptic strength is regulated partly by changes in the
function and number of postsynaptic glutamate receptors. The NMDA (N-methyl-D-
aspartate) subtype of glutamate receptor (NMDAR) is regulated in part by the opposing …

The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmission and plasticity in
the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In
membrane patches excised from mammalian central neurons, the endogenous tyrosine …

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 …

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for
neuronal development, but their functions in the adult CNS are unknown. We report that
ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95 …