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Neurons in the rostroventromedial medulla (RVM) project to spinal loci where the neurons inhibit or facilitate pain transmission. Abnormal activity of facilitatory processes may thus represent a mechanism of chronic pain. This possibility and the phenotype of RVM cells that might underlie experimental neuropathic pain were investigated. Cells expressing(More)
The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are mostly ineffective. We recently demonstrated that antisense mediated "knock-down" of the sodium channel isoform, Na(V)1.8, reverses neuropathic pain behavior after L5/L6 spinal nerve ligation (SNL), implicating a critical functional role of Na(V)1.8 in the(More)
Differential expression of ion channels contributes functional diversity to sensory neuron signaling. We find nerve injury induced by the Chung model of neuropathic pain leads to striking reductions in voltage-gated K(+) (Kv) channel subunit expression in dorsal root ganglia (DRG) neurons, suggesting a potential molecular mechanism for hyperexcitability of(More)
Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of sodium channels at the site of injury. Here, we show that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral(More)
Alterations in sodium channel expression and function have been suggested as a key molecular event underlying the abnormal processing of pain after peripheral nerve or tissue injury. Although the relative contribution of individual sodium channel subtypes to this process is unclear, the biophysical properties of the tetrodotoxin-resistant current, mediated,(More)
Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking the prodynorphin gene were studied for sensitivity to non-noxious and noxious stimuli, before and after induction of experimental neuropathic pain. Prodynorphin knock-out (KO) mice had normal responses(More)
Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. Recent studies revealed that cholecystokinin (CCK) is(More)
Although injury-induced afferent discharge declines significantly over time, experimental neuropathic pain persists unchanged for long periods. These observations suggest that processes that initiate experimental neuropathic pain may differ from those that maintain such pain. Here, the role of descending facilitation arising from developing plasticity in(More)
Management of acute pain remains a significant clinical problem. In preclinical studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects. The CB2 receptor-selective agonist AM1241 produces antinociceptive effects that are antagonized by CB2, but not CB1, receptor-selective antagonists,(More)
Complete or partial spinal section at T(8) has been shown to block tactile allodynia but not thermal hyperalgesia following L(5)/L(6) spinal nerve ligation (SNL), suggesting the supraspinal integration of allodynia in neuropathic pain. In the present study, the possibility of mediation of nerve injury-associated pain through tonic activity of descending(More)