Neuropathic pain: the paradox of dynorphin.
One of the curious but common consequences of opioid administration in the clinical setting is the induction, at sites uninvolved in the original presentation of discomfort, of pain itself. The induction of pain is also a reliable, measurable phenomenon in animals receiving continuous delivery of opioid. Such pain induction is associated with the expression of spinal dynorphin, a finding that is especially intriguing in light of dynorphin's ability to recapitulate many of the characteristics of chronic, neuropathic pain when administered intrathecally (i.e., into the spine). The effective treatment of chronic pain syndromes-and of tolerance to antinociceptive therapies-may thus rest on an understanding of the biological roles of dynorphin in neurotransmission.
Lai
J
J
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Ossipov
M H
MH
Vanderah
T W
TW
Malan
T P
TP
Porreca
F
F
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D007278:Injections, Spinal; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D004399:Dynorphins