Technologies

Endogenous opioid peptides and receptors evolved to modulate nociceptive input in response to injury. One of those peptides, dynorphin, acts on the kappa opioid receptor subtype to produce analgesia without sedation, respiratory depression or constipation. Prior to this invention, dynorphin was not an acceptable analgesic because of certain severe toxic side effects, when given in doses higher than physiological concentrations, mainly NMDA mediated neurotoxicity. Dynorphin produces its deleterious side effects by producing an NMDA mediated motor paralysis. In disease states such as stroke, spinal cord injury or neuropathic pain, activation of NMDA receptors by endogenous dynorphin may lead to neurodegeneration, hyperalgesia and allodynia. Tolerance to opiate drugs may also be mediated by the NMDA actions of dynorphin. This invention provides materials and methods to block NMDA receptor activation by dynorphin thus allowing the use of exogenous dynorphin as a beneficial nociceptive agent without side effects and preventing pathological actions of endogenous dynorphin in response to injury.