Nurses have been functioning in expanded roles as nurse practitioners (NPs) since 1965. The role has been characterized by controversy regarding economics, scope of practice, level of independence, accountability, and training since its inception. This article examines the response of the medical community to NPs during the first 15 years of their development. The medical literature from 1967 through 1982 was examined through a Medline search to ascertain the issues, attitudes, and barriers to practice that evolved as a foundation for understanding the present response of medicine to NPs.

History, 20th Century↗

PubMed1999

A diminution of delta9-tetrahydrocannabinol modulation of dynorphin A-(1-17) in conjunction with tolerance development.

Previous research in this laboratory concerning delta9-tetrahydrocannabinol-induced spinal antinociception indicated the critical role of dynorphin A-(1-17) in spinal antinociception following acute intrathecal (i.t.) administration. In the present study, tolerance development to delta9-tetrahydrocannabinol-induced spinal antinociception attenuated delta9-tetrahydrocannabinol-induced modulation of immunoreactive dynorphin A-(1-17). These data indicate that at lower doses of drug, desensitization of the cannabinoid receptor inhibits stimulation of downstream dynorphinergic neurons. However, at higher doses of drug, desensitization is overcome and spinal dynorphin A concentrations are increased by delta9-tetrahydrocannabinol. Antinociception in the absence of elevated dynorphin A-(1-17) levels in the tolerant rat suggests that factors other than the attenuated dynorphin release are components of antinociception in the tolerant state. The shift from the critical role of dynorphin A in cannabinoid antinociception vs. that in the non-tolerant state may indicate tolerance also at the kappa-opioid receptor, a role as yet undetermined.

Analgesics↗

PubMed1999

Cannabinoid modulation of dynorphin A: correlation to cannabinoid-induced antinociception.

Intrathecal administration of anandamide, delta9-tetrahydrocannabinol (THC) and (-)-3-[2-hydroxy-4-(1,1-dimethyheptyl)ptyl)phenyl]-4-(3-hydr oxypropyl)-cicloexan-1-ol (CP55,940) induced spinal antinociception accompanied by differential kappa-opioid receptor involvement and dynorphin A peptide release. Antinociception using the tail-flick test was induced by the classical cannabinoid THC and was blocked totally by 17,17'-bis(cyclopropylmethyl)-6',6,7,7'-tetrahydro-4,5,4'5'-diepoxy++ +-6,6'-(imino)[7,7'-bimorphinan]-3,3',14,14'-tetrol (norbinaltorphimine) indicating a significant and critical kappa-opioid receptor component. The endogenous cannabinoid, anandamide and the non-classical bicyclic cannabinoid, CP55,940, induced non-nor-BNI-sensitive effects. The N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR141716A)-mediated attenuation of spinal antinociception imparted by the various cannabinoids indicates cannabinoid CB1 receptor involvement. THC-induced an enhancement of immunoreactive dynorphin A release which coincided with the onset, but not duration antinociception. The release of dynorphin A was also attenuated by SR141716A suggesting it is cannabinoid CB1 receptor-mediated. These data indicate a critical role for dynorphin A release in the initiation of the antinociceptive effects of the cannabinoids at the spinal level.

Analgesics↗

PubMed1999