PubMed · 14341120
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C H HODGE. 1965. OXYCODONE IN LABOUR.. https://doi.org/10.1111/j.1471-0528.1965.tb00075.x
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The aims of the present study were to investigate, in rats, the behavioral effects of substance P (SP) microinjected into the ventrolateral periaqueductal gray (PAG) and the effects of the neurokinin 1 (NK-1) receptor antagonist [d-Arg1, d-Trp7, 9, Leu11]-substance P (Spantide). The effect of morphine administration on the release of SP in the ventrolateral PAG was also investigated using microdialysis in awake rats. SP microinjected into the ventrolateral part of the PAG induced significant increases in the hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation as an antinociceptive response. The NK-1 receptor antagonist blocked these effects but exhibited no antinociceptive effect alone. Subcutaneous administration of morphine increased basal SP-like immunoreactivity (SP-LI) release in the microdialysate obtained from the ventrolateral PAG of freely moving rats. Our results demonstrate that SP injected into the ventrolateral PAG induces an antinociceptive effect via activation of NK-1 receptors. Morphine administered systemically induces the release of SP in the ventrolateral PAG. We suggest that an increased release of SP in the PAG may contribute to opioid antinociception.
We characterized the effect of a novel selective histamine H1 receptor antagonist, (R)-1-(3-(10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid (ReN-1869), on the responses of dorsal horn neurons in anesthetized rats after carrageenan induced-inflammation and peripheral neuropathy (L5/6 spinal nerve ligation; SNL). ReN-1869 was administered systemically (0.1-4 mg/kg), and drug effects were assessed using a wide range of peripheral electrical and natural stimuli (brush, von Frey filaments, and heat). Comparisons were made between unoperated naive groups and either carrageenan inflamed or SNL rats. ReN-1869 produced little effect on the electrically evoked responses (wind-up, Abeta-, Adelta-, and C-fiber-evoked responses); however, it significantly attenuated neuronal responses to noxious heat in carrageenan and SNL rats. A robust effect was seen with the low-threshold mechanical punctate (von Frey 9 g) stimuli, which were selectively inhibited by ReN-1869 after tissue and nerve injury. These inhibitory actions were in marked contrast to the naive animal group, where only nonsignificant effects were observed. To investigate whether the actions of ReN-1869 are mediated via the antagonism of histamine H1 receptors, the effects of this novel compound were compared with that of another H1 receptor antagonist, mepyramine (1-20 mg/kg). Systemic mepyramine produced strong inhibitions of the 9-g von Frey-evoked responses in carrageenan and SNL rats. The similar pharmacological profile of these two compounds suggests for a similar mechanism of action. We propose that ReN-1869 may represent a novel agent for the treatment of certain modalities of persistent pain states, in particular for the treatment of mechanical allodynia.
The present study was carried out to investigate the effects of neuropeptide Y (NPY) in the midbrain periaqueductal grey (PAG) on the nociceptive modulation in mononeuropathic rats. NPY was microinjected into the PAG. The latency of paw withdrawal (PWL), assessed by the hot-plate (52 ) and the Randall Selitto test, was measured. Intra-PAG administration of 0.05, 0.1 and 0.2 nmol of NPY significantly increased the PWLs in a dose-dependent manner. Co-administration of 0.2 nmol of NPY(28-36) and 5.5 nmol of naloxone significantly attenuated the NPY-induced increase in PWLs. The results suggest that Y(1) receptor may mediate NPY-induced anti-nociception, and that the opioid receptors in PAG may also be involved in this process in mononeuropathic rats.