MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice.

This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. Cognitive performance was also significantly compromised in the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons of the PLC; excitatory responses increased, whereas inhibitory responses decreased after BLA stimulation. mGluR7 expression, mainly associated with vesicular glutamate transporter, increased in the hippocampus and decreased in the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and mechanical thresholds and open-arm choice. It reduced the immobility in the tail suspension test and the number of marbles buried and of digging events in the marble burying test. MMPIP also improved cognitive performance and restored the balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM, reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia, tail suspension, and marble burying test. Altogether, these findings show that mGluR7 NAMs reduce pain responses and affective/cognitive impairments in neuropathic pain conditions.

Datura stramonium intake: a report on three cases.

This article describes three cases of Datura stramonium intake on two nonconsecutive days. In the first case, the patient took a small amount of D. stramonium seeds without showing any symptoms of intoxication. The other two patients had taken a considerable amount of seeds and reported a sudden surge in strength and energy, with some aggressive compulsion towards their peers. They showed delirium as well as confusion and disorientation. The absence of any specific legislation makes D. stramonium a tempting alternative to other psychoactive substances. Thus, it is extremely important to be able to recognize its symptoms so as to be able to diagnose any signs of intoxication properly.

A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice.

The neuropathic pain model consisting of the spared nerve injury of the sciatic nerve was used in the mouse to examine whether peripheral neuropathy is capable of generating over-expression of pro-inflammatory and pro-apoptotic genes in the orbito-frontal cortex, together with allodynia and hyperalgesia. RT-PCR analysis showed increased expression of caspase-1, caspase-12 and caspase-8 genes in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve. Conversely, the expression of caspase-3 was decreased by spared nerve injury of the sciatic nerve in the same brain area. A single subcutaneous injection of ozone performed 12 h after the surgical procedure decreased mechanical allodynia and normalized the mRNA caspase-1, caspase-12 and caspase-8 gene levels, but did not the decrease caspase-3 level, 14 days post-spared nerve injury. Ozone also reduced IL-1beta staining in the orbito-frontal cortex in neuropathic mice. This study provides evidence that a single subcutaneous administration of ozone decreased neuropathic pain type behaviour, normalized the expression of pro-inflammatory caspases and reduced IL-1beta staining in the orbito-frontal cortex astrocytes in SNI mice. These preliminary data show that peripheral neuropathy induced over-expression of pro-inflammatory/pro-apoptotic caspases in the orbito-frontal cortex and that ozone, by mechanisms that are as yet unknown, can regulate the expression of the genes that play a pivotal role in the onset and maintenance of allodynia.