Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain

Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14-18 days after spinal nerve ligation or sham surgery, and the effects of the FAAHinhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined. Intraplantar URB597 (25 _g in 50 _l) significantly ( p _ 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1 ) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (30_g in50_l) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of shamoperated rats. Intraplantar URB597 (25 _g in 50 _l) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 _g in 50 _l) significantly ( p_0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in shamoperated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats.

Narratives great and small: neighbourhood change, place and identity in Notting Hill

The area of Notting Hill in west London has been subject to much media coverage in recent years, which, along with substantial gentrification, has given rise to an image of the area as the epitome of fashionable London. This study investigates the views of those marginal to gentrification and mediated representation on their feelings about the local area, its image and their changing neighbourhoods. Many participants in the research resented some of the more recent changes in Notting Hill and the area's representation in the media. However, in contrast to expectations, most of the more working-class respondents involved in the research did not articulate much emotional attachment to the area. They were more concerned with what might be termed the material aspects of life in Notting Hill: convenience, facilities, safety and so on. In contrast, the more middle-class respondents frequently spoke of their regret of the changes to the area, such as the loss of independent shops, and the reduction in diversity. Paradoxically, the loss of working-class landscapes seems a relatively middle-class worry. The symbolically important landscapes described by working-class respondents were related to more immediate, material issues, in which gentrification was only a relatively minor concern. The definitive version is available at www.blackwell-synergy.com