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 inhibit...
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2006
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| Online Access: | https://eprints.nottingham.ac.uk/449/ |
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| author | Jhaveri, Maulik Richardson, Denise Kendall, David Barrett, David Chapman, Victoria |
| author_facet | Jhaveri, Maulik Richardson, Denise Kendall, David Barrett, David Chapman, Victoria |
| author_sort | Jhaveri, Maulik |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
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| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T18:12:13Z |
| publishDate | 2006 |
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| spelling | nottingham-4492020-05-04T20:29:20Z https://eprints.nottingham.ac.uk/449/ Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain Jhaveri, Maulik Richardson, Denise Kendall, David Barrett, David Chapman, Victoria 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. 2006-12 Article PeerReviewed Jhaveri, Maulik, Richardson, Denise, Kendall, David, Barrett, David and Chapman, Victoria (2006) Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain. The Journal of Neuroscience, 26 (51). pp. 13318-13327. Key words: electrophysiology; endocannabinoid; spinal nerve ligation; URB597; CB1 receptor; opioid receptor |
| spellingShingle | Key words: electrophysiology; endocannabinoid; spinal nerve ligation; URB597; CB1 receptor; opioid receptor Jhaveri, Maulik Richardson, Denise Kendall, David Barrett, David Chapman, Victoria Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title | Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title_full | Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title_fullStr | Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title_full_unstemmed | Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title_short | Analgesic Effects of Fatty Acid Amide Hydrolase Inhibition in a Rat Model of Neuropathic Pain |
| title_sort | analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain |
| topic | Key words: electrophysiology; endocannabinoid; spinal nerve ligation; URB597; CB1 receptor; opioid receptor |
| url | https://eprints.nottingham.ac.uk/449/ |