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The Journal of Neuroscience, March 25, 2009, 29(12):3766-3780; doi:10.1523/JNEUROSCI.4071-08.2009

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Cellular/Molecular
Localization of the Endocannabinoid-Degrading Enzyme Fatty Acid Amide Hydrolase in Rat Dorsal Root Ganglion Cells and Its Regulation after Peripheral Nerve Injury

Isobel J. Lever,¹ Michelle Robinson,³ Mario Cibelli,² Cleoper Paule,¹ Peter Santha,¹ Louis Yee,¹ Stephen P. Hunt,³ Benjamin F. Cravatt,⁴ Maurice R. Elphick,⁵ Istvan Nagy,¹ and Andrew S. C. Rice¹

¹Pain Research Group and ²Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, United Kingdom, ³Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom, ⁴The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, and ⁵School of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, United Kingdom

Correspondence should be addressed to Prof. Andrew S. C. Rice, Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Road, London SW10 9NH, UK. Email: a.rice{at}imperial.ac.uk

Fatty acid amide hydrolase (FAAH) is a degradative enzyme for a group of endogenous signaling lipids that includes anandamide (AEA). AEA acts as an endocannabinoid and an endovanilloid by activating cannabinoid and vanilloid type 1 transient receptor potential (TRPV1) receptors, respectively, on dorsal root ganglion (DRG) sensory neurons. Inhibition of FAAH activity increases AEA concentrations in nervous tissue and reduces sensory hypersensitivity in animal pain models. Using immunohistochemistry, Western blotting, and reverse transcription-PCR, we demonstrate the location of the FAAH in adult rat DRG, sciatic nerve, and spinal cord. In naive rats, FAAH immunoreactivity localized to the soma of 32.7 ± 0.8% of neurons in L4 and L5 DRG. These were small-sized (mean soma area, 395.96 ± 5.6 µm²) and predominantly colabeled with peripherin and isolectin B4 markers of unmyelinated C-fiber neurons; 68% colabeled with antibodies to TRPV1 (marker of nociceptive DRG neurons), and <2% colabeled with NF200 (marker of large myelinated neurons). FAAH-IR was also present in small, NF200-negative cultured rat DRG neurons. Incubation of these cultures with the FAAH inhibitor URB597 increased AEA-evoked cobalt uptake in a capsazepine-sensitive manner. After sciatic nerve axotomy, there was a rightward shift in the cell-size distribution of FAAH-immunoreactive (IR) DRG neurons ipsilateral to injury: FAAH immunoreactivity was detected in larger-sized cells that colabeled with NF200. An ipsilateral versus contralateral increase in both the size and proportion of FAAH-IR DRG occurred after spinal nerve transection injury but not after chronic inflammation of the rat hindpaw 2 d after injection of complete Freund's adjuvant. This study reveals the location of FAAH in neural tissue involved in peripheral nociceptive transmission.

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Received Aug. 26, 2008; revised Nov. 4, 2008; accepted Jan. 14, 2009.

Correspondence should be addressed to Prof. Andrew S. C. Rice, Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea and Westminster Hospital Campus, 369 Fulham Road, London SW10 9NH, UK. Email: a.rice{at}imperial.ac.uk

This article has been cited by other articles:

				S. G. Kinsey, J. Z. Long, S. T. O'Neal, R. A. Abdullah, J. L. Poklis, D. L. Boger, B. F. Cravatt, and A. H. Lichtman Blockade of Endocannabinoid-Degrading Enzymes Attenuates Neuropathic Pain J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 902 - 910. [Abstract] [Full Text] [PDF]

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