Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment

Guindon, Josée; Lai, Yvonne; Takacs, Sara M.; Bradshaw, Heather B.; Hohmann, Andrea G.

doi:10.1016/j.phrs.2012.10.013

Cited by 160Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsCancer Treatment and Pharmacology

Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment

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Guindon, Josée, Lai, Yvonne, Takacs, Sara M., Bradshaw, Heather B., Hohmann, Andrea G.·2013·Pharmacological Research

DOI 10.1016/j.phrs.2012.10.013PMC PMC3525790

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Abstract

Cisplatin, a platinum-derived chemotherapeutic agent, produces mechanical and coldallodynia reminiscent of chemotherapy-induced neuropathy in humans. The endocannabinoid system represents a novel target for analgesic drug development. The endocannabinoid signaling system consists of endocannabinoids (e.g. anandamide (AEA) and 2-arachidonoylglycerol (2-AG)), cannabinoid receptors (e.g. CB(1) and CB(2)) and the enzymes controlling endocannabinoid synthesis and degradation. AEA is hydrolyzed by fatty-acid amide hydrolase (FAAH) whereas 2-AG is hydrolyzed primarily by monoacylglycerol lipase (MGL). We compared effects of brain permeant (URB597) and impermeant (URB937) inhibitors of FAAH with an irreversible inhibitor of MGL (JZL184) on cisplatin-evoked behavioral hypersensitivities. Endocannabinoid modulators were compared with agents used clinically to treat neuropathy (i.e. the opioid analgesic morphine, the anticonvulsant gabapentin and the tricyclic antidepressant amitriptyline). Cisplatin produced robust mechanical and cold allodynia but did not alter responsiveness to heat. After neuropathy was fully established, groups received acute intraperitoneal (i.p.) injections of vehicle, amitriptyline (30 mg/kg), gabapentin (100 mg/kg), morphine (6 mg/kg), URB597 (0.1 or 1 mg/kg), URB937 (0.1 or 1 mg/kg) or JZL184 (1, 3 or 8 mg/kg). Pharmacological specificity was assessed by coadministering each endocannabinoid modulator with either a CB(1) (AM251 3 mg/kg), CB(2) (AM630 3 mg/kg), TRPV1 (AMG9810 3 mg/kg) or TRPA1 (HC030031 8 mg/kg) antagonist. Effects of cisplatin on endocannabinoid levels and transcription of receptors (CB(1), CB(2), TRPV1, TRPA1) and enzymes (FAAH, MGL) linked to the endocannabinoid system were also assessed. URB597, URB937, JZL184 and morphine reversed cisplatin-evoked mechanical and cold allodynia to pre-cisplatin levels. By contrast, gabapentin only partially reversed the observed allodynia while amitriptyline, administered acutely, was ineffective. CB(1) or CB(2) antagonists completely blocked the anti-allodynic effects of both FAAH (URB597, URB937) and MGL (JZL184) inhibitors to mechanical and cold stimulation. By contrast, the TRPV1 antagonist AMG9810 blocked the anti-allodynic efficacy of both FAAH inhibitors, but not the MGL inhibitor. By contrast, the TRPA1 antagonist HC30031 did not attenuate anti-allodynic efficacy of any endocannabinoid modulator. When the levels of endocannabinoids were examined, cisplatin increased both anandamide (AEA) and 2-arachidonoylglycerol (2-AG) levels in the lumbar spinal cord and decreased 2-AG levels (but not AEA) in dorsal hind paw skin. RT-PCR showed that mRNA for FAAH, but not other markers, was upregulated by cisplatin treatment in lumbar spinal cord. The present studies demonstrate that cisplatin alters endocannabinoid tone and that inhibition of endocannabinoid hydrolysis alleviates chemotherapy-induced mechanical and cold allodynia. The anti-allodynic effects of FAAH and MGL inhibitors are mediated by CB(1) and CB(2) cannabinoid receptors, whereas TRPV1, but not TRPA1, -dependent mechanisms contribute to the anti-allodynic efficacy of FAAH (but not MGL) inhibitors. Strikingly, endocannabinoid modulators potently suppressed cisplatin-evoked allodynia with a rapid onset and showed efficacy that equaled or exceeded that of major classes of anti-neuropathic pain medications used clinically. Thus, inhibition of endocannabinoid hydrolysis, via FAAH or MGL inhibitors, represents an efficacious pharmacological approach for suppressing chemotherapy-induced neuropathic pain.

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FAAH and MAGL inhibitors reduced cisplatin-induced mechanical and cold allodynia, which are CB1 and CB2 receptors-mediated.
“Finally, FAAH and MAGL inhibitors reduced cisplatin-induced mechanical and cold allodynia, which are CB 1 and CB 2 receptors-mediated (Guindon et al, 2013;Khasabova et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Guindon et al, 2013

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The Blockade of the Transient Receptor Potential Vanilloid Type 1 and Fatty Acid Amide Hydrolase Decreases Symptoms and Central Sequelae in the Medial Prefrontal Cortex of Neuropathic Rats
de Novellis, V., Vita, D., Gatta, L., Luongo, L., Bellini, G., De Chiaro, M., Marabese, I., Siniscalco, D., Boccella, S., Piscitelli, F., et al. (2011) · Molecular Pain · doi:10.1186/1744-8069-7-7 · Cited by 90 · see citing works
Mechanical Allodynia Induced by Paclitaxel, Oxaliplatin and Vincristine: Different Effectiveness of Gabapentin and Different Expression of Voltage-Dependent Calcium Channel .ALPHA.2.DELTA.-1 Subunit
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MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models
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Spinal anandamide produces analgesia in neuropathic rats: Possible CB1- and TRPV1-mediated mechanisms
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WIN 55,212-2 prevents mechanical allodynia but not alterations in feeding behaviour induced by chronic cisplatin in the rat
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Modulation of the anti‐nociceptive effects of 2‐arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model
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Pathophysiology and Animal Models of Cancer-Related Painful Peripheral Neuropathy
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Altered feeding behaviour induced by long-term cisplatin in rats
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Experimental Studies of Potential Analgesics for the Treatment of Chemotherapy-Evoked Painful Peripheral Neuropathies
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Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms
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Pharmacological Characterization of a Novel Cannabinoid Ligand, MDA19, for Treatment of Neuropathic Pain
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The analgesic effect of N-arachidonoyl-serotonin, a FAAH inhibitor and TRPV1 receptor antagonist, associated with changes in rostral ventromedial medulla and locus coeruleus cell activity in rats
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Combination of ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, and cisplatin enhances the inhibition of growth of human ovarian cancers
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Gabapentin for Relief of Neuropathic Pain Related to Anticancer Treatment: A Preliminary Study
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Evidence for an antihyperalgesic effect of venlafaxine in vincristine-induced neuropathy in rat
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Hematology - Oncology Therapy
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Antinociceptive Effects of Racemic AM1241 and Its Chirally Synthesized Enantiomers: Lack of Dependence upon Opioid Receptor Activation
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Pharmacokinetics of Amitriptyline and One of Its Metabolites, Nortriptyline, in Rats: Little Contribution of Considerable Hepatic First-Pass Effect to Low Bioavailability of Amitriptyline Due to Great Intestinal First-Pass Effect
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Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain
Sisignano, M., Baron, R., Scholich, K., & Geißlinger, G. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.211 · Cited by 340 · see citing works
Chemical Probes of Endocannabinoid Metabolism
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The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain
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A Double-Blind, Placebo-Controlled, Crossover Pilot Trial With Extension Using an Oral Mucosal Cannabinoid Extract for Treatment of Chemotherapy-Induced Neuropathic Pain
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Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies
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The Role of the Endocannabinoid System in Pain
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Mechanisms Involved in the Development of Chemotherapy-Induced Neuropathy
Boyette-Davis, J. A., Walters, E. T., & Dougherty, P. M. (2015) · Pain Management · doi:10.2217/pmt.15.19 · Cited by 168 · see citing works
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Positive Allosteric Modulation of Cannabinoid Receptor Type 1 Suppresses Pathological Pain Without Producing Tolerance or Dependence
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In vivo characterization of the highly selective monoacylglycerol lipase inhibitor <scp>KML</scp>29: antinociceptive activity without cannabimimetic side effects
Ignatowska‐Jankowska, B. M., Ghosh, S., Crowe, M. S., Kinsey, S. G., Niphakis, M. J., Abdullah, R. A., Tao, Q., O' Neal, S. T., Walentiny, D. M., Wiley, J. L., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12298 · Cited by 128 · see citing works
Thermo-Sensitive TRP Channels: Novel Targets for Treating Chemotherapy-Induced Peripheral Pain
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Neuroendocrinology and neurobiology of sebaceous glands
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Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Therapeutic Avenues
Bae, E. H., Greenwald, M. K., & Schwartz, A. G. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01142-2 · Cited by 125 · see citing works
An Updated Understanding of the Mechanisms Involved in cHemotherapy-Induced Neuropathy
Boyette-Davis, J. A., Hou, S., Abdi, S., & Dougherty, P. M. (2018) · Pain Management · doi:10.2217/pmt-2018-0020 · Cited by 95 · see citing works
Antineuropathic Profile of N-Palmitoylethanolamine in a Rat Model of Oxaliplatin-Induced Neurotoxicity
Mannelli, L. D. C., Pacini, A., Corti, F., Boccella, S., Luongo, L., Esposito, E., Cuzzocrea, S., Maione, S., Calignano, A., & Ghelardini, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128080 · Cited by 91 · see citing works
Selective Monoacylglycerol Lipase Inhibitors: Antinociceptive versus Cannabimimetic Effects in Mice
Ignatowska-Jankowska, B. M., Wilkerson, J. L., Mustafa, M. A., Abdullah, R. A., Niphakis, M. J., Wiley, J. L., Cravatt, B. F., & Lichtman, A. H. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.222315 · Cited by 89 · see citing works
Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research
Leitzelar, B. N., & Koltyn, K. F. (2021) · Sports Medicine - Open · doi:10.1186/s40798-021-00307-9 · Cited by 84 · see citing works
The endocannabinoid hydrolysis inhibitor SA-57: intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice
Wilkerson, J. L., Ghosh, S., Mustafa, M., Abdullah, R. A., Niphakis, M. J., Cabrera, R., Maldonado, R. L., Cravatt, B. F., & Lichtman, A. H. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.11.015 · Cited by 78 · see citing works
Monoacylglycerol Lipase Inhibitors Reverse Paclitaxel-Induced Nociceptive Behavior and Proinflammatory Markers in a Mouse Model of Chemotherapy-Induced Neuropathy
Curry, Z. A., Wilkerson, J. L., Bağdaş, D., Kyte, S. L., Patel, N. H., Donvito, G., Mustafa, M. A., Poklis, J. L., Niphakis, M. J., Hsu, K., et al. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.117.245704 · Cited by 78 · see citing works
Endocannabinoid-Based Therapies
Piomelli, D., & Tagne, A. M. (2021) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-052220-021800 · Cited by 77 · see citing works
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Selenium potentiates the anticancer effect of cisplatin against oxidative stress and calcium ion signaling-induced intracellular toxicity in MCF-7 breast cancer cells: involvement of the TRPV1 channel
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Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis
Wen, J., Ribeiro, R., Tanaka, M., & Zhang, Y. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.010 · Cited by 74 · see citing works
Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain
Blanton, H. L., Brelsfoard, J., Deturk, N., Pruitt, K., Narasimhan, M., Morgan, D. J., & Guindon, J. (2019) · Drugs · doi:10.1007/s40265-019-01132-x · Cited by 70 · see citing works
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Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice
Harris, H., Sufka, K., Gul, W., & ElSohly, M. (2016) · Planta Medica · doi:10.1055/s-0042-106303 · Cited by 69 · see citing works
The Selective Monoacylglycerol Lipase Inhibitor MJN110 Produces Opioid-Sparing Effects in a Mouse Neuropathic Pain Model
Wilkerson, J. L., Niphakis, M. J., Grim, T. W., Mustafa, M. A., Abdullah, R. A., Poklis, J. L., Dewey, W. L., Akbarali, H. I., Banks, M. L., Wise, L. E., et al. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.229971 · Cited by 67 · see citing works
Monoglyceride lipase: Structure and inhibitors
Scalvini, L., Piomelli, D., & Mor, M. (2015) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2015.07.011 · Cited by 66 · see citing works
A Lipid Gate for the Peripheral Control of Pain
Piomelli, D., Hohmann, A. G., Seybold, V. S., & Hammock, B. D. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3475-14.2014 · Cited by 65 · see citing works
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Prophylactic Cannabinoid Administration Blocks the Development of Paclitaxel-Induced Neuropathic Nociception during Analgesic Treatment and following Cessation of Drug Delivery
Rahn, E. J., Deng, L., Thakur, G. A., Vemuri, K. V., Zvonok, A. M., Lai, Y. Y., Makriyannis, A., & Hohmann, A. G. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-27 · Cited by 65 · see citing works
Self-citation
Small molecule inhibitors of PSD95-nNOS protein–protein interactions as novel analgesics
Lee, W.-H., Xu, Z., Ashpole, N. M., Hudmon, A., Kulkarni, P. M., Thakur, G. A., Lai, Y. Y., & Hohmann, A. G. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.05.038 · Cited by 66 · see citing works
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Optimization of a Cisplatin Model of Chemotherapy-Induced Peripheral Neuropathy in Mice: Use of Vitamin C and Sodium Bicarbonate Pretreatments to Reduce Nephrotoxicity and Improve Animal Health Status
Guindon, J., Deng, L., Fan, B., Wager‐Miller, J., & Hohmann, A. G. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-56 · Cited by 62 · see citing works
Self-citation
Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation
Mulpuri, Y., Marty, V. N., Munier, J. J., Mackie, K., Schmidt, B. L., Seltzman, H. H., & Spigelman, I. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.07.002 · Cited by 62 · see citing works
Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment
Campos, R. M. P., Aguiar, A. F. L., Paes-Colli, Y., Trindade, P. M. P., Ferreira, B. K., Reis, R. A. D. M., & Sampaio, L. D. S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.785176 · Cited by 59 · see citing works
Targeting the cannabinoid system for pain relief?
Chiou, L., Hu, S. S., & Ho, Y. (2013) · Acta anaesthesiologica Taiwanica · doi:10.1016/j.aat.2013.10.004 · Cited by 57 · see citing works
Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice
Ghosh, S., Kinsey, S. G., Liu, Q.-S., Hruba, L., McMahon, L. R., Grim, T. W., Merritt, C. R., Wise, L. E., Abdullah, R. A., Selley, D. E., et al. (2015) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.222851 · Cited by 54 · see citing works
Diacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain
Wilkerson, J. L., Ghosh, S., Bağdaş, D., Mason, B. L., Crowe, M. S., Hsu, K., Wise, L. E., Kinsey, S. G., Damaj, M. I., Cravatt, B. F., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13469 · Cited by 55 · see citing works
Dual-Acting Compounds Targeting Endocannabinoid and Endovanilloid Systems—A Novel Treatment Option for Chronic Pain Management
Małek, N., & Starowicz, K. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00257 · Cited by 51 · see citing works
Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain
Hossain, M. Z., Ando, H., Unno, S., & Kitagawa, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041423 · Cited by 52 · see citing works
JZL184 is anti-hyperalgesic in a murine model of cisplatin-induced peripheral neuropathy
Khasabova, I. A., Yao, X., Paz, J., Lewandowski, C. T., Lindberg, A. E., Coicou, L., Burlakova, N., Simone, D. A., & Seybold, V. S. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.09.008 · Cited by 50 · see citing works
The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system
Mengmeng, Z., Zhang, Q., Huo, M., Song, H., Chang, H., Cao, J., Fang, Y., & Zhang, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114516 · Cited by 50 · see citing works
Update on the Role of Spinal Cord TRPV1 Receptors in Pain Modulation
Spicarova, D., Nerandžič, V., & Paleček, J. (2014) · Physiological Research · doi:10.33549/physiolres.932713 · Cited by 50 · see citing works
Chronic stress‐induced mechanical hyperalgesia is controlled by capsaicin‐sensitive neurones in the mouse
Scheich, B., Vincze, P., Szőke, É., Borbély, É., Hunyady, Á., Szolcsányi, J., Dénes, Á., Környei, Z., Gaszner, B., & Helyes, Z. (2017) · European Journal of Pain · doi:10.1002/ejp.1043 · Cited by 48 · see citing works
Cannabinoids in the descending pain modulatory circuit: Role in inflammation
Bouchet, C. A., & Ingram, S. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107495 · Cited by 51 · see citing works
The effect of FAAH , MAGL , and Dual FAAH / MAGL inhibition on inflammatory and colorectal distension‐induced visceral pain models in Rodents
Sakın, Y. S., Dogrul, A. B., İlkaya, F., Seyrek, M., Ulaş, Ü. H., Gülşen, M., & Bagci, S. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12563 · Cited by 47 · see citing works
Chemotherapy-induced painful neuropathy
Hopkins, H. L., Duggett, N. A., & Flatters, S. J. L. (2016) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000204 · Cited by 47 · see citing works
Tempol Ameliorates and Prevents Mechanical Hyperalgesia in a Rat Model of Chemotherapy-Induced Neuropathic Pain
Kim, H. K., Hwang, S.-H., & Abdi, S. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00532 · Cited by 46 · see citing works
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Authors: Guindon, J., Lai, Y., Takacs, S. M., Bradshaw, H. B., & Hohmann, A. G.
Affiliations: Indiana University Bloomington (US)
Corresponding author: Guindon, Josée
Hohmann, Andrea G.
ORCID: Guindon, Josée
Takacs, Sara M.
Bradshaw, Heather B.
Hohmann, Andrea G.
Venue: Pharmacological Research
Publisher: Elsevier BV
Published: 2013-01
Volume: 67
Issue: 1
Pages: 94-109
ISSN: 1043-6618 (ISSN-L)
DOI: 10.1016/j.phrs.2012.10.013
PMC: PMC3525790
OpenAlex: W2008749179
Cited by: 160
References: 100
Citations by year: 2026: 2 · 2025: 12 · 2024: 8 · 2023: 7 · 2022: 11 · 2021: 18 · 2020: 12 · 2019: 8 · 2018: 15 · 2017: 11 · 2016: 9 · 2015: 18 · 2014: 20 · 2013: 9
FWCI: 11.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacological Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (DA028200, R01DA021644, RC1DA028200, R21DA032150, DA021644)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords: endocannabinoid system, chemotherapy-induced peripheral neuropathy, cisplatin, fatty acid amide hydrolase, monoacylglycerol lipase, URB597, JZL184, anandamide, 2-arachidonoylglycerol, allodynia, mechanical hypersensitivity, cold allodynia, cannabinoid receptors, TRPV1, TRPA1, amitriptyline, gabapentin, morphine
MeSH terms: Fatty Acid Amide Hydrolases, Amidohydrolases, Analgesics, Animals, Antineoplastic Agents, Arachidonic Acids, Benzamides, Cannabinoids, Carbamates, Cisplatin, Enzyme Inhibitors, Ganglia, Spinal, Glycerides, Hyperalgesia, Male, Monoacylglycerol Lipases, Peripheral Nervous System Diseases, Piperidines, RNA, Messenger, Spinal Cord, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Lipid Metabolism, TRPV Cation Channels, Rats, Benzodioxoles, Polyunsaturated Alkamides, Endocannabinoids

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Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment

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