Progress in study of Cannabis sativa leaves extracts without psychotropic cannabinoids in animal model of neuropathic pain

Marcin Ożarowski; Przemysław Ł. Mikolajczak; Anna Bogacz; Joanna Bartkowiak-Wieczorek; Radosław Kujawski; Marian Majchrzycki; Karolina Wielgus; Agnieszka Seremak-Mrozikiewicz; Bogusław Czerny

doi:10.20883/medical.e88

Authors

Marcin Ożarowski Department of Pharmaceutical Botany and Plant Biotechnology, Poznan University of Medical Sciences, Poland Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
Przemysław Ł. Mikolajczak Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland Department of Pharmacology, Poznan University of Medical Sciences, Poland
Anna Bogacz Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
Joanna Bartkowiak-Wieczorek Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
Radosław Kujawski Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
Marian Majchrzycki Department of Reumathology and Rehabilitation, Poznan University of Medical Sciences, Poland
Karolina Wielgus Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
Agnieszka Seremak-Mrozikiewicz Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poland Laboratory of Molecular Biology, Poznan University of Medical Sciences, Poland
Bogusław Czerny Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin, Poland Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland

DOI:

https://doi.org/10.20883/medical.e88

Keywords:

cannabinoids, analgesic effect, animal models

Abstract

Neuropathic pain is a type of chronic pain caused by a lesion or disease of the somatosensory nervous system. Current therapy for this pain includes the use of pharmacological and nonpharmacological methods but due to the fact that a lot of therapy does not produce the analgesic results, it is necessary to search for new and more effective pharmacological strategy in relief of this type of pain. One of the interesting natural sources of compounds against this type of pain is extract of Cannabis sativa without psychotropic cannabinoids. Medicinal properties of C. sativa have been explored for centuries. It is well established that active compounds of this herb act through two cannabinoid receptors (CB1, CB2) as endocannabinoid system in the central nervous system. The present review addresses the recent advances in the study of pharmacological mechanisms on cellular and receptor level underlying non-hallucinogenic cannabinoid analgesic effect. In recent years, results of studies allow to state that special plant extract of C. sativa (without psychotropic cannabinoids) may be a promising source of drug used to relieve neuropathic pain.

Downloads

Download data is not yet available.

References

Culter ED, Furukawa KT. Neuropathic pain: treatment options report. California HealthCare Fundation. 2006;1–29.

Baron R, Andreas B, Gunnar W. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9:807–819.

Bouhassira D, Lante´ri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136:380–387.

Lairda B, Colvinb L, Fallona M. Management of cancer pain: basic principles and neuropathic cancer pain. Eur J Cancer. 2008;44:1078–1082.

Urch CE, Dickenson AH. Neuropathic pain in cancer. Eur J Cancer. 2008;44:1091–1096.

Gondim FAA, Brannagan TH, Sander HW, Chin RL, Latov N. Peripheral neuropathy in patients with inflammatory bowel disease. Brain. 2005;128:867–879.

Attal N, Cruccu G, Baron R, Haanpa M, Hansson P, Jensen TS, Nurmikko T. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17:1113–1123.

Woroń J, Filipczak-Bryniarska I, Dorazil-Dudzik M, Wordliczek J. Bezpieczeństwo pacjenta w farmakoterapii bólu. Ból. 2009;10(3): 47–72.

Yanow J, Pappagallo M, Pillai L. Complex Regional Pain Syndrome (CRPS/RSD) and neuropathic pain: role of intravenous bisphosphonates as analgesics. ScientificWorld Journal. 2008;8:229–236.

Authier N, Balayssac D, Marchand F, Ling B, Zangarelli A, Descoeur J, Coudore F, Bourinet E, Eschalier A. Animal Models of Chemotherapy-Evoked Painful Peripheral Neuropathies. Neurotherapeutics 2009;6:620–629.

Walker JM, Huang SM. Cannabinoid analgesia. Pharmacol Ther. 2002;95:127–135.

Palmer SL, Thakur GA, Makriyannis A. Cannabinergic ligands. Chem Phys Lipids. 2002;121:3–19.

Malek N, Kucharczyk M, Starowicz K. Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain. Biomed Res Int. 2014. Article ID 686908.

Luchicchi A, Pistis M. Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids. Mol Neurobiol. 2012;46:374–392.

Sousa-Valente J, Varga K, Ananthan A, Khajuria A, Nagy I. Anandamide in primary sensory neurons: too much of a good thing? Eur J Neurosci. 2014;39:409–418.

Desroches J, Charron S, Bouchard JF, Beaulieu P. Endocannabinoids decrease neuropathic pain-related behavior in mice through the activation of one or both peripheral CB1 and CB2 receptors. Neuropharmacol. 2014;77:441–452.

Pertwee RG. The Therapeutic Potential of Drugs That Target Cannabinoid Receptors or Modulate the Tissue Levels or Actions of Endocannabinoids. AAPS J. 2005;7:625–654.

Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M. CB1-cannabinoid and mu-opioid receptor colocalization on postsynaptictarget in the rat dorsal horn. Neuroreport. 2001;12:3689–3692.

Rodriguez JJ, Mackie K, Pickel VM. Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat Caudate putamen nucleus. J Neurosci. 2001;21:823–833.

Gifford AN, Makriyannis A, Volkow ND. Gatley SJ. In vivo imaging of the brain cannabinoid receptor. Chem Phys Lipids. 2002;121:65–72.

Lichtman AH, Cook SA, Martin BR. Investigation of brain sites mediating cannabinoid-induced antinociception in evidence supporting periaqueductal gray involvement. J Pharmacol Exp Ther. 1996;276:585–593.

Hohmann AG. Spinal and peripheral mechanisms of cannabinoid antinociception: behavioral, neurophysiological and neuroanatomical perspectives. Chem Phys Lipids. 2002;121:173–190.

Vigano D, Rubino T, Parolaro D. Molecular and cellular basis of cannabinoid and opioid interactions. Pharmacol Biochem Behav. 2005;81:360–368.

Manzanares J, Corchero J, Romero J, Fernandez-Ruiz JJ, Ramos A, Fuentes JA. Pharmacological and biochemical interactions between opioids and cannabinoids. Trends Pharmacol Sci. 1999;20:287–294.

Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63:569–611.

Valenzano KJ, Tafessem L, Lee G, Harrison JE, Bouletm JM, Gottshallm SL. Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacol. 2005;48:658–672.

Palazzo E, Luongo Lo, de Novellis V, Rossi F, Maione S. The role of cannabinoid receptors in the descending modulation of pain. Pharmaceuticals. 2010;3:2661–2673.

Leung L, Cahill CM. TNF-alpha and neuropathic pain – a review. J Neuroinflammation. 2010;16:7–27.

Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51: 240–264.

Machelska H. Dual peripheral actions of immune cells in neuropathic pain. Arch Immunol Ther Exp (Warsz). 2011;59:11–24.

Jaggi AS, Singh N. Differential effect of spironolactone in chronic constriction injury and vincristine-induced neuropathic pain NPin rats. Eur J Pharmacol. 2010;648: 102–109.

Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov. 2004;3:17–26.

Yamamoto Y, Gaynor RB. IkappaB kinases: key regulators of the NF-kappaB pathway. Trends Biochem Sci. 2004;29:72–79.

Ledeboer A, Gamanos M, Martin D, Maier SF, Watkins LR, Quan N. Involvement of spinal cord nuclear factor kappaB activation in rat models of proinflammatory cytokine-mediated pain facilitation. Eur J Neurosci. 2005;22:1977–1986.

Kaltschmidt B, Uherek M, Wellmann H, Volk B, Kaltschmidt C. Inhibition of NF-kappaB potentiates amyloid betamediated neuronal apoptosis. Proc Natl Acad Sci USA. 1999;96:9409–9414.

Ma W, Bisby MA. Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries. Brain Res. 1998;797:243–254.

Mattson MP, Camandola S. NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest. 2001;107:247–254.

Bethea JR, Castro M, Keane RW, Lee TT, Dietrich WD, Yezierski RP. Traumatic spinal cord injury induces nuclear factor-kappaB activation. J Neurosci. 1998;18: 3251–3260.

Niederberger E, Kühlein H, Geisslinger G. Update on the pathobiology of neuropathic pain. Expert Rev Proteomics. 2008;5:799–818.

Niederberger E, Geisslinger G. The IKK-NF-{kappa}B pathway: a source for novel molecular drug targets in pain therapy? The FASEB Journal. 2008;22:3432–3442.

Reuter U, Chiarugi A, Bolay H, Moskowitz MA. Nuclear factor-kappaB as a molecular target for migraine therapy. Ann. Neurol. 2002;51:507–516.

Sarchielli P, Floridi A, Mancini ML, Rossi C, Coppola F, Baldi A, Pini LA, Calabresi P. NF-kappaB activity and iNOS expression in monocytes from internal jugular blood of migraine without aura patients during attacks. Cephalalgia. 2006;26:1071–1079.

Wu LC, Goettl VM, Madiai F, Hackshaw KV, Hussain SR. Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury. BMC Neurosci. 2006;7:4.

Zhang YP, Fu Es, Sagen J, Levitt RC, Candiotti KA, Bethea JR, Brambilla R. Glial NF-kappa B inhibition alters neuropeptide expression after sciatic nerve injury in mice. Brain Res. 2011;1385:38–46.

Fu ES, Zhang YP, Sagen J, Candiotti KA, Morton PD, Liebl DJ, Bethea JR, Brambilla R. Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury. Pain. 2010;148:509–518.

Wu LJ, Zhuo M. Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. Neurotherapeutics. 2009;6:693–702.

Tian Y, Wang S, Ma Y, Lim G, Kim H, Mao J. Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain. Pain. 2011;152:1263–1271.

Richardson JD, Aanonsen L, Hargreaves KM. Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia. J Neurosci. 1998;8:451–457.

Kauppila T. Correlation between autotomy-behavior and current theories of neuropathic pain. Neurosci Biobehav Rev. 1998;23:111–129.

Collins S, Sigtermans MJ, Dahan A, Zuurmond WW, Perez RS. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Medicine. 2010;11:1726–1742.

Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Cell press. Trends Pharmacol Sci. 2009;30:515–527.

Mechoulam R. The pharmacohistory of Cannabis sativa. In: Mechoulam R (ed.). Cannabinoids as therapeutic agents. Boca Raton; CRC; 1986.

Razdan RK. Structure activity relationships in cannabinoids. Pharmacol Rev. 1986;38:75–149.

Gardner EL. Addictive potential of cannabinoids: the underlying neurobiology. Chem Phys Lipids. 2002;121:267–290.

Razdan RK, Mahadevan A. Recent advances in the synthesis of endocannabinoid related ligands. Chem Phys Lipids. 2002;121:21–33.

Mechoulam R, Hanus L. Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chem Phys Lipids. 2002;121:35–43.

Gertsch J, Pertwee RG, Di Marzo V. Phytocannabinoids beyond the Cannabis plant – do they exist? Br J Pharmacol. 2010;160(3):523–529.

Fischedick JT, Hazekamp A, Erkelens T, Choi YH, Verpoorte R. Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. Phytochem. 2010;71:2058–2073.

Fetterman PS, Keith ES, Waller CW, Guerrero O, Doorenbos NJ, Quimby MW. Mississippi-grown Cannabis sativa L. preliminary observation on chemical definition of phenotype and variations in tetrahydrocannabinol content versus age, sex, and plant part. J Pharm Sci. 1971;60:1246–1277.

Thomas A, Stevenson LA, Wease KN, Price MR, Baillie G, Ross RA, Pertwee RG. Evidence that the plant cannabinoid D9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br J Pharmacol. 2005;146:917–926.

Bolognini D, Costa B, Maione S, Comelli F, Marini P, Di Marzo V, et al. The plant cannabinoid delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br J Pharmacol. 2010;160:677–687.

Malan TP, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F. Inhibition of pain responses by activation of CB2 cannabinoid receptors. Chem Phys Lipids. 2002;121:191–200.

Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M, Zimmer A. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci USA. 2008;105:9099–9104.

Bento AF, Marcon R, Dutra RC, Claudino RF, Cola M, Leite DF, Calixto JB. ß-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPAR? pathway. Am J Pathol. 2011;178: 1153–1166.

Klauke AL, Racz I, Pradier B, Markert A, Zimmera AM, Gertsch J, Zimmer A. The cannabinoidCB2 receptor-selective phytocannabinoidbeta-caryophylleneexerts analgesic effectsinmousemodelsof inflammatory andneuropathicpain. Eur Neuropsychopharmacol. 2014;24:608–620.

Zuardi AW, Crippa JAS, Hallak JEC, Moreira FA, Guimaraes FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006;39:421–429.

Campos AC, Guimaraes FS. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacol (Berl). 2008;199:223–230.

Evans FJ. Cannabinoids: the separation of central from peripheral effects on a structural basis. Planta Med. 1991;57(Suppl.):60–67.

Formukong EA, Evans AT, Evans FJ. Analgesic and anti-inflammatory activity of constituents of Cannabis sativa L. Inflammation. 1988;12:361–371.

Sanders J, Jackson DM, Starmer GA. Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse. Psychopharmacol (Berl.) 1979;61:281–285.

Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007;556:75–83.

Costa B, Colleoni M, Conti S, Parolaro D, Franke C, Trovato AE, Giagnoni G. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn-Schmiedeberg’s Arch Pharmacol. 2004;369:294–299.

Zurier RB. Prospects for Cannabinoids as Anti-inflammatory Agents. J Cell Biochem. 2003;88:462–466.

Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006; 39:143–151.

Toth CC, Jedrzejewski NM, Ellis CL, Frey WH. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Molecular Pain. 2010;6:16.

Zajicek JP, Apostu V. Role of cannabinoids in multiple sclerosis. CNS Drugs. 2011;25:187–201.

Grotenhermen F. Cannabinoids in cancer pain. Cannabinoids. 2010;5:1–3.

Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013;260:984–997.

Robson P. Abuse potential and psychoactive effects of ?-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Expert Opin Drug Saf. 2011;10:675–685.

Fine PG, Rosenfeld MJ. Cannabinoids for neuropathic pain. Curr Pain Headache Rep. 2014;18:451.